Longitudinal SNP-set association analysis of quantitative phenotypes

Genetic Epidemiology
Zhong WangZuoheng Wang

Abstract

Many genetic epidemiological studies collect repeated measurements over time. This design not only provides a more accurate assessment of disease condition, but allows us to explore the genetic influence on disease development and progression. Thus, it is of great interest to study the longitudinal contribution of genes to disease susceptibility. Most association testing methods for longitudinal phenotypes are developed for single variant, and may have limited power to detect association, especially for variants with low minor allele frequency. We propose Longitudinal SNP-set/sequence kernel association test (LSKAT), a robust, mixed-effects method for association testing of rare and common variants with longitudinal quantitative phenotypes. LSKAT uses several random effects to account for the within-subject correlation in longitudinal data, and allows for adjustment for both static and time-varying covariates. We also present a longitudinal trait burden test (LBT), where we test association between the trait and the burden score in linear mixed models. In simulation studies, we demonstrate that LBT achieves high power when variants are almost all deleterious or all protective, while LSKAT performs well in a wide range of geneti...Continue Reading

References

Jul 24, 2004·American Journal of Human Genetics·Benjamin M Neale, Pak C Sham
Oct 28, 2005·Genome Research·Stephen F SchaffnerDavid Altshuler
Aug 19, 2007·Nature Reviews. Genetics·Timothy M Frayling
Feb 14, 2009·PLoS Genetics·Bo Eskerod Madsen, Sharon R Browning
Oct 8, 2009·Genetic Epidemiology·Andrew P Morris, Eleftheria Zeggini
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher
May 18, 2010·American Journal of Human Genetics·Alkes L PriceShamil R Sunyaev
May 19, 2010·Nature Reviews. Genetics·Evan E EichlerJoseph H Nadeau
Jun 22, 2010·American Journal of Human Genetics·Michael C WuXihong Lin
Sep 8, 2010·Journal of the American Medical Informatics Association : JAMIA·Iftikhar J KulloChristopher G Chute
Feb 5, 2011·Human Genetics·Kiranmoy DasRongling Wu
Mar 17, 2011·PLoS Genetics·Benjamin M NealeMark J Daly
Jul 9, 2011·American Journal of Human Genetics·Michael C WuXihong Lin
Sep 3, 2011·American Journal of Human Genetics·Dan-Yu Lin, Zheng-Zheng Tang
May 15, 2012·Genetic Epidemiology·Nicholas A FurlotteSusana Eyheramendy
May 15, 2012·Journal of the Royal Statistical Society. Series C, Applied Statistics·Yuanjia WangRunze Li
Jun 16, 2012·Biostatistics·Seunggeun LeeXihong Lin
Jul 26, 2012·International Journal of Obesity : Journal of the International Association for the Study of Obesity·L GoumidiA Meirhaeghe
Aug 23, 2012·Statistics in Medicine·Karolina SikorskaEmmanuel Lesaffre
Oct 25, 2012·European Journal of Human Genetics : EJHG·Osorio D MeirellesDavid Schlessinger
Jan 3, 2013·Genetic Epidemiology·Han ChenJosée Dupuis
Mar 2, 2013·Human Molecular Genetics·Diana L CousminerUNKNOWN Early Growth Genetics (EGG) Consortium
Mar 19, 2013·Statistical Applications in Genetics and Molecular Biology·Douglas LondonoDerek Gordon
Jun 8, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Omri GottesmanUNKNOWN eMERGE Network
Aug 13, 2014·Genetic Epidemiology·Joseph Beyene, Jemila S Hamid
Aug 13, 2014·Genetic Epidemiology·Zheyang WuPhillip E Melton
Jan 20, 2016·Genetic Epidemiology·Li-Chu ChienYen-Feng Chiu

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