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Volume 51 Issue 2
Feb.  2024
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Article Contents

Exploring noncoding variants in genetic diseases: from detection to functional insights

doi: 10.1016/j.jgg.2024.01.001
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This work was supported by the National Key Research and Development Program of China (82030030) and the 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC20002) to H. Yuan, Sichuan Science and Technology Program (2022YFS0211) to K. Wu.

  • Received Date: 2023-11-05
  • Accepted Date: 2024-01-01
  • Rev Recd Date: 2023-12-26
  • Available Online: 2025-06-07
  • Publish Date: 2024-01-04
  • Previous studies on genetic diseases predominantly focused on protein-coding variations, overlooking the vast noncoding regions in the human genome. The development of high-throughput sequencing technologies and functional genomics tools has enabled the systematic identification of functional noncoding variants. These variants can impact gene expression, regulation, and chromatin conformation, thereby contributing to disease pathogenesis. Understanding the mechanisms that underlie the impact of noncoding variants on genetic diseases is indispensable for the development of precisely targeted therapies and the implementation of personalized medicine strategies. The intricacies of noncoding regions introduce a multitude of challenges and research opportunities. In this review, we introduce a spectrum of noncoding variants involved in genetic diseases, along with research strategies and advanced technologies for their precise identification and in-depth understanding of the complexity of the noncoding genome. We will delve into the research challenges and propose potential solutions for unraveling the genetic basis of rare and complex diseases.
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  • Aida, T., Feng, G., 2020. The dawn of non-human primate models for neurodevelopmental disorders. Curr. Opin. Genet. Dev. 65, 160-168.
    Allesoe, R.L., Lundgaard, A.T., Hernandez Medina, R., Aguayo-Orozco, A., Johansen, J., Nissen, J.N., Brorsson, C., Mazzoni, G., Niu, L., Biel, J.H., et al., 2023. Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models. Nat. Biotechnol. 41, 399-408.
    Allou, L., Balzano, S., Magg, A., Quinodoz, M., Royer-Bertrand, B., Schopflin, R., Chan, W.L., Speck-Martins, C.E., Carvalho, D.R., Farage, L., et al., 2021. Non-coding deletions identify Maenli lncRNA as a limb-specific En1 regulator. Nature 592, 93-98.
    Alvarez, R.V., Li, S., Landsman, D., Ovcharenko, I., 2018. SNPDelScore: combining multiple methods to score deleterious effects of noncoding mutations in the human genome. Bioinformatics 34, 289-291.
    Amiri, A., Coppola, G., Scuderi, S., Wu, F., Roychowdhury, T., Liu, F., Pochareddy, S., Shin, Y., Safi, A., Song, L., et al., 2018. Transcriptome and epigenome landscape of human cortical development modeled in organoids. Science 362, eaat6720.
    Anderson, D.M., Anderson, K.M., Chang, C.L., Makarewich, C.A., Nelson, B.R., McAnally, J.R., Kasaragod, P., Shelton, J.M., Liou, J., Bassel-Duby, R., et al., 2015. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell 160, 595-606.
    Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., Suzuki, T., et al., 2014. An atlas of active enhancers across human cell types and tissues. Nature 507, 455-461.
    Ang, C.E., Ma, Q., Wapinski, O.L., Fan, S., Flynn, R.A., Lee, Q.Y., Coe, B., Onoguchi, M., Olmos, V.H., Do, B.T., et al., 2019. The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders. Elife 8, e41770.
    Anna, A., Monika, G., 2018. Splicing mutations in human genetic disorders: examples, detection, and confirmation. J. Appl. Genet. 59, 253-268.
    Arnold, C.D., Gerlach, D., Stelzer, C., Boryn, L.M., Rath, M., Stark, A., 2013. Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 339, 1074-1077.
    Bandiera, S., Hatem, E., Lyonnet, S., Henrion-Caude, A., 2010. microRNAs in diseases: from candidate to modifier genes. Clin. Genet. 77, 306-313.
    Barish, S., Senturk, M., Schoch, K., Minogue, A.L., Lopergolo, D., Fallerini, C., Harland, J., Seemann, J.H., Stong, N., Kranz, P.G., et al., 2022. The microRNA processor DROSHA is a candidate gene for a severe progressive neurological disorder. Hum. Mol. Genet. 31, 2934-2950.
    Bartel, D.P., 2009. MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233.
    Baysoy, A., Bai, Z., Satija, R., Fan, R., 2023. The technological landscape and applications of single-cell multi-omics. Nat. Rev. Mol. Cell Biol. 24, 695-713.
    Beermann, J., Piccoli, M.T., Viereck, J., Thum, T., 2016. Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol. Rev. 96, 1297-1325.
    Beesley, J., Sivakumaran, H., Moradi Marjaneh, M., Lima, L.G., Hillman, K.M., Kaufmann, S., Tuano, N., Hussein, N., Ham, S., Mukhopadhyay, P., et al., 2020. Chromatin interactome mapping at 139 independent breast cancer risk signals. Genome Biol. 21, 8.
    Ben-David, U., Ha, G., Tseng, Y.-Y., Greenwald, N.F., Oh, C., Shih, J., McFarland, J.M., Wong, B., Boehm, J.S., Beroukhim, R., et al., 2017. Patient-derived xenografts undergo mouse-specific tumor evolution. Nat. Genet. 49, 1567-1575.
    Bendl, J., Musil, M., Stourac, J., Zendulka, J., Damborsky, J., Brezovsky, J., 2016. PredictSNP2: a unified platform for accurately evaluating SNP effects by exploiting the different characteristics of variants in distinct genomic regions. PLoS Comput. Biol. 12, e1004962.
    Benner, C., Spencer, C.C., Havulinna, A.S., Salomaa, V., Ripatti, S., Pirinen, M., 2016. FINEMAP: efficient variable selection using summary data from genome-wide association studies. Bioinformatics 32, 1493-1501.
    Bernstein, B.E., Stamatoyannopoulos, J.A., Costello, J.F., Ren, B., Milosavljevic, A., Meissner, A., Kellis, M., Marra, M.A., Beaudet, A.L., Ecker, J.R., et al., 2010. The NIH roadmap epigenomics mapping consortium. Nat. Biotechnol. 28, 1045-1048.
    Bhatia, S., Bengani, H., Fish, M., Brown, A., Divizia, M.T., de Marco, R., Damante, G., Grainger, R., van Heyningen, V., Kleinjan, D.A., 2013. Disruption of autoregulatory feedback by a mutation in a remote, ultraconserved PAX6 enhancer causes aniridia. Am. J. Hum. Genet. 93, 1126-1134.
    Bhatia, S.N., Ingber, D.E., 2014. Microfluidic organs-on-chips. Nat. Biotechnol. 32, 760-772.
    Boissel, S., Reish, O., Proulx, K., Kawagoe-Takaki, H., Sedgwick, B., Yeo, G.S., Meyre, D., Golzio, C., Molinari, F., Kadhom, N., et al., 2009. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am. J. Hum. Genet. 85, 106-111.
    Bonev, B., Cavalli, G., 2016. Organization and function of the 3D genome. Nat. Rev. Genet. 17, 661-678.
    Boyle, A.P., Davis, S., Shulha, H.P., Meltzer, P., Margulies, E.H., Weng, Z., Furey, T.S., Crawford, G.E., 2008. High-resolution mapping and characterization of open chromatin across the genome. Cell 132, 311-322.
    Boyle, A.P., Hong, E.L., Hariharan, M., Cheng, Y., Schaub, M.A., Kasowski, M., Karczewski, K.J., Park, J., Hitz, B.C., Weng, S., et al., 2012. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 22, 1790-1797.
    Bryant, L., Li, D., Cox, S.G., Marchione, D., Joiner, E.F., Wilson, K., Janssen, K., Lee, P., March, M.E., Nair, D., et al., 2020. Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients. Sci. Adv. 6, eabc9207.
    Buenrostro, J.D., Giresi, P.G., Zaba, L.C., Chang, H.Y., Greenleaf, W.J., 2013. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213-1218.
    Buenrostro, J.D., Wu, B., Litzenburger, U.M., Ruff, D., Gonzales, M.L., Snyder, M.P., Chang, H.Y., Greenleaf, W.J., 2015. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature 523, 486-490.
    Calderon, L., Weiss, F.D., Beagan, J.A., Oliveira, M.S., Georgieva, R., Wang, Y.F., Carroll, T.S., Dharmalingam, G., Gong, W., Tossell, K., et al., 2022. Cohesin-dependence of neuronal gene expression relates to chromatin loop length. Elife 11, e76539.
    Calvo, S.E., Pagliarini, D.J., Mootha, V.K., 2009. Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proc. Natl. Acad. Sci. U. S. A. 106, 7507-7512.
    Canver, M.C., Smith, E.C., Sher, F., Pinello, L., Sanjana, N.E., Shalem, O., Chen, D.D., Schupp, P.G., Vinjamur, D.S., Garcia, S.P., et al., 2015. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature 527, 192-197.
