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Volume 36 Issue 12
Dec.  2009
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Bivariate association analysis for quantitative traits using generalized estimation equation

doi: 10.1016/S1673-8527(08)60166-6
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  • Corresponding author: E-mail address: hwdeng@hunnu.edu.cn (Hongwen Deng)
  • Received Date: 2009-05-25
  • Accepted Date: 2009-11-09
  • Rev Recd Date: 2009-11-09
  • Available Online: 2009-12-21
  • Publish Date: 2009-12-20
  • Quantitative traits often underlie risk for complex diseases. Many studies collect multiple correlated quantitative phenotypes and perform univariate analyses on each of them respectively. However, this strategy may not be powerful and has limitations to detect pleiotropic genes that may underlie correlated quantitative traits. In addition, testing multiple traits individually will exacerbate perplexing problem of multiple testing. In this study, generalized estimating equation 2 (GEE2) is applied to association mapping of two correlated quantitative traits. We suppose that a quantitative trait locus is located in a chromosome region that exerts pleiotropic effects on multiple quantitative traits. In that region, multiple SNPs are genotyped. Genotypes of these SNPs and the two quantitative traits affected by a causal SNP were simulated under various parameter values: residual correlation coefficient between two traits, causal SNP heritability, minor allele frequency of the causal SNP, extent of linkage disequilibrium with the causal SNP, and the test sample size. By power analytical analyses, it is showed that the bivariate method is generally more powerful than the univariate method. This method is robust and yields false-positive rates close to the pre-set nominal significance level. Our real data analyses attested to the usefulness of the method.
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  • [1]
    Amos, C.I., Laing, A.E. A comparison of univariate and multivariate tests for genetic linkage Genet. Epidemiol., 10 (1993),pp. 671-676
    [2]
    Deng, F.Y., Xiao, P., Lei, S.F. et al. Bivariate whole genome linkage analysis for femoral neck geometric parameters and total body lean mass J. Bone Miner. Res., 22 (2007),pp. 808-816
    [3]
    Hedrick, P., Kumar, S. Mutation and linkage disequilibrium in human mtDNA Eur. J. Hum. Genet., 9 (2001),pp. 969-972
    [4]
    Hui, S.L., Slemenda, C.W., Baseline measurement of bone mass predicts fracture in white women Ann. Intern. Med., 111 (1989),pp. 355-361
    [5]
    Jiang, C., Zeng, Z.B. Multiple trait analysis of genetic mapping for quantitative trait loci Genetics, 140 (1995),pp. 1111-1127
    [6]
    Karasik, D., Dupuis, J., Cupples, L.A. et al. Bivariate linkage study of proximal hip geometry and body size indices: The Framingham study Calcif. Tissue Int., 81 (2007),pp. 162-173
    [7]
    Kessler, R.C., Berglund, P., Demler, O. et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication Arch. Gen. Psychiatry, 62 (2005),pp. 593-602
    [8]
    Khaodhiar, L., McCowen, K.C., Blackburn, G.L. Obesity and its comorbid conditions Clin. Cornerstone., 2 (1999),pp. 17-31
    [9]
    Lange, C., Laird, N.M. On a general class of conditional tests for family-based association studies in genetics: The asymptotic distribution, the conditional power, and optimality considerations. Genet. Epidemiol., 23 (2002),pp. 165-180
    [10]
    Lange, C., Silverman, E.K., Xu, X. et al. A multivariate family-based association test using generalized estimating equations: FBAT-GEE Biostatistics, 4 (2003),pp. 195-206
    [11]
    Lange, C., Whittaker, J.C. Mapping quantitative trait Loci using generalized estimating equations Genetics, 159 (2001),pp. 1325-1337
    [12]
    Liang, K.Y., Zeger, S.L. Longitudinal data analysis using generalized linear models Biometrika, 73 (1986),pp. 13-22
    [13]
    Lin, S., Chakravarti, A., Cutler, D.J. Exhaustive allelic transmission disequilibrium tests as a new approach to genome-wide association studies Nat. Genet., 36 (2004),pp. 1181-1188
    [14]
    Liu, J.F., Pei, Y.F., Papasian, C.J. et al. Bivariate association analyses for the mixture of continuous and binary traits with the use of extended generalized estimating equations Genet. Epidemiol., 33 (2009),pp. 217-227
    [15]
    Martinez, F.D., Graves, P.E., Baldini, M. et al. Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing J. Clin. Invest, 100 (1997),pp. 3184-3188
    [16]
    Nyholt, D.R. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other Am. J. Hum. Genet., 74 (2004),pp. 765-769
    [17]
    Pei, Y.F., Zhang, L., Liu, J.F. et al. Multivariate association test using haplotype trend regression Ann. Hum. Genet., 73 (2009),pp. 456-464
    [18]
    Price, A.L., Patterson, N.J., Plenge, R.M. et al. Principal components analysis corrects for stratification in genome-wide association studies Nat. Genet., 38 (2006),pp. 904-909
    [19]
    Pritchard, J.K., Stephens, M., Donnelly, P. Inference of population structure using multilocus genotype data Genetics, 155 (2000),pp. 945-959
    [20]
    R Development Core Team (2005). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria, ISBN 3-900051-07-0.
    [21]
    Stephens, M., Smith, N.J., Donnelly, P. A new statistical method for haplotype reconstruction from population data Am. J. Hum. Genet., 68 (2001),pp. 978-989
    [22]
    Tang, Z.H., Xiao, P., Lei, S.F. et al. A bivariate whole-genome linkage scan suggests several shared genomic regions for obesity and osteoporosis J. Clin. Endocrinol. Metab., 92 (2007),pp. 2751-2757
    [23]
    Turki, J., Pak, J., Green, S.A. et al. Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype J. Clin. Invest., 95 (1995),pp. 1635-1641
    [24]
    Yan, J. The R Package geepack for Generalized Estimating Equations J. Stat. Softw., 15 (2006),pp. 1-11
    [25]
    Zeger, S.L., Liang, K.Y., Albert, P.S. Models for longitudinal data: A generalized estimating equation approach Biometrics, 44 (1988),pp. 1049-1060
    [26]
    Zhao, L.P., Prentice, R.L. Correlated binary regression using a quadratic exponential model Biometrika, 77 (1990),pp. 642-648
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