A genome wide association study between copy number variation (CNV) and human height in Chinese population

Xi Li; Lijun Tan; Xiaogang Liu; Shufeng Lei; Tielin Yang; Xiangding Chen; Fang Zhang; Yue Fang; Yan Guo; Liang Zhang; Han Yan; Feng Pan; Zhixin Zhang; Yumei Peng; Qi Zhou; Lina He; Xuezhen Zhu; Jing Cheng; Lishu Zhang; Yaozhong Liu; Qing Tian; Hongwen Deng

doi:10.1016/S1673-8527(09)60095-3

Volume 37 Issue 12

Dec. 2010

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Article Navigation > Journal of Genetics and Genomics > 2010 > 37(12): 779-785

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A genome wide association study between copy number variation (CNV) and human height in Chinese population

doi: 10.1016/S1673-8527(09)60095-3

a
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China
b
The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
c
National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China
d
Department of Basic Medical Science and Orthopedic Surgery, School of Medicine, University of Missouri - Kansas City, Kansas City, MO 64108, USA
e
College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China

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Corresponding author: E-mail address: dengh@umkc.edu (Hongwen Deng)
Received Date: 2010-05-07
Accepted Date: 2010-10-29
Rev Recd Date: 2010-10-27

Available Online: 2010-12-28

Publish Date: 2010-12-20

Abstract

Abstract

Copy number variation (CNV) is a type of genetic variation which may have important roles in phenotypic variability and disease susceptibility. To hunt for genetic variants underlying human height variation, we performed a genome wide CNV association study for human height in 618 Chinese unrelated subjects using Affymetrix 500K array set. After adjusting for age and sex, we found that four CNVs at 6p21.3, 8p23.3-23.2, 9p23 and 16p12.1 were associated with human height (with borderline significant p value: 0.013, 0.011, 0.024, 0.049; respectively). However, after multiple tests correction, none of them was associated with human height. We observed that the gain of copy number (more than 2 copies) at 8p23.3-23.2 was associated with lower height (normal copy number vs. gain of copy number: 161.2 cm vs. 153.7 cm, p = 0.011), which accounted for 0.9% of height variation. Loss of copy number (less than 2 copies) at 6p21.3 was associated with 0.8% lower height (loss of copy numbervs. normal copy number: 154.5 cm vs. 161.1 cm, p = 0.013). Since no important genes influencing height located in CNVs at loci of 8p23.3-23.2 and 6p21.3, the two CNVs may cause the structural rearrangements of neighbored important candidate genes, thus regulates the variation of height. Our results expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height.
- CNV,
- human height,
- GWAS,
- Affymetrix 500K array

These authors contributed equally to this study.

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References(37)