    Cartegni, L., Krainer, A.R., 2002. Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1. Nat. Genet. 30, 377-384.
    Cazzola, M., Skoda, R.C., 2000. Translational pathophysiology: a novel molecular mechanism of human disease. Blood 95, 3280-3288.
    Chan, T.L., Yuen, S.T., Kong, C.K., Chan, Y.W., Chan, A.S., Ng, W.F., Tsui, W.Y., Lo, M.W., Tam, W.Y., Li, V.S., et al., 2006. Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer. Nat. Genet. 38, 1178-1183.
    Chen, H.I., Jagadeesh, K.A., Birgmeier, J., Wenger, A.M., Guturu, H., Schelley, S., Bernstein, J.A., Bejerano, G., 2018. An MTF1 binding site disrupted by a homozygous variant in the promoter of ATP7B likely causes Wilson Disease. Eur. J. Hum. Genet. 26, 1810-1818.
    Chen, L., Ge, B., Casale, F.P., Vasquez, L., Kwan, T., Garrido-Martin, D., Watt, S., Yan, Y., Kundu, K., Ecker, S., et al., 2016. Genetic drivers of epigenetic and transcriptional variation in human immune cells. Cell 167, 1398-1414.
    Chen, L.F., Long, H.K., Park, M., Swigut, T., Boettiger, A.N., Wysocka, J., 2023. Structural elements promote architectural stripe formation and facilitate ultra-long-range gene regulation at a human disease locus. Mol. Cell 83, 1446-1461.
    Chen, L.L., 2020. The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat. Rev. Mol. Cell Biol. 21, 475-490.
    Chen, Q., Zhang, X., Shi, J., Yan, M., Zhou, T., 2021. Origins and evolving functionalities of tRNA-derived small RNAs. Trends Biochem. Sci. 46, 790-804.
    Claussnitzer, M., Dankel, S.N., Kim, K.H., Quon, G., Meuleman, W., Haugen, C., Glunk, V., Sousa, I.S., Beaudry, J.L., Puviindran, V., et al., 2015. FTO obesity variant circuitry and adipocyte browning in humans. N. Engl. J. Med. 373, 895-907.
    Clevers, H., 2016. Modeling development and disease with organoids. Cell 165, 1586-1597.
    Cokus, S.J., Feng, S., Zhang, X., Chen, Z., Merriman, B., Haudenschild, C.D., Pradhan, S., Nelson, S.F., Pellegrini, M., Jacobsen, S.E., 2008. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452, 215-219.
    Consortium, E.P., 2004. The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306, 636-640.
    Consortium, E.P., 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74.
    Consortium, G.T., 2013. The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 45, 580-585.
    Creus-Muncunill, J., Guisado-Corcoll, A., Venturi, V., Pantano, L., Escaramis, G., Garcia de Herreros, M., Solaguren-Beascoa, M., Gamez-Valero, A., Navarrete, C., Masana, M., et al., 2021. Huntington's disease brain-derived small RNAs recapitulate associated neuropathology in mice. Acta Neuropathol. 141, 565-584.
    Croce, C.M., 2009. Causes and consequences of microRNA dysregulation in cancer. Nat. Rev. Genet. 10, 704-714.
    Daniel, V.C., Marchionni, L., Hierman, J.S., Rhodes, J.T., Devereux, W.L., Rudin, C.M., Yung, R., Parmigiani, G., Dorsch, M., Peacock, C.D., et al., 2009. A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res. 69, 3364-3373.
    de Almeida, R.C., Chagas, V.S., Castro, M.A.A., Petzl-Erler, M.L., 2018. Integrative analysis identifies genetic variants associated with autoimmune diseases affecting putative microRNA binding sites. Front. Genet. 9, 139.
    de Boni, L., Gasparoni, G., Haubenreich, C., Tierling, S., Schmitt, I., Peitz, M., Koch, P., Walter, J., Wullner, U., Brustle, O., 2018. DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling. Clin. Epigenetics 10, 13.
    De Gobbi, M., Viprakasit, V., Hughes, J.R., Fisher, C., Buckle, V.J., Ayyub, H., Gibbons, R.J., Vernimmen, D., Yoshinaga, Y., de Jong, P., et al., 2006. A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science 312, 1215-1217.
    de Goede, O.M., Nachun, D.C., Ferraro, N.M., Gloudemans, M.J., Rao, A.S., Smail, C., Eulalio, T.Y., Aguet, F., Ng, B., Xu, J., et al., 2021. Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease. Cell 184, 2633-2648.
    de Koning, A.P., Gu, W., Castoe, T.A., Batzer, M.A., Pollock, D.D., 2011. Repetitive elements may comprise over two-thirds of the human genome. PLoS Genet. 7, e1002384.
    Degner, J.F., Pai, A.A., Pique-Regi, R., Veyrieras, J.B., Gaffney, D.J., Pickrell, J.K., De Leon, S., Michelini, K., Lewellen, N., Crawford, G.E., et al., 2012. DNase I sensitivity QTLs are a major determinant of human expression variation. Nature 482, 390-394.
    Desmet, F.O., Hamroun, D., Lalande, M., Collod-Beroud, G., Claustres, M., Beroud, C., 2009. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res. 37, e67.
    Dewachter, L., Brooks, A.N., Noon, K., Cialek, C., Clark-ElSayed, A., Schalck, T., Krishnamurthy, N., Versees, W., Vranken, W., Michiels, J., 2023. Deep mutational scanning of essential bacterial proteins can guide antibiotic development. Nat. Commun. 14, 241.
    Dina, C., Meyre, D., Gallina, S., Durand, E., Korner, A., Jacobson, P., Carlsson, L.M., Kiess, W., Vatin, V., Lecoeur, C., et al., 2007. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat. Genet. 39, 724-726.
    Dixon, J.R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J.S., Ren, B., 2012. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380.
    Dong, K., Shen, J., He, X., Hu, G., Wang, L., Osman, I., Bunting, K.M., Dixon-Melvin, R., Zheng, Z., Xin, H., et al., 2021. CARMN is an evolutionarily conserved smooth muscle cell-specific lncRNA that maintains contractile phenotype by binding myocardin. Circulation 144, 1856-1875.
    Doudna, J.A., Charpentier, E., 2014. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346, 1258096.
    Ellingford, J.M., Ahn, J.W., Bagnall, R.D., Baralle, D., Barton, S., Campbell, C., Downes, K., Ellard, S., Duff-Farrier, C., FitzPatrick, D.R., et al., 2022. Recommendations for clinical interpretation of variants found in non-coding regions of the genome. Genome Med. 14, 73.
    Erdmann, H., Schoberl, F., Giurgiu, M., Leal Silva, R.M., Scholz, V., Scharf, F., Wendlandt, M., Kleinle, S., Deschauer, M., Nubling, G., et al., 2023. Parallel in-depth analysis of repeat expansions in ataxia patients by long-read sequencing. Brain 146, 1831-1843.
    Erkelenz, S., Theiss, S., Otte, M., Widera, M., Peter, J.O., Schaal, H., 2014. Genomic HEXploring allows landscaping of novel potential splicing regulatory elements. Nucleic Acids Res. 42, 10681-10697.
    Espinoza, S., Scarpato, M., Damiani, D., Manago, F., Mereu, M., Contestabile, A., Peruzzo, O., Carninci, P., Santoro, C., Papaleo, F., et al., 2020. SINEUP non-coding RNA targeting GDNF rescues motor deficits and neurodegeneration in a mouse model of Parkinson's disease. Mol. Ther. 28, 642-652.
    Eustermann, S., Schall, K., Kostrewa, D., Lakomek, K., Strauss, M., Moldt, M., Hopfner, K.P., 2018. Structural basis for ATP-dependent chromatin remodelling by the INO80 complex. Nature 556, 386-390.
    Evans, C.M., Fingerlin, T.E., Schwarz, M.I., Lynch, D., Kurche, J., Warg, L., Yang, I.V., Schwartz, D.A., 2016. Idiopathic pulmonary fibrosis: a genetic disease that involves mucociliary dysfunction of the peripheral airways. Physiol. Rev. 96, 1567-1591.
    Fan, X., Yang, Y., Chen, C., Wang, Z., 2022. Pervasive translation of circular RNAs driven by short IRES-like elements. Nat. Commun. 13, 3751.
    Flynt, A.S., Lai, E.C., 2008. Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat. Rev. Genet. 9, 831-842.
    Forrest, M.P., Zhang, H., Moy, W., McGowan, H., Leites, C., Dionisio, L.E., Xu, Z., Shi, J., Sanders, A.R., Greenleaf, W.J., et al., 2017. Open chromatin profiling in hiPSC-derived neurons prioritizes functional noncoding psychiatric risk variants and highlights neurodevelopmental loci. Cell Stem Cell 21, 305-318.
