Estimating Effects and Making Predictions from Genome-Wide Marker Data

被引:110
作者
Goddard, Michael E. [1 ]
Wray, Naomi R. [2 ]
Verbyla, Klara [1 ]
Visscher, Peter M. [2 ]
机构
[1] Univ Melbourne, Fac Land & Food Resources, Melbourne, Vic 3010, Australia
[2] Queensland Inst Med Res, Brisbane, Qld 4006, Australia
基金
英国医学研究理事会;
关键词
Genome-wide association study; prediction; estimation; LINKAGE DISEQUILIBRIUM; CONFIDENCE-INTERVALS; COMPLEX TRAITS; GENETIC VALUE; HUMAN HEIGHT; ODDS RATIOS; SELECTION; BIAS; ASSOCIATION; MODEL;
D O I
10.1214/09-STS306
中图分类号
O21 [概率论与数理统计]; C8 [统计学];
学科分类号
020208 ; 070103 ; 0714 ;
摘要
In genome-wide association studies (GWAS), hundreds of thousands of genetic markers (SNPs) are tested for association with a trait or phenotype. Reported effects tend to be larger in magnitude than the true effects of these markers, the so-called "winner's curse." We argue that the classical definition of unbiasedness is not useful in this context and propose to use a different definition of unbiasedness that is a property of the estimator we advocate. We suggest an integrated approach to the estimation of the SNP effects and to the prediction of trait values, treating SNP effects as random instead of fixed effects. Statistical methods traditionally used in the prediction of trait values in the genetics of livestock, which predates the availability of SNP data, can be applied to analysis of GWAS, giving better estimates of the SNP effects and predictions of phenotypic and genetic values in individuals.
引用
收藏
页码:517 / 529
页数:13
相关论文
共 56 条
[1]   Bias in estimates of quantitative-trait-locus effect in genome scans: Demonstration of the phenomenon and a method-of-moments procedure for reducing bias [J].
Allison, DB ;
Fernandez, JR ;
Heo, M ;
Zhu, SK ;
Etzel, C ;
Beasley, TM ;
Amos, CI .
AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (03) :575-585
[2]   Multipoint quantitative-trait linkage analysis in general pedigrees [J].
Almasy, L ;
Blangero, J .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 62 (05) :1198-1211
[3]   Predicting human height by Victorian and genomic methods [J].
Aulchenko, Yurii S. ;
Struchalin, Maksim V. ;
Belonogova, Nadezhda M. ;
Axenovich, Tatiana I. ;
Weedon, Michael N. ;
Hofman, Albert ;
Uitterlinden, Andre G. ;
Kayser, Manfred ;
Oostra, Ben A. ;
van Duijn, Cornelia M. ;
Janssens, A. Cecile J. W. ;
Borodin, Pavel M. .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2009, 17 (08) :1070-1075
[4]  
BEAVIS WD, 1988, MOL DISSECTION COMPL, P145
[5]  
Beavis WD, 1994, P 49 ANN CORN SORGH, V250, P266
[6]   Estimating coverage and power for genetic association studies using near-complete variation data [J].
Bhangale, Tushar R. ;
Rieder, Mark J. ;
Nickerson, Deborah A. .
NATURE GENETICS, 2008, 40 (07) :841-843
[7]   Biased estimators of quantitative trait locus heritability and location in interval mapping [J].
Bogdan, M ;
Doerge, RW .
HEREDITY, 2005, 95 (06) :476-484
[8]   Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].
Burton, Paul R. ;
Clayton, David G. ;
Cardon, Lon R. ;
Craddock, Nick ;
Deloukas, Panos ;
Duncanson, Audrey ;
Kwiatkowski, Dominic P. ;
McCarthy, Mark I. ;
Ouwehand, Willem H. ;
Samani, Nilesh J. ;
Todd, John A. ;
Donnelly, Peter ;
Barrett, Jeffrey C. ;
Davison, Dan ;
Easton, Doug ;
Evans, David ;
Leung, Hin-Tak ;
