FLAGS: A Flexible and Adaptive Association Test for Gene Sets Using Summary Statistics

Genetics
Jianfei HuangShizhong Han

Abstract

Genome-wide association studies (GWAS) have been widely used for identifying common variants associated with complex diseases. Despite remarkable success in uncovering many risk variants and providing novel insights into disease biology, genetic variants identified to date fail to explain the vast majority of the heritability for most complex diseases. One explanation is that there are still a large number of common variants that remain to be discovered, but their effect sizes are generally too small to be detected individually. Accordingly, gene set analysis of GWAS, which examines a group of functionally related genes, has been proposed as a complementary approach to single-marker analysis. Here, we propose a FL: exible and A: daptive test for G: ene S: ets (FLAGS), using summary statistics. Extensive simulations showed that this method has an appropriate type I error rate and outperforms existing methods with increased power. As a proof of principle, through real data analyses of Crohn's disease GWAS data and bipolar disorder GWAS meta-analysis results, we demonstrated the superior performance of FLAGS over several state-of-the-art association tests for gene sets. Our method allows for the more powerful application of gene s...Continue Reading

References

Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Feb 17, 2007·Bioinformatics·Jelle J Goeman, Peter Bühlmann
Jun 8, 2007·Nature·UNKNOWN Wellcome Trust Case Control Consortium
Aug 19, 2007·Nature Reviews. Immunology·Stefan Feske
Oct 30, 2007·American Journal of Human Genetics·Kai WangMaja Bucan
Apr 10, 2008·Nature Reviews. Genetics·Mark I McCarthyJoel N Hirschhorn
Aug 30, 2008·Genomics·Ali TorkamaniNicholas J Schork
Dec 18, 2008·Nature Immunology·Monika Vig, Jean-Pierre Kinet
Mar 3, 2009·American Journal of Human Genetics·Kai WangHakon Hakonarson
Jun 23, 2009·American Journal of Human Genetics·Peter HolmansNick Craddock
Jul 22, 2009·Bioinformatics·Colm O'DushlaineAiden Corvin
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher
Nov 3, 2009·Nucleic Acids Research·Minoru KanehisaMika Hirakawa
Jun 22, 2010·American Journal of Human Genetics·Lin S ChenLi Hsu
Jun 22, 2010·American Journal of Human Genetics·Michael C WuXihong Lin
Jul 6, 2010·American Journal of Human Genetics·Jimmy Z LiuStuart Macgregor
Nov 19, 2010·Nature Reviews. Genetics·Kai WangHakon Hakonarson
Sep 20, 2011·Nature Genetics·UNKNOWN Psychiatric GWAS Consortium Bipolar Disorder Working Group
Nov 12, 2013·Current Opinion in Genetics & Development·Nir AtiasRoded Sharan
May 17, 2014·Genetics·Wei PanPeng Wei
Aug 27, 2014·Trends in Genetics : TIG·Michael A MooneyBeth Wilmot
Dec 4, 2014·Trends in Genetics : TIG·Dan Chen, Ulf Gyllensten
Apr 18, 2015·PLoS Computational Biology·Christiaan A de LeeuwDanielle Posthuma
Jun 30, 2015·American Journal of Human Genetics·Wei PanPeng Wei

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bipolar Disorder

Bipolar disorder is characterized by manic and/or depressive episodes and associated with uncommon shifts in mood, activity levels, and energy. Discover the latest research this illness here.