    Franke, M., Ibrahim, D.M., Andrey, G., Schwarzer, W., Heinrich, V., Schopflin, R., Kraft, K., Kempfer, R., Jerkovic, I., Chan, W.L., et al., 2016. Formation of new chromatin domains determines pathogenicity of genomic duplications. Nature 538, 265-269.
    Frankish, A., Carbonell-Sala, S., Diekhans, M., Jungreis, I., Loveland, J.E., Mudge, J.M., Sisu, C., Wright, J.C., Arnan, C., Barnes, I., et al., 2023. GENCODE: reference annotation for the human and mouse genomes in 2023. Nucleic Acids Res. 51, D942-D949.
    Frayling, T.M., Timpson, N.J., Weedon, M.N., Zeggini, E., Freathy, R.M., Lindgren, C.M., Perry, J.R., Elliott, K.S., Lango, H., Rayner, N.W., et al., 2007. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894.
    Frye, M., Harada, B.T., Behm, M., He, C., 2018. RNA modifications modulate gene expression during development. Science 361, 1346-1349.
    Fullwood, M.J., Liu, M.H., Pan, Y.F., Liu, J., Xu, H., Mohamed, Y.B., Orlov, Y.L., Velkov, S., Ho, A., Mei, P.H., et al., 2009. An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 462, 58-64.
    Furlong, E.E.M., Levine, M., 2018. Developmental enhancers and chromosome topology. Science 361, 1341-1345.
    Gacita, A.M., Fullenkamp, D.E., Ohiri, J., Pottinger, T., Puckelwartz, M.J., Nobrega, M.A., McNally, E.M., 2021. Genetic variation in enhancers modifies cardiomyopathy gene expression and progression. Circulation 143, 1302-1316.
    Gallagher, P.G., Steiner, L.A., Liem, R.I., Owen, A.N., Cline, A.P., Seidel, N.E., Garrett, L.J., Bodine, D.M., 2010. Mutation of a barrier insulator in the human ankyrin-1 gene is associated with hereditary spherocytosis. J. Clin. Invest. 120, 4453-4465.
    Gamazon, E.R., Segre, A.V., van de Bunt, M., Wen, X., Xi, H.S., Hormozdiari, F., Ongen, H., Konkashbaev, A., Derks, E.M., Aguet, F., et al., 2018. Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation. Nat. Genet. 50, 956-967.
    Gamazon, E.R., Wheeler, H.E., Shah, K.P., Mozaffari, S.V., Aquino-Michaels, K., Carroll, R.J., Eyler, A.E., Denny, J.C., Consortium, G.T., Nicolae, D.L., et al., 2015. A gene-based association method for mapping traits using reference transcriptome data. Nat. Genet. 47, 1091-1098.
    Gao, Y., Yang, X., Chen, H., Tan, X., Yang, Z., Deng, L., Wang, B., Kong, S., Li, S., Cui, Y., et al., 2023. A pangenome reference of 36 Chinese populations. Nature 619, 112-121.
    Garland, J., Stephen, J., Class, B., Gruber, A., Ciccone, C., Poliak, A., Hayes, C.P., Singhal, V., Slota, C., Perreault, J., et al., 2017. Identification of an Alu element-mediated deletion in the promoter region of GNE in siblings with GNE myopathy. Mol. Genet. Genomic Med. 5, 410-417.
    Gasperini, M., Hill, A.J., McFaline-Figueroa, J.L., Martin, B., Kim, S., Zhang, M.D., Jackson, D., Leith, A., Schreiber, J., Noble, W.S., et al., 2019. A genome-wide framework for mapping gene regulation via cellular genetic screens. Cell 176, 1516.
    Gaudelli, N.M., Komor, A.C., Rees, H.A., Packer, M.S., Badran, A.H., Bryson, D.I., Liu, D.R., 2017. Programmable base editing of A∗T to G∗C in genomic DNA without DNA cleavage. Nature 551, 464-471.
    Gaulton, K.J., Preissl, S., Ren, B., 2023. Interpreting non-coding disease-associated human variants using single-cell epigenomics. Nat. Rev. Genet. 24, 516-534.
    Genomes Project, C., Abecasis, G.R., Auton, A., Brooks, L.D., DePristo, M.A., Durbin, R.M., Handsaker, R.E., Kang, H.M., Marth, G.T., McVean, G.A., 2012. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56-65.
    Ghilardi, N., Wiestner, A., Skoda, R.C., 1998. Thrombopoietin production is inhibited by a translational mechanism. Blood 92, 4023-4030.
    Giacopuzzi, E., Popitsch, N., Taylor, J.C., 2022. GREEN-DB: a framework for the annotation and prioritization of non-coding regulatory variants from whole-genome sequencing data. Nucleic Acids Res. 50, 2522-2535.
    Giambartolomei, C., Vukcevic, D., Schadt, E.E., Franke, L., Hingorani, A.D., Wallace, C., Plagnol, V., 2014. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet. 10, e1004383.
    Giambartolomei, C., Zhenli Liu, J., Zhang, W., Hauberg, M., Shi, H., Boocock, J., Pickrell, J., Jaffe, A.E., CommonMind, C., Pasaniuc, B., et al., 2018. A Bayesian framework for multiple trait colocalization from summary association statistics. Bioinformatics 34, 2538-2545.
    Giri, A.K., Aavikko, M., Wartiovaara, L., Lemmetyinen, T., Karjalainen, J., Mehtonen, J., Palin, K., Valimaki, N., Tamlander, M., Saikkonen, R., et al., 2023. Genome wide association study identifies 4 novel risk loci for small intestinal neuroendocrine tumors including a missense mutation in LGR5. Gastroenterology 165, 861-873.
    Greenbaum, J., Deng, H.W., 2017. A statistical approach to fine mapping for the identification of potential causal variants related to bone mineral density. J. Bone Miner. Res. 32, 1651-1658.
    Greenberg, M.V.C., Bourc'his, D., 2019. The diverse roles of DNA methylation in mammalian development and disease. Nat. Rev. Mol. Cell Biol. 20, 590-607.
    Grigelioniene, G., Suzuki, H.I., Taylan, F., Mirzamohammadi, F., Borochowitz, Z.U., Ayturk, U.M., Tzur, S., Horemuzova, E., Lindstrand, A., Weis, M.A., et al., 2019. Gain-of-function mutation of microRNA-140 in human skeletal dysplasia. Nat. Med. 25, 583-590.
    Griger, J., Widholz, S.A., Jesinghaus, M., de Andrade Kratzig, N., Lange, S., Engleitner, T., Montero, J.J., Zhigalova, E., Ollinger, R., Suresh, V., et al., 2023. An integrated cellular and molecular model of gastric neuroendocrine cancer evolution highlights therapeutic targets. Cancer Cell 41, 1327-1344.
    Grosselin, K., Durand, A., Marsolier, J., Poitou, A., Marangoni, E., Nemati, F., Dahmani, A., Lameiras, S., Reyal, F., Frenoy, O., et al., 2019. High-throughput single-cell ChIP-seq identifies heterogeneity of chromatin states in breast cancer. Nat. Genet. 51, 1060-1066.
    Gudmundsson, J., Sulem, P., Rafnar, T., Bergthorsson, J.T., Manolescu, A., Gudbjartsson, D., Agnarsson, B.A., Sigurdsson, A., Benediktsdottir, K.R., Blondal, T., et al., 2008. Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. Nat. Genet. 40, 281-283.
    Guo, J., Wu, Y., Zhu, Z., Zheng, Z., Trzaskowski, M., Zeng, J., Robinson, M.R., Visscher, P.M., Yang, J., 2018. Global genetic differentiation of complex traits shaped by natural selection in humans. Nat. Commun. 9, 1865.
    Guo, L., Wang, J., 2018. rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks. Nucleic Acids Res. 46, D1111-D1116.
    Gupta, R.M., Hadaya, J., Trehan, A., Zekavat, S.M., Roselli, C., Klarin, D., Emdin, C.A., Hilvering, C.R.E., Bianchi, V., Mueller, C., et al., 2017. A genetic variant associated with five vascular diseases is a distal regulator of endothelin-1 gene expression. Cell 170, 522-533.
    Gusev, A., Ko, A., Shi, H., Bhatia, G., Chung, W., Penninx, B.W., Jansen, R., de Geus, E.J., Boomsma, D.I., Wright, F.A., et al., 2016. Integrative approaches for large-scale transcriptome-wide association studies. Nat. Genet. 48, 245-252.
    Guzzi, N., Ciesla, M., Ngoc, P.C.T., Lang, S., Arora, S., Dimitriou, M., Pimkova, K., Sommarin, M.N.E., Munita, R., Lubas, M., et al., 2018. Pseudouridylation of tRNA-derived fragments steers translational control in stem cells. Cell 173, 1204-1216.
    Guzzi, N., Muthukumar, S., Ciesla, M., Todisco, G., Ngoc, P.C.T., Madej, M., Munita, R., Fazio, S., Ekstrom, S., Mortera-Blanco, T., et al., 2022. Pseudouridine-modified tRNA fragments repress aberrant protein synthesis and predict leukaemic progression in myelodysplastic syndrome. Nat. Cell Biol. 24, 299-306.