References

[1]	Ball, S.E., McGuckin, C.P., Jenkins, G. et al. Diamond-Blackfan anaemia in the U.K.: analysis of 80 cases from a 20-year birth cohort Br. J. Haematol., 94 (1996),pp. 645-653
[2]	Boniotto, M., Ventura, M., Eskdale, J. et al. Genet. Test, 8 (2004),pp. 325-327
[3]	Buckland, P.R. Polymorphically duplicated genes: their relevance to phenotypic variation in humans Ann. Med., 35 (2003),pp. 308-315
[4]	Carmichael, C.M., McGue, M. A cross-sectional examination of height, weight, and body mass index in adult twins J. Gerontol. A Biol. Sci. Med. Sci., 50 (1995),pp. B237-B244
[5]	Di, X., Matsuzaki, H., Webster, T.A. et al. Dynamic model based algorithms for screening and genotyping over 100 K SNPs on oligonucleotide microarrays Bioinformatics, 21 (2005),pp. 1958-1963
[6]	Ducy, P., Zhang, R., Geoffroy, V. et al. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation Cell, 89 (1997),pp. 747-754
[7]	Fanciulli, M., Norsworthy, P.J., Petretto, E. et al. Nat. Genet., 39 (2007),pp. 721-723
[8]	Fang, Y., van Meurs, J.B., Rivadeneira, F. et al. Vitamin D receptor gene haplotype is associated with body height and bone size J. Clin. Endocrinol. Metab., 92 (2007),pp. 1491-1501
[9]	Feuk, L., Carson, A.R., Scherer, S.W. Structural variation in the human genome Nat. Rev. Genet., 7 (2006),pp. 85-97
[10]	Freeman, J.L., Perry, G.H., Feuk, L. et al. Copy number variation: new insights in genome diversity Genome Res., 16 (2006),pp. 949-961
[11]	Gazda, H., Lipton, J.M., Willig, T.N. et al. Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease Blood, 97 (2001),pp. 2145-2150
[12]	Gojic, V., van't Veer-Korthof, E.T., Bosch, L.J. et al. Congenital hypoplastic anemia: another example of autosomal dominant transmission Am. J. Med. Genet., 50 (1994),pp. 87-89
[13]	Gudbjartsson, D.F., Walters, G.B., Thorleifsson, G. et al. Many sequence variants affecting diversity of adult human height Nat. Genet., 40 (2008),pp. 609-615
[14]	Jensen, B.L. Somatic development in cleidocranial dysplasia Am. J. Med. Genet., 35 (1990),pp. 69-74
[15]	Kalinicheva, V.I. Congenital hypoplastic anemia with selective disorder of the erythroid process (Blackfan-Diamond anemia) Pediatriia, 51 (1972),pp. 58-62
[16]	Kimura, T., Cheah, K.S., Chan, S.D. et al. The human alpha 2(XI) collagen (COL11A2) chain. Molecular cloning of cDNA and genomic DNA reveals characteristics of a fi-brillar collagen with differences in genomic organization J. Biol. Chem., 264 (1989),pp. 13910-13916
[17]	Komura, D., Shen, F., Ishikawa, S. et al. Genome-wide detection of human copy number variations using high-density DNA oligonucleotide arrays Genome Res., 16 (2006),pp. 1575-1584
[18]	Lettre, G., Jackson, A.U., Gieger, C. et al. Identification of ten loci associated with height highlights new biological pathways in human growth Nat. Genet., 40 (2008),pp. 584-591
[19]	Luo, Z.C., Albertsson-Wikland, K., Karlberg, J. Target height as predicted by parental heights in a population-based study Pediatr. Res., 44 (1998),pp. 563-571
[20]	McCarroll, S.A., Hadnott, T.N., Perry, G.H. et al. Common deletion polymorphisms in the human genome Nat. Genet., 38 (2006),pp. 86-92
[21]	Merla, G., Howald, C., Henrichsen, C.N. et al. Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes Am. J. Hum. Genet., 79 (2006),pp. 332-341
[22]	Nance, W.E., Sweeney, A. A recessively inherited chondro-dystrophy Birth Defects Orig. Artic. Ser., 6 (1970),pp. 25-27
[23]	Nguyen, D.Q., Webber, C., Ponting, C.P. Bias of selection on human copy-number variants PLoS Genet., 2 (2006),p. e20
[24]	Phillips, K., Quantitative genetic analysis of longitudinal trends in height: preliminary results from the Louisville Twin Study Acta Genet. Med. Gemellol. (Roma), 39 (1990),pp. 143-163
[25]	Pritchard, J.K., Stephens, M., Donnelly, P. Inference of population structure using multilocus genotype data Genetics., 155 (2000),pp. 945-959
[26]	Rabbee, N., Speed, T.P. A genotype calling algorithm for affymetrix SNP arrays Bioinformatics, 22 (2006),pp. 7-12
[27]	Redon, R., Ishikawa, S., Fitch, K.R. et al. Global variation in copy number in the human genome Nature, 444 (2006),pp. 444-454
[28]	Shao, W., Tang, J., Song, W. et al. Genes Immun., 8 (2007),pp. 224-231
[29]	Stein, G.S., Lian, J.B., van Wijnen, A.J. et al. Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression Oncogene, 23 (2004),pp. 4315-4329
[30]	Storey, J.D. A direct approach to false discovery rates J. R. Stat. Soc. Ser. B-Stat. Methodol., 64 (2002),pp. 479-498
[31]	Storey, J.D., Tibshirani, R. Statistical significance for ge-nomewide studies Proc. Natl. Acad. Sci. USA, 100 (2003),pp. 9440-9445
[32]	Stranger, B.E., Forrest, M.S., Dunning, M. et al. Relative impact of nu-cleotide and copy number variation on gene expression phenotypes Science, 315 (2007),pp. 848-853
[33]	Temtamy, S.A., Mannikko, M., Abdel-Salam, G.M. et al. Oto-spondylo-megaepiphyseal dysplasia (OSMED): clinical and radiological findings in sibs homozygous for premature stop codon mutation in the COL11A2 gene Am. J. Med. Genet. A, 140 (2006),pp. 1189-1195
[34]	Weedon, M.N., Lango, H., Lindgren, C.M. et al. Genome-wide association analysis identifies 20 loci that influence adult height Nat. Genet., 40 (2008),pp. 57-583
[35]	Willig, T.N., Draptchinskaia, N., Dianzani, I. et al. Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression Blood, 94 (1999),pp. 4294-4306
[36]	Yang, F., Lv, J.H., Lei, S.F. et al. Receiver-operating characteristic analyses of body mass index, waist circumference and waist-to-hip ratio for obesity: screening in young adults in central south of China Clinical Nutrition., 25 (2006),pp. 1030-1039
[37]	Yu, V.C., Delsert, C., Andersen, B. et al. RXR beta: a coregulator that enhances binding of reti-noic acid, thyroid hormone, and vitamin D receptors to their cognate response elements Cell, 67 (1991),pp. 1251-1266