Variance component model to account for sample structure in genome-wide association studies

Nature Genetics
Hyun Min KangEleazar Eskin

Abstract

Although genome-wide association studies (GWASs) have identified numerous loci associated with complex traits, imprecise modeling of the genetic relatedness within study samples may cause substantial inflation of test statistics and possibly spurious associations. Variance component approaches, such as efficient mixed-model association (EMMA), can correct for a wide range of sample structures by explicitly accounting for pairwise relatedness between individuals, using high-density markers to model the phenotype distribution; but such approaches are computationally impractical. We report here a variance component approach implemented in publicly available software, EMMA eXpedited (EMMAX), that reduces the computational time for analyzing large GWAS data sets from years to hours. We apply this method to two human GWAS data sets, performing association analysis for ten quantitative traits from the Northern Finland Birth Cohort and seven common diseases from the Wellcome Trust Case Control Consortium. We find that EMMAX outperforms both principal component analysis and genomic control in correcting for sample structure.

References

May 23, 1998·American Journal of Human Genetics·A S Whittemore, I P Tu
Aug 3, 1999·Genetics·M Lynch, K Ritland
Mar 11, 2000·American Journal of Human Genetics·M S McPeek, L Sun
May 29, 2000·American Journal of Human Genetics·J K PritchardP Donnelly
Oct 18, 2000·American Journal of Human Genetics·M P EpsteinM Boehnke
Apr 21, 2001·Biometrics·B Devlin, K Roeder
Oct 9, 2001·American Journal of Human Genetics·C OberM S McPeek
Oct 9, 2001·American Journal of Human Genetics·D L NewmanN J Cox
Jan 5, 2002·Genetic Epidemiology·Silviu-Alin BacanuKathryn Roeder
Mar 29, 2003·Genetics·Brook G Milligan
Jun 3, 2004·Current Opinion in Genetics & Development·Teppo Varilo, Leena Peltonen
Dec 21, 2004·Nature Genetics·Agnar HelgasonKári Stefánsson
Mar 29, 2005·Nature Genetics·Jonathan MarchiniLon R Cardon
Apr 23, 2005·Nature Methods·Rafael A IrizarryWayne Yu
Sep 10, 2005·PLoS Genetics·Benjamin F Voight, Jonathan K Pritchard
Aug 29, 2006·PLoS Genetics·Giuseppe PiliaDavid Schlessinger
Sep 20, 2006·Nature Reviews. Genetics·Bruce S WeirAmanda B Hepler
Sep 28, 2006·PLoS Genetics·David M EvansLon R Cardon
Dec 30, 2006·PLoS Genetics·Nick PattersonDavid Reich
Jan 24, 2007·PLoS Genetics·Keyan ZhaoMagnus Nordborg
May 29, 2007·Nature·Douglas F EastonBruce A J Ponder
Jun 8, 2007·Nature·UNKNOWN Wellcome Trust Case Control Consortium
Aug 2, 2007·American Journal of Human Genetics·Timothy Thornton, Mary Sara McPeek
Oct 10, 2007·American Journal of Human Genetics·Wei-Min Chen, Goncalo R Abecasis
Nov 16, 2007·Nature·Sergey NejentsevUNKNOWN Wellcome Trust Case Control Consortium
Feb 27, 2008·Genetic Epidemiology·Frank Dudbridge, Arief Gusnanto
Apr 22, 2008·Nature Genetics·John Novembre, Matthew Stephens
Jul 26, 2008·Nature Nanotechnology
Sep 2, 2008·Nature·John NovembreCarlos D Bustamante
Dec 9, 2008·American Journal of Human Genetics·Eveliina JakkulaLeena Peltonen
Mar 31, 2009·Nature Genetics·Shahana AhmedDouglas F Easton
Apr 1, 2009·Genetic Epidemiology·Yoonha ChoiBruce S Weir
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher

❮ Previous
Next ❯

Citations

Sep 15, 2011·TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik·Minghui WangZewei Luo
Jan 15, 2011·Human Genetics·Marie-Hélène Roy-GagnonDamian Labuda
Aug 2, 2011·Human Genetics·Ani ManichaikulJosyf C Mychaleckyj
Jul 24, 2012·Human Genetics·Noah Zaitlen, Peter Kraft
Sep 7, 2012·Genetics Research·Kathryn E KemperMichael E Goddard
Oct 16, 2012·Development and Psychopathology·Scott I VriezeMatt McGue
Dec 15, 2010·European Journal of Human Genetics : EJHG·Jeroen R HuygheGuy Van Camp
Oct 6, 2011·European Journal of Human Genetics : EJHG·Fumihiko TakeuchiNorihiro Kato
Dec 21, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Brian H ShirtsBrian L Browning
Jun 14, 2013·Heredity·P MarjoramS V Nuzhdin
Aug 13, 2011·Nature·UNKNOWN International Multiple Sclerosis Genetics ConsortiumAlastair Compston
Mar 8, 2013·Nature·Robert J SchmitzJoseph R Ecker
Nov 21, 2013·Nature Communications·Todd LenczAriel Darvasi
May 30, 2012·Nature Genetics·Adam KiezunShamil R Sunyaev
Jun 19, 2012·Nature Genetics·Xiang Zhou, Matthew Stephens
Sep 18, 2012·Nature Genetics·Gulnara R SvishchevaYurii S Aulchenko
Apr 27, 2013·Nature Genetics·Jennifer ListgartenDavid Heckerman
Oct 8, 2013·Nature Genetics·Cristen J WillerUNKNOWN Global Lipids Genetics Consortium
May 10, 2011·Nature Genetics·Jian YangPeter M Visscher
Sep 6, 2011·Nature Methods·Christoph LippertDavid Heckerman
Jun 7, 2012·Nature Methods·Jennifer ListgartenDavid Heckerman
Jun 16, 2010·Nature Reviews. Genetics·Alkes L PriceNick Patterson
Feb 27, 2013·Nature Reviews. Genetics·Jae Hoon Sul, Eleazar Eskin
Feb 27, 2013·Nature Reviews. Genetics·Alkes L PriceNick Patterson
Oct 14, 2010·Nature Reviews. Genetics·Vikas BansalNicholas J Schork
Oct 10, 2012·Nature Reviews. Genetics·Jonathan Flint, Eleazar Eskin
May 10, 2013·Nature Reviews. Genetics·Evangelos Evangelou, John P A Ioannidis
Oct 19, 2013·Nature Reviews. Genetics·Outi SavolainenJuha Merilä
Nov 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yan LiJustin O Borevitz
Jan 11, 2012·Proceedings of the National Academy of Sciences of the United States of America·Neda JahanshadPaul M Thompson
Sep 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Luis BarbozaRubén Alcázar
Sep 17, 2013·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Emrah Kostem, Eleazar Eskin
Oct 12, 2010·Bioinformatics·Ani ManichaikulWei-Min Chen
Jul 17, 2012·Bioinformatics·Alexander E LipkaZhiwu Zhang
Nov 24, 2012·Bioinformatics·Barbara RakitschKarsten Borgwardt

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