    Haberle, V., Stark, A., 2018. Eukaryotic core promoters and the functional basis of transcription initiation. Nat. Rev. Mol. Cell Biol. 19, 621-637.
    Hannan, A.J., 2010. Tandem repeat polymorphisms: modulators of disease susceptibility and candidates for 'missing heritability'. Trends Genet. 26, 59-65.
    Hannon, E., Spiers, H., Viana, J., Pidsley, R., Burrage, J., Murphy, T.M., Troakes, C., Turecki, G., O'Donovan, M.C., Schalkwyk, L.C., et al., 2016. Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci. Nat. Neurosci. 19, 48-54.
    Hansen, T.B., Jensen, T.I., Clausen, B.H., Bramsen, J.B., Finsen, B., Damgaard, C.K., Kjems, J., 2013. Natural RNA circles function as efficient microRNA sponges. Nature 495, 384-388.
    Heberle, E., Bardet, A.F., 2019. Sensitivity of transcription factors to DNA methylation. Essays Biochem. 63, 727-741.
    Hindorff, L.A., Sethupathy, P., Junkins, H.A., Ramos, E.M., Mehta, J.P., Collins, F.S., Manolio, T.A., 2009. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. U. S. A. 106, 9362-9367.
    Hinnebusch, A.G., Ivanov, I.P., Sonenberg, N., 2016. Translational control by 5'-untranslated regions of eukaryotic mRNAs. Science 352, 1413-1416.
    Hormozdiari, F., Kostem, E., Kang, E.Y., Pasaniuc, B., Eskin, E., 2014. Identifying causal variants at loci with multiple signals of association. Genetics 198, 497-508.
    Hsieh, T.S., Cattoglio, C., Slobodyanyuk, E., Hansen, A.S., Rando, O.J., Tjian, R., Darzacq, X., 2020. Resolving the 3D Landscape of transcription-linked mammalian chromatin folding. Mol. Cell 78, 539-553.
    Huang, D., Zhou, Y., Yi, X., Fan, X., Wang, J., Yao, H., Sham, P.C., Hao, J., Chen, K., Li, M.J., 2022. VannoPortal: multiscale functional annotation of human genetic variants for interrogating molecular mechanism of traits and diseases. Nucleic Acids Res. 50, D1408-D1416.
    Huang, J.Z., Chen, M., Chen, D., Gao, X.C., Zhu, S., Huang, H., Hu, M., Zhu, H., Yan, G.R., 2017. A peptide encoded by a putative lncRNA HOXB-AS3 suppresses colon cancer growth. Mol. Cell 68, 171-184.
    Hughes, A.E., Bradley, D.T., Campbell, M., Lechner, J., Dash, D.P., Simpson, D.A., Willoughby, C.E., 2011. Mutation altering the miR-184 seed region causes familial keratoconus with cataract. Am. J. Hum. Genet. 89, 628-633.
    Idda, M.L., Lodde, V., McClusky, W.G., Martindale, J.L., Yang, X., Munk, R., Steri, M., Orru, V., Mulas, A., Cucca, F., et al., 2018. Cooperative translational control of polymorphic BAFF by NF90 and miR-15a. Nucleic Acids Res. 46, 12040-12051.
    International Human Genome Sequencing, C., 2004. Finishing the euchromatic sequence of the human genome. Nature 431, 931-945.
    Islam, S., Kjallquist, U., Moliner, A., Zajac, P., Fan, J.B., Lonnerberg, P., Linnarsson, S., 2011. Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. Genome Res. 21, 1160-1167.
    Jain, A., Vale, R.D., 2017. RNA phase transitions in repeat expansion disorders. Nature 546, 243-247.
    Jia, R., Chai, P., Zhang, H., Fan, X., 2017. Novel insights into chromosomal conformations in cancer. Mol. Cancer 16, 173.
    Kaplow, I.M., MacIsaac, J.L., Mah, S.M., McEwen, L.M., Kobor, M.S., Fraser, H.B., 2015. A pooling-based approach to mapping genetic variants associated with DNA methylation. Genome Res. 25, 907-917.
    Karczewski, K.J., Snyder, M.P., 2018. Integrative omics for health and disease. Nat. Rev. Genet. 19, 299-310.
    Kim, D., Lim, K., Kim, S.T., Yoon, S.H., Kim, K., Ryu, S.M., Kim, J.S., 2017. Genome-wide target specificities of CRISPR RNA-guided programmable deaminases. Nat. Biotechnol. 35, 475-480.
    Kim, J.W., Yin, X., Jhaldiyal, A., Khan, M.R., Martin, I., Xie, Z., Perez-Rosello, T., Kumar, M., Abalde-Atristain, L., Xu, J., et al., 2020. Defects in mRNA translation in LRRK2-Mutant hiPSC-derived dopaminergic neurons lead to dysregulated calcium homeostasis. Cell Stem Cell 27, 633-645.
    Kim, S., Wysocka, J., 2023. Deciphering the multi-scale, quantitative cis-regulatory code. Mol. Cell 83, 373-392.
    Kino, Y., Mori, D., Oma, Y., Takeshita, Y., Sasagawa, N., Ishiura, S., 2004. Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats. Hum. Mol. Genet. 13, 495-507.
    Kircher, M., Witten, D.M., Jain, P., O'Roak, B.J., Cooper, G.M., Shendure, J., 2014. A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet. 46, 310-315.
    Koehler, K.R., Mikosz, A.M., Molosh, A.I., Patel, D., Hashino, E., 2013. Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature 500, 217-221.
    Kulakovskiy, I.V., Medvedeva, Y.A., Schaefer, U., Kasianov, A.S., Vorontsov, I.E., Bajic, V.B., Makeev, V.J., 2013. HOCOMOCO: a comprehensive collection of human transcription factor binding sites models. Nucleic Acids Res. 41, D195-D202.
    LaCroix, A.J., Stabley, D., Sahraoui, R., Adam, M.P., Mehaffey, M., Kernan, K., Myers, C.T., Fagerstrom, C., Anadiotis, G., Akkari, Y.M., et al., 2019. GGC repeat expansion and exon 1 methylation of XYLT1 is a common pathogenic variant in Baratela-Scott syndrome. Am. J. Hum. Genet. 104, 35-44.
    Lancaster, M.A., Knoblich, J.A., 2014. Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345, 1247125.
    Lederer, D., Grisart, B., Digilio, M.C., Benoit, V., Crespin, M., Ghariani, S.C., Maystadt, I., Dallapiccola, B., Verellen-Dumoulin, C., 2012. Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. Am. J. Hum. Genet. 90, 119-124.
    Lee, D., Gorkin, D.U., Baker, M., Strober, B.J., Asoni, A.L., McCallion, A.S., Beer, M.A., 2015. A method to predict the impact of regulatory variants from DNA sequence. Nat. Genet. 47, 955-961.
    Lei, X., Tian, X., Wang, H., Xu, X., Li, G., Liu, W., Wang, D., Xiao, Z., Zhang, M., Li, M.J., et al., 2023. Noncoding SNP at rs1663689 represses ADGRG6 via interchromosomal interaction and reduces lung cancer progression. EMBO Rep. 24, e56212.
    Lemire, M., Zaidi, S.H., Ban, M., Ge, B., Aissi, D., Germain, M., Kassam, I., Wang, M., Zanke, B.W., Gagnon, F., et al., 2015. Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci. Nat. Commun. 6, 6326.
    Lemmers, R., Butterfield, R., van der Vliet, P.J., de Bleecker, J.L., van der Pol, L., Dunn, D.M., Erasmus, C.E., D'Hooghe, M., Verhoeven, K., Balog, J., et al., 2023. Autosomal dominant in cis D4Z4 repeat array duplication alleles in facioscapulohumeral dystrophy. Brain 2023, awad312.
    Leonard, M.M., Karathia, H., Pujolassos, M., Troisi, J., Valitutti, F., Subramanian, P., Camhi, S., Kenyon, V., Colucci, A., Serena, G., et al., 2020. Multi-omics analysis reveals the influence of genetic and environmental risk factors on developing gut microbiota in infants at risk of celiac disease. Microbiome 8, 130.
    Leppek, K., Das, R., Barna, M., 2018. Functional 5' UTR mRNA structures in eukaryotic translation regulation and how to find them. Nat. Rev. Mol. Cell Biol. 19, 158-174.
    Lewis, M.A., Quint, E., Glazier, A.M., Fuchs, H., De Angelis, M.H., Langford, C., van Dongen, S., Abreu-Goodger, C., Piipari, M., Redshaw, N., et al., 2009. An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat. Genet. 41, 614-618.
    Li, Li Z., Chen, R., Lian, M., Wang, H., Wei, Y., You, Z., Zhang, J., Li, B., Li, Y., et al., 2023a. A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression. Nat. Commun. 14, 1732.
