Retrospective Association Analysis of Longitudinal Binary Traits Identifies Important Loci and Pathways in Cocaine Use.

Weimiao WuZuoheng Wang


Longitudinal phenotypes have been increasingly available in genome-wide association studies (GWAS) and electronic health record-based studies for identification of genetic variants that influence complex traits over time. For longitudinal binary data, there remain significant challenges in gene mapping, including misspecification of the model for phenotype distribution due to ascertainment. Here, we propose L-BRAT (Longitudinal Binary-trait Retrospective Association Test), a retrospective, generalized estimating equation-based method for genetic association analysis of longitudinal binary outcomes. We also develop RGMMAT, a retrospective, generalized linear mixed model-based association test. Both tests are retrospective score approaches in which genotypes are treated as random conditional on phenotype and covariates. They allow both static and time-varying covariates to be included in the analysis. Through simulations, we illustrated that retrospective association tests are robust to ascertainment and other types of phenotype model misspecification, and gain power over previous association methods. We applied L-BRAT and RGMMAT to a genome-wide association analysis of repeated measures of cocaine use in a longitudinal cohort. P...Continue Reading


Oct 5, 2001·Nature Reviews. Neuroscience·S E Hyman, R C Malenka
Feb 5, 2005·Molecular and Cellular Neurosciences·Amine Bahi, Jean-Luc Dreyer
May 18, 2005·Drug and Alcohol Dependence·Amira Pierucci-LaghaHenry R Kranzler
Oct 28, 2005·Genome Research·Stephen F SchaffnerDavid Altshuler
Apr 6, 2006·Molecular Pharmacology·Amy K JassenBertha K Madras
Jul 20, 2006·Medical Care·Amy C JusticeKendall Bryant
Mar 29, 2008·Biostatistics·Jonathan S Schildcrout, Patrick J Heagerty
Oct 1, 2009·Physiological Reviews·Julie Le MerrerBrigitte L Kieffer
Feb 5, 2011·Human Genetics·Kiranmoy DasRongling Wu
Sep 17, 2011·Genetic Epidemiology·Baiyu ZhouAlice S Whittemore
May 15, 2012·Genetic Epidemiology·Nicholas A FurlotteSusana Eyheramendy
Aug 23, 2012·Statistics in Medicine·Karolina SikorskaEmmanuel Lesaffre
Oct 25, 2012·European Journal of Human Genetics : EJHG·Osorio D MeirellesDavid Schlessinger
Mar 19, 2013·Statistical Applications in Genetics and Molecular Biology·Douglas LondonoDerek Gordon
May 7, 2013·American Journal of Human Genetics·Johanna Jakobsdottir, Mary Sara McPeek
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Oct 10, 2014·Statistics in Medicine·Colleen M SitlaniBruce M Psaty
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Jul 23, 2015·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Fernando S GoesAnn E Pulver
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