    Li, Xi W., Bai, Y., Liu, X., Zhang, Y., Li, L., Bian, L., Liu, C., Tang, Y., Shen, L., et al., 2023b. FTO-dependent m(6)A modification of Plpp3 in circSCMH1-regulated vascular repair and functional recovery following stroke. Nat. Commun. 14, 489.
    Li, J., Sun, D., Pu, W., Wang, J., Peng, Y., 2020. Circular RNAs in cancer: biogenesis, function, and clinical significance. Trends Cancer 6, 319-336.
    Li, Yan C., 2023c. GLUE multimodal single cell data. Precis Clin. Med. 6, pbad007.
    Li, J., Zhu, L., Cheng, J., Peng, Y., 2021. Transfer RNA-derived small RNA: A rising star in oncology. Semin Cancer Biol. 75, 29-37.
    Liang, D., Elwell, A.L., Aygun, N., Krupa, O., Wolter, J.M., Kyere, F.A., Lafferty, M.J., Cheek, K.E., Courtney, K.P., Yusupova, M., et al., 2021. Cell-type-specific effects of genetic variation on chromatin accessibility during human neuronal differentiation. Nat. Neurosci. 24, 941-953.
    Liao, W.W., Asri, M., Ebler, J., Doerr, D., Haukness, M., Hickey, G., Lu, S., Lucas, J.K., Monlong, J., Abel, H.J., et al., 2023. A draft human pangenome reference. Nature 617, 312-324.
    Libioulle, C., Louis, E., Hansoul, S., Sandor, C., Farnir, F., Franchimont, D., Vermeire, S., Dewit, O., de Vos, M., Dixon, A., et al., 2007. Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet. 3, e58.
    Lieberman-Aiden, E., van Berkum, N.L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B.R., Sabo, P.J., Dorschner, M.O., et al., 2009. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289-293.
    Liu, D., Nguyen, T.T.L., Gao, H., Huang, H., Kim, D.C., Sharp, B., Ye, Z., Lee, J.H., Coombes, B.J., Ordog, T., et al., 2021. TCF7L2 lncRNA: a link between bipolar disorder and body mass index through glucocorticoid signaling. Mol. Psychiatry 26, 7454-7464.
    Liu, S.J., Dang, H.X., Lim, D.A., Feng, F.Y., Maher, C.A., 2021. Long noncoding RNAs in cancer metastasis. Nat. Rev. Cancer 21, 446-460.
    Liu, T., Ortiz, J.A., Taing, L., Meyer, C.A., Lee, B., Zhang, Y., Shin, H., Wong, S.S., Ma, J., Lei, Y., et al., 2011. Cistrome: an integrative platform for transcriptional regulation studies. Genome Biol. 12, R83.
    Liu, Y., Cheng, Z., Pang, Y., Cui, L., Qian, T., Quan, L., Zhao, H., Shi, J., Ke, X., Fu, L., 2019. Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia. J. Hematol. Oncol. 12, 51.
    Liu, Z., Lu, Z., Yang, G., Huang, S., Li, G., Feng, S., Liu, Y., Li, J., Yu, W., Zhang, Y., et al., 2018. Efficient generation of mouse models of human diseases via ABE- and BE-mediated base editing. Nat. Commun. 9, 2338.
    Lu, S., Wang, T., Zhang, G., He, Q.Y., 2020. Understanding the proteome encoded by "non-coding RNAs": new insights into human genome. Sci. China Life Sci. 63, 986-995.
    Lu, Y., Quan, C., Chen, H., Bo, X., Zhang, C., 2017. 3DSNP: a database for linking human noncoding SNPs to their three-dimensional interacting genes. Nucleic Acids Res. 45, D643-D649.
    Lupianez, D.G., Kraft, K., Heinrich, V., Krawitz, P., Brancati, F., Klopocki, E., Horn, D., Kayserili, H., Opitz, J.M., Laxova, R., et al., 2015. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161, 1012-1025.
    Lutz, M.W., Chiba-Falek, O., 2023. Bioinformatics pipeline to guide post-GWAS studies in Alzheimer's: A new catalogue of disease candidate short structural variants. Alzheimers Dement. 19, 4094-4109.
    MacArthur, J., Bowler, E., Cerezo, M., Gil, L., Hall, P., Hastings, E., Junkins, H., McMahon, A., Milano, A., Morales, J., et al., 2017. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 45, D896-D901.
    Man, J.C.K., Bosada, F.M., Scholman, K.T., Offerhaus, J.A., Walsh, R., van Duijvenboden, K., van Eif, V.W.W., Bezzina, C.R., Verkerk, A.O., Boukens, B.J., et al., 2021. Variant intronic enhancer controls SCN10A-short expression and heart conduction. Circulation 144, 229-242.
    Manghwar, H., Li, B., Ding, X., Hussain, A., Lindsey, K., Zhang, X., Jin, S., 2020. CRISPR/Cas Systems in genome editing: methodologies and tools for sgRNA design, off-target evaluation, and strategies to mitigate off-target effects. Adv. Sci. 7, 1902312.
    Manickam, C., Shah, S.V., Lucar, O., Ram, D.R., Reeves, R.K., 2018. Cytokine-mediated tissue injury in non-human primate models of viral infections. Front. Immunol. 9, 2862.
    Mao, F., Liu, Q., Zhao, X., Yang, H., Guo, S., Xiao, L., Li, X., Teng, H., Sun, Z., Dou, Y., 2018. EpiDenovo: a platform for linking regulatory de novo mutations to developmental epigenetics and diseases. Nucleic Acids Res. 46, D92-D99.
    Martire, S., Banaszynski, L.A., 2020. The roles of histone variants in fine-tuning chromatin organization and function. Nat. Rev. Mol. Cell Biol. 21, 522-541.
    Mattick, J.S., Rinn, J.L., 2015. Discovery and annotation of long noncoding RNAs. Nat. Struct. Mol. Biol. 22, 5-7.
    Maurano, M.T., Humbert, R., Rynes, E., Thurman, R.E., Haugen, E., Wang, H., Reynolds, A.P., Sandstrom, R., Qu, H., Brody, J., et al., 2012. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190-1195.
    Maynard, K.R., Collado-Torres, L., Weber, L.M., Uytingco, C., Barry, B.K., Williams, S.R., Catallini, J.L., 2nd, Tran, M.N., Besich, Z., Tippani, M., et al., 2021. Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex. Nat. Neurosci. 24, 425-436.
    Mayr, C., 2016. Evolution and Biological Roles of Alternative 3'UTRs. Trends Cell Biol. 26, 227-237.
    McGovern, A., Schoenfelder, S., Martin, P., Massey, J., Duffus, K., Plant, D., Yarwood, A., Pratt, A.G., Anderson, A.E., Isaacs, J.D., et al., 2016. Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23. Genome Biol. 17, 212.
    McPherson, R., Pertsemlidis, A., Kavaslar, N., Stewart, A., Roberts, R., Cox, D.R., Hinds, D.A., Pennacchio, L.A., Tybjaerg-Hansen, A., Folsom, A.R., et al., 2007. A common allele on chromosome 9 associated with coronary heart disease. Science 316, 1488-1491.
    McVicker, G., van de Geijn, B., Degner, J.F., Cain, C.E., Banovich, N.E., Raj, A., Lewellen, N., Myrthil, M., Gilad, Y., Pritchard, J.K., 2013. Identification of genetic variants that affect histone modifications in human cells. Science 342, 747-749.
    Megiorni, F., Cialfi, S., Dominici, C., Quattrucci, S., Pizzuti, A., 2011. Synergistic post-transcriptional regulation of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) by miR-101 and miR-494 specific binding. PLoS One 6, e26601.
    Mellor, J., 2006. It takes a PHD to read the histone code. Cell 126, 22-24.
    Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S.D., Gregersen, L.H., Munschauer, M., et al., 2013. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495, 333-338.
    Mencia, A., Modamio-Hoybjor, S., Redshaw, N., Morin, M., Mayo-Merino, F., Olavarrieta, L., Aguirre, L.A., del Castillo, I., Steel, K.P., Dalmay, T., et al., 2009. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat. Genet. 41, 609-613.
    Meseguer, S., Navarro-Gonzalez, C., Panadero, J., Villarroya, M., Boutoual, R., Sanchez-Alcazar, J.A., Armengod, M.E., 2019. The MELAS mutation m.3243A>G alters the expression of mitochondrial tRNA fragments. Biochim. Biophys. Acta Mol. Cell Res. 1866, 1433-1449.
    Miguel-Escalada, I., Maestro, M.A., Balboa, D., Elek, A., Bernal, A., Bernardo, E., Grau, V., Garcia-Hurtado, J., Sebe-Pedros, A., Ferrer, J., 2022. Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster. Dev. Cell 57, 1922-1936.
    Mika, K.M., Lynch, V.J., 2016. An Ancient Fecundability-Associated Polymorphism Switches a Repressor into an Enhancer of Endometrial TAP2 Expression. Am. J. Hum. Genet. 99, 1059-1071.
    Miotto, R., Wang, F., Wang, S., Jiang, X., Dudley, J.T., 2018. Deep learning for healthcare: review, opportunities and challenges. Brief Bioinform. 19, 1236-1246.
    Mitchell, S.J., Scheibye-Knudsen, M., Longo, D.L., de Cabo, R., 2015. Animal models of aging research: implications for human aging and age-related diseases. Annu. Rev. Anim. Biosci. 3, 283-303.
    Moore, S.T., Nakamura, T., Nie, J., Solivais, A.J., Aristizabal-Ramirez, I., Ueda, Y., Manikandan, M., Reddy, V.S., Romano, D.R., Hoffman, J.R., et al., 2023. Generating high-fidelity cochlear organoids from human pluripotent stem cells. Cell Stem Cell 30, 950-961.
    Morova, T., Ding, Y., Huang, C.F., Sar, F., Schwarz, T., Giambartolomei, C., Baca, S.C., Grishin, D., Hach, F., Gusev, A., et al., 2023. Optimized high-throughput screening of non-coding variants identified from genome-wide association studies. Nucleic Acids Res. 51, e18.
    Mucaki, E.J., Shirley, B.C., Rogan, P.K., 2013. Prediction of mutant mRNA splice isoforms by information theory-based exon definition. Hum. Mutat. 34, 557-565.
    Mulqueen, R.M., Pokholok, D., Norberg, S.J., Torkenczy, K.A., Fields, A.J., Sun, D., Sinnamon, J.R., Shendure, J., Trapnell, C., O'Roak, B.J., et al., 2018. Highly scalable generation of DNA methylation profiles in single cells. Nat. Biotechnol. 36, 428-431.
    Mumbach, M.R., Satpathy, A.T., Boyle, E.A., Dai, C., Gowen, B.G., Cho, S.W., Nguyen, M.L., Rubin, A.J., Granja, J.M., Kazane, K.R., et al., 2017. Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements. Nat. Genet. 49, 1602-1612.
    Nabavizadeh, N., Bressin, A., Shboul, M., Moreno Traspas, R., Chia, P.H., Bonnard, C., Szenker-Ravi, E., Saribas, B., Beillard, E., Altunoglu, U., et al., 2023. A progeroid syndrome caused by a deep intronic variant in TAPT1 is revealed by RNA/SI-NET sequencing. EMBO Mol. Med. 15, e16478.
    Narendra, V., Rocha, P.P., An, D., Raviram, R., Skok, J.A., Mazzoni, E.O., Reinberg, D., 2015. CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. Science 347, 1017-1021.
    Nelson, B.R., Makarewich, C.A., Anderson, D.M., Winders, B.R., Troupes, C.D., Wu, F., Reese, A.L., McAnally, J.R., Chen, X., Kavalali, E.T., et al., 2016. A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science 351, 271-275.
    Nelson, P., Kiriakidou, M., Sharma, A., Maniataki, E., Mourelatos, Z., 2003. The microRNA world: small is mighty. Trends Biochem. Sci. 28, 534-540.
    Ng, S.B., Bigham, A.W., Buckingham, K.J., Hannibal, M.C., McMillin, M.J., Gildersleeve, H.I., Beck, A.E., Tabor, H.K., Cooper, G.M., Mefford, H.C., et al., 2010. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat. Genet. 42, 790-793.
    Nora, E.P., Lajoie, B.R., Schulz, E.G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N.L., Meisig, J., Sedat, J., et al., 2012. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485, 381-385.
    Nurk, S., Koren, S., Rhie, A., Rautiainen, M., Bzikadze, A.V., Mikheenko, A., Vollger, M.R., Altemose, N., Uralsky, L., Gershman, A., et al., 2022. The complete sequence of a human genome. Science 376, 44-53.
    Oner, R., Agarwal, S., Dimovski, A.J., Efremov, G.D., Petkov, G.H., Altay, C., Gurgey, A., Huisman, T.H., 1991. The G----A mutation at position +22 3' to the Cap site of the beta-globin gene as a possible cause for a beta-thalassemia. Hemoglobin 15, 67-76.
    Pan, Q., Liu, Y.J., Bai, X.F., Han, X.L., Jiang, Y., Ai, B., Shi, S.S., Wang, F., Xu, M.C., Wang, Y.Z., et al., 2021. VARAdb: a comprehensive variation annotation database for human. Nucleic Acids Res. 49, D1431-D1444.
    Pang, B., Snyder, M.P., 2020. Systematic identification of silencers in human cells. Nat. Genet. 52, 254-263.
    Park, O.H., Ha, H., Lee, Y., Boo, S.H., Kwon, D.H., Song, H.K., Kim, Y.K., 2019. Endoribonucleolytic Cleavage of m(6)A-Containing RNAs by RNase P/MRP Complex. Mol. Cell 74, 494-507.
    Pasquinelli, A.E., 2012. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat. Rev. Genet. 13, 271-282.
    Perlman, R.L., 2016. Mouse models of human disease: an evolutionary perspective. Evol. Med. Public Health 2016, 170-176.
    Pertea, M., Lin, X., Salzberg, S.L., 2001. GeneSplicer: a new computational method for splice site prediction. Nucleic Acids Res. 29, 1185-1190.
    Pickar-Oliver, A., Gersbach, C.A., 2019. The next generation of CRISPR-Cas technologies and applications. Nat. Rev. Mol. Cell Biol. 20, 490-507.
    Plaisancie, J., Tarilonte, M., Ramos, P., Jeanton-Scaramouche, C., Gaston, V., Dollfus, H., Aguilera, D., Kaplan, J., Fares-Taie, L., Blanco-Kelly, F., et al., 2018. Implication of non-coding PAX6 mutations in aniridia. Hum. Genet. 137, 831-846.
    Porcu, E., Rueger, S., Lepik, K., e, Q.C., Consortium, B., Santoni, F.A., Reymond, A., Kutalik, Z., 2019. Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits. Nat. Commun. 10, 3300.
    Quan, C., Ping, J., Lu, H., Zhou, G., Lu, Y., 2022. 3DSNP 2.0: update and expansion of the noncoding genomic variant annotation database. Nucleic Acids Res. 50, D950-D955.
    Quang, D., Chen, Y., Xie, X., 2015. DANN: a deep learning approach for annotating the pathogenicity of genetic variants. Bioinformatics 31, 761-763.
    Racko, D., Benedetti, F., Dorier, J., Stasiak, A., 2019. Are TADs supercoiled? Nucleic Acids Res. 47, 521-532.
    Ramani, V., Deng, X., Qiu, R., Gunderson, K.L., Steemers, F.J., Disteche, C.M., Noble, W.S., Duan, Z., Shendure, J., 2017. Massively multiplex single-cell Hi-C. Nat. Methods 14, 263-266.
    Raponi, M., Buratti, E., Dassie, E., Upadhyaya, M., Baralle, D., 2009. Low U1 snRNP dependence at the NF1 exon 29 donor splice site. FEBS J. 276, 2060-2073.
    Raponi, M., Upadhyaya, M., Baralle, D., 2006. Functional splicing assay shows a pathogenic intronic mutation in neurofibromatosis type 1 (NF1) due to intronic sequence exonization. Hum. Mutat. 27, 294-295.
    Ritchie, G.R., Dunham, I., Zeggini, E., Flicek, P., 2014. Functional annotation of noncoding sequence variants. Nat. Methods 11, 294-296.
    Robertson, G., Hirst, M., Bainbridge, M., Bilenky, M., Zhao, Y., Zeng, T., Euskirchen, G., Bernier, B., Varhol, R., Delaney, A., et al., 2007. Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing. Nat. Methods 4, 651-657.
    Robertson, K.D., 2005. DNA methylation and human disease. Nat. Rev. Genet. 6, 597-610.
    Rosenbloom, K.R., Armstrong, J., Barber, G.P., Casper, J., Clawson, H., Diekhans, M., Dreszer, T.R., Fujita, P.A., Guruvadoo, L., Haeussler, M., et al., 2015. The UCSC genome browser database: 2015 update. Nucleic Acids Res. 43, D670-D681.
    Roundtree, I.A., Evans, M.E., Pan, T., He, C., 2017. Dynamic RNA modifications in gene expression regulation. Cell 169, 1187-1200.
    Sandelin, A., Alkema, W., Engstrom, P., Wasserman, W.W., Lenhard, B., 2004. JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Res. 32, D91-D94.
    Schmidt, D., Wilson, M.D., Ballester, B., Schwalie, P.C., Brown, G.D., Marshall, A., Kutter, C., Watt, S., Martinez-Jimenez, C.P., Mackay, S., et al., 2010. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science 328, 1036-1040.
    Scotti, M.M., Swanson, M.S., 2016. RNA mis-splicing in disease. Nat. Rev. Genet. 17, 19-32.
    Segert, J.A., Gisselbrecht, S.S., Bulyk, M.L., 2021. Transcriptional silencers: driving gene expression with the brakes on. Trends Genet. 37, 514-527.
    Seok, J., Warren, H.S., Cuenca, A.G., Mindrinos, M.N., Baker, H.V., Xu, W., Richards, D.R., McDonald-Smith, G.P., Gao, H., Hennessy, L., et al., 2013. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc. Natl. Acad. Sci. U. S. A. 110, 3507-3512.
    Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., Cavalli, G., 2012. Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148, 458-472.
    Sgourou, A., Routledge, S., Antoniou, M., Papachatzopoulou, A., Psiouri, L., Athanassiadou, A., 2004. Thalassaemia mutations within the 5'UTR of the human beta-globin gene disrupt transcription. Br J. Haematol. 124, 828-835.
    Shah, S., Sharp, K.J., Raju Ponny, S., Lee, J., Watts, J.K., Berry-Kravis, E., Richter, J.D., 2023. Antisense oligonucleotide rescue of CGG expansion-dependent FMR1 mis-splicing in fragile X syndrome restores FMRP. Proc. Natl. Acad. Sci. U. S. A. 120, e2302534120.
    Shaheen, R., Tasak, M., Maddirevula, S., Abdel-Salam, G.M.H., Sayed, I.S.M., Alazami, A.M., Al-Sheddi, T., Alobeid, E., Phizicky, E.M., Alkuraya, F.S., 2019. PUS7 mutations impair pseudouridylation in humans and cause intellectual disability and microcephaly. Hum. Genet. 138, 231-239.
    Shihab, H.A., Gough, J., Cooper, D.N., Stenson, P.D., Barker, G.L., Edwards, K.J., Day, I.N., Gaunt, T.R., 2013. Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Hum. Mutat. 34, 57-65.
    Shihab, H.A., Rogers, M.F., Gough, J., Mort, M., Cooper, D.N., Day, I.N., Gaunt, T.R., Campbell, C., 2015. An integrative approach to predicting the functional effects of non-coding and coding sequence variation. Bioinformatics 31, 1536-1543.
    Sims, R.J., 3rd, Reinberg, D., 2008. Is there a code embedded in proteins that is based on post-translational modifications? Nat. Rev. Mol. Cell Biol. 9, 815-820.
    Smallwood, S.A., Lee, H.J., Angermueller, C., Krueger, F., Saadeh, H., Peat, J., Andrews, S.R., Stegle, O., Reik, W., Kelsey, G., 2014. Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat. Methods 11, 817-820.
    Smith, A.K., Kilaru, V., Kocak, M., Almli, L.M., Mercer, K.B., Ressler, K.J., Tylavsky, F.A., Conneely, K.N., 2014. Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. BMC Genomics 15, 145.
    Sobala, A., Hutvagner, G., 2013. Small RNAs derived from the 5' end of tRNA can inhibit protein translation in human cells. RNA Biol 10, 553-563.
    Stacey, S.N., Manolescu, A., Sulem, P., Rafnar, T., Gudmundsson, J., Gudjonsson, S.A., Masson, G., Jakobsdottir, M., Thorlacius, S., Helgason, A., et al., 2007. Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat. Genet. 39, 865-869.
    Stahl, P.L., Salmen, F., Vickovic, S., Lundmark, A., Navarro, J.F., Magnusson, J., Giacomello, S., Asp, M., Westholm, J.O., Huss, M., et al., 2016. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 353, 78-82.
    Steri, M., Idda, M.L., Whalen, M.B., Orru, V., 2018. Genetic variants in mRNA untranslated regions. Wiley Interdiscip. Rev. RNA 9, e1474.
    Stewart, T.P., Kim, H.Y., Saxton, A.M., Kim, J.H., 2010. Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J x TALLYHO/JngJ) F2 mice. BMC Genomics 11, 713.
    Stunnenberg, H.G., International Human Epigenome, C., Hirst, M., 2016. The international human epigenome consortium: a blueprint for scientific collaboration and discovery. Cell 167, 1145-1149.
    Sun, Y.M., Chen, Y.Q., 2020. Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application. J. Hematol. Oncol. 13, 109.
    Suter, C.M., Martin, D.I., Ward, R.L., 2004. Germline epimutation of MLH1 in individuals with multiple cancers. Nat. Genet. 36, 497-501.
    Suzuki, M.M., Bird, A., 2008. DNA methylation landscapes: provocative insights from epigenomics. Nat. Rev. Genet. 9, 465-476.
    Tagliafierro, L., Glenn, O.C., Zamora, M.E., Beach, T.G., Woltjer, R.L., Lutz, M.W., Chiba-Falek, O., 2017. Genetic analysis of alpha-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies. Alzheimers Dement 13, 1237-1250.
    Tehranchi, A.K., Myrthil, M., Martin, T., Hie, B.L., Golan, D., Fraser, H.B., 2016. Pooled ChIP-Seq Links Variation in Transcription Factor Binding to Complex Disease Risk. Cell 165, 730-741.
    Tenney, A.P., Di Gioia, S.A., Webb, B.D., Chan, W.M., de Boer, E., Garnai, S.J., Barry, B.J., Ray, T., Kosicki, M., Robson, C.D., et al., 2023. Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis. Nat. Genet. 55, 1149-1163.
    Tessarz, P., Kouzarides, T., 2014. Histone core modifications regulating nucleosome structure and dynamics. Nat. Rev. Mol. Cell Biol. 15, 703-708.
    Theodoris, C.V., Xiao, L., Chopra, A., Chaffin, M.D., Al Sayed, Z.R., Hill, M.C., Mantineo, H., Brydon, E.M., Zeng, Z., Liu, X.S., et al., 2023. Transfer learning enables predictions in network biology. Nature 618, 616-624.
    Thomas, E.D., Timms, A.E., Giles, S., Harkins-Perry, S., Lyu, P., Hoang, T., Qian, J., Jackson, V.E., Bahlo, M., Blackshaw, S., et al., 2022. Cell-specific cis-regulatory elements and mechanisms of non-coding genetic disease in human retina and retinal organoids. Dev. Cell 57, 820-836.
    Todd, J.A., Walker, N.M., Cooper, J.D., Smyth, D.J., Downes, K., Plagnol, V., Bailey, R., Nejentsev, S., Field, S.F., Payne, F., et al., 2007. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat. Genet. 39, 857-864.
    Tran, K.A., Kondrashova, O., Bradley, A., Williams, E.D., Pearson, J.V., Waddell, N., 2021. Deep learning in cancer diagnosis, prognosis and treatment selection. Genome Med. 13, 152.
    Trangle, S.S., Rosenberg, T., Parnas, H., Levy, G., Bar, E., Marco, A., Barak, B., 2023. In individuals with Williams syndrome, dysregulation of methylation in non-coding regions of neuronal and oligodendrocyte DNA is associated with pathology and cortical development. Mol. Psychiatry 28, 1112-1127.
    Udd, B., Krahe, R., 2012. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol. 11, 891-905.
    van Haaften, G., Dalgliesh, G.L., Davies, H., Chen, L., Bignell, G., Greenman, C., Edkins, S., Hardy, C., O'Meara, S., Teague, J., et al., 2009. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat. Genet. 41, 521-523.
    Vandereyken, K., Sifrim, A., Thienpont, B., Voet, T., 2023. Methods and applications for single-cell and spatial multi-omics. Nat. Rev. Genet. 24, 494-515.
    Verkerk, A.J., Pieretti, M., Sutcliffe, J.S., Fu, Y.H., Kuhl, D.P., Pizzuti, A., Reiner, O., Richards, S., Victoria, M.F., Zhang, F.P., et al., 1991. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65, 905-914.
    Verlaan, D.J., Berlivet, S., Hunninghake, G.M., Madore, A.M., Lariviere, M., Moussette, S., Grundberg, E., Kwan, T., Ouimet, M., Ge, B., et al., 2009. Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease. Am. J. Hum. Genet. 85, 377-393.
    Villiger, L., Grisch-Chan, H.M., Lindsay, H., Ringnalda, F., Pogliano, C.B., Allegri, G., Fingerhut, R., Haberle, J., Matos, J., Robinson, M.D., et al., 2018. Treatment of a metabolic liver disease by in vivo genome base editing in adult mice. Nat. Med. 24, 1519-1525.
    Visel, A., Minovitsky, S., Dubchak, I., Pennacchio, L.A., 2007. VISTA Enhancer Browser--a database of tissue-specific human enhancers. Nucleic Acids Res. 35, D88-D92.
    Visscher, P.M., Wray, N.R., Zhang, Q., Sklar, P., McCarthy, M.I., Brown, M.A., Yang, J., 2017. 10 Years of GWAS Discovery: Biology, Function, and Translation. Am. J. Hum. Genet. 101, 5-22.
    Vosa, U., Claringbould, A., Westra, H.J., Bonder, M.J., Deelen, P., Zeng, B., Kirsten, H., Saha, A., Kreuzhuber, R., Yazar, S., et al., 2021. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat. Genet. 53, 1300-1310.
    Walker, R.L., Ramaswami, G., Hartl, C., Mancuso, N., Gandal, M.J., de la Torre-Ubieta, L., Pasaniuc, B., Stein, J.L., Geschwind, D.H., 2019. Genetic Control of Expression and Splicing in Developing Human Brain Informs Disease Mechanisms. Cell 179, 750-771.
    Walsh, N.C., Kenney, L.L., Jangalwe, S., Aryee, K.E., Greiner, D.L., Brehm, M.A., Shultz, L.D., 2017. Humanized Mouse Models of Clinical Disease. Annu. Rev. Pathol. 12, 187-215.
    Wang, G., Sarkar, A., Carbonetto, P., Stephens, M., 2020. A simple new approach to variable selection in regression, with application to genetic fine mapping. J. R. Stat. Soc. Series B Stat. Methodol. 82, 1273-1300.
    Wang, J., Zhu, S., Meng, N., He, Y., Lu, R., Yan, G.R., 2019. ncRNA-Encoded Peptides or Proteins and Cancer. Mol. Ther. 27, 1718-1725.
    Wang, K., Long, B., Liu, F., Wang, J.X., Liu, C.Y., Zhao, B., Zhou, L.Y., Sun, T., Wang, M., Yu, T., et al., 2016. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur. Heart J. 37, 2602-2611.
    Wang, T., Antonacci-Fulton, L., Howe, K., Lawson, H.A., Lucas, J.K., Phillippy, A.M., Popejoy, A.B., Asri, M., Carson, C., Chaisson, M.J.P., et al., 2022. The Human Pangenome Project: a global resource to map genomic diversity. Nature 604, 437-446.
    Wang, X., Raghavan, A., Peters, D.T., Pashos, E.E., Rader, D.J., Musunuru, K., 2018. Interrogation of the atherosclerosis-associated SORT1 (Sortilin 1) locus with primary human hepatocytes, induced pluripotent stem cell-hepatocytes, and locus-humanized mice. Arterioscler Thromb Vasc. Biol. 38, 76-82.
    Wang, Y., Zhang, X., Liu, H., Zhou, X., 2021. Chemical methods and advanced sequencing technologies for deciphering mRNA modifications. Chem. Soc. Rev. 50, 13481-13497.
    Waszak, S.M., Delaneau, O., Gschwind, A.R., Kilpinen, H., Raghav, S.K., Witwicki, R.M., Orioli, A., Wiederkehr, M., Panousis, N.I., Yurovsky, A., et al., 2015. Population variation and genetic control of modular chromatin architecture in humans. Cell 162, 1039-1050.
    Wen, L., Tang, F., 2022. Recent advances in single-cell sequencing technologies. Precis Clin. Med. 5, pbac002.
    Wheeler, E.C., Vora, S., Mayer, D., Kotini, A.G., Olszewska, M., Park, S.S., Guccione, E., Teruya-Feldstein, J., Silverman, L., Sunahara, R.K., et al., 2022. Integrative RNA-omics discovers GNAS alternative splicing as a phenotypic driver of splicing factor-mutant neoplasms. Cancer Discov. 12, 836-855.
    Wheeler, M.A., Clark, I.C., Tjon, E.C., Li, Z., Zandee, S.E.J., Couturier, C.P., Watson, B.R., Scalisi, G., Alkwai, S., Rothhammer, V., et al., 2020. MAFG-driven astrocytes promote CNS inflammation. Nature 578, 593-599.
    Wilk, G., Braun, R., 2018. regQTLs: Single nucleotide polymorphisms that modulate microRNA regulation of gene expression in tumors. PLoS Genet. 14, e1007837.
    Witt, H., 2003. Chronic pancreatitis and cystic fibrosis. Gut 52, ii31-ii41.
    Wolter, J.M., Mao, H., Fragola, G., Simon, J.M., Krantz, J.L., Bazick, H.O., Oztemiz, B., Stein, J.L., Zylka, M.J., 2020. Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA. Nature 587, 281-284.
    Wu, Y., Qi, T., Wray, N.R., Visscher, P.M., Zeng, J., Yang, J., 2023. Joint analysis of GWAS and multi-omics QTL summary statistics reveals a large fraction of GWAS signals shared with molecular phenotypes. Cell Genom. 3, 100344.
    Wu, Y., Zheng, Z., Visscher, P.M., Yang, J., 2017. Quantifying the mapping precision of genome-wide association studies using whole-genome sequencing data. Genome Biol. 18, 86.
    Xi, J., Xu, Y., Guo, Z., Li, J., Wu, Y., Sun, Q., Wang, Y., Chen, M., Zhu, S., Bian, S., et al., 2022. LncRNA SOX1-OT V1 acts as a decoy of HDAC10 to promote SOX1-dependent hESC neuronal differentiation. EMBO Rep. 23, e53015.
    Yanchus, C., Drucker, K.L., Kollmeyer, T.M., Tsai, R., Winick-Ng, W., Liang, M., Malik, A., Pawling, J., De Lorenzo, S.B., Ali, A., et al., 2022. A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation. Science 378, 68-78.
    Yang, C., Zhou, Y., Song, Y., Wu, D., Zeng, Y., Nie, L., Liu, P., Zhang, S., Chen, G., Xu, J., et al., 2023. The complete and fully-phased diploid genome of a male Han Chinese. Cell Res. 33, 745-761.
    Yang, J., Ferreira, T., Morris, A.P., Medland, S.E., Genetic Investigation of, A.T.C., Replication, D.I.G., Meta-analysis, C., Madden, P.A., Heath, A.C., Martin, N.G., et al., 2012. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 44, 369-375.
    Yang, J., Zhang, L., Li, Y., Chen, M., 2022. Identifying key m(6)A-methylated lncRNAs and genes associated with neural tube defects via integrative MeRIP and RNA sequencing analyses. Front. Genet. 13, 974357.
    Yao, H., Gao, C.C., Zhang, D., Xu, J., Song, G., Fan, X., Liang, D.B., Chen, Y.S., Li, Q., Guo, Y., et al., 2023. scm(6)A-seq reveals single-cell landscapes of the dynamic m(6)A during oocyte maturation and early embryonic development. Nat. Commun. 14, 315.
    Yin, Z., Herron, S., Silveira, S., Kleemann, K., Gauthier, C., Mallah, D., Cheng, Y., Margeta, M.A., Pitts, K.M., Barry, J.L., et al., 2023. Identification of a protective microglial state mediated by miR-155 and interferon-gamma signaling in a mouse model of Alzheimer's disease. Nat. Neurosci. 26, 1196-1207.
    Yu, L., Zhou, B., Zhu, Y., Li, L., Zhong, Y., Zhu, L., Wang, H., Chen, H., Xu, J., Guo, T., et al., 2023. HSF1 promotes CD69(+) Treg differentiation to inhibit colitis progression. Theranostics 13, 1892-1905.
    Zeggini, E., Scott, L.J., Saxena, R., Voight, B.F., Marchini, J.L., Hu, T., de Bakker, P.I., Abecasis, G.R., Almgren, P., Andersen, G., et al., 2008. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40, 638-645.
    Zhang, K., Hocker, J.D., Miller, M., Hou, X., Chiou, J., Poirion, O.B., Qiu, Y., Li, Y.E., Gaulton, K.J., Wang, A., et al., 2021. A single-cell atlas of chromatin accessibility in the human genome. Cell 184, 5985-6001.
    Zhang, M., Zhao, K., Xu, X., Yang, Y., Yan, S., Wei, P., Liu, H., Xu, J., Xiao, F., Zhou, H., et al., 2018. A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma. Nat. Commun. 9, 4475.
    Zhao, Y., Alexandrov, P.N., Jaber, V., Lukiw, W.J., 2016. Deficiency in the ubiquitin conjugating enzyme UBE2A in Alzheimer's disease (AD) is linked to deficits in a natural circular miRNA-7 sponge (circRNA; ciRS-7). Genes (Basel) 7, 116.
    Zhao, X., Bhattacharyya, A., 2018. Human Models Are Needed for Studying Human Neurodevelopmental Disorders. Am. J. Hum. Genet. 103, 829-857.
    Zheng, J., Haberland, V., Baird, D., Walker, V., Haycock, P.C., Hurle, M.R., Gutteridge, A., Erola, P., Liu, Y., Luo, S., et al., 2020. Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases. Nat. Genet. 52, 1122-1131.
    Zhou, J., Troyanskaya, O.G., 2015. Predicting effects of noncoding variants with deep learning-based sequence model. Nat. Methods 12, 931-934.
    Zhu, Z., Zhang, F., Hu, H., Bakshi, A., Robinson, M.R., Powell, J.E., Montgomery, G.W., Goddard, M.E., Wray, N.R., Visscher, P.M., et al., 2016. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat. Genet. 48, 481-487.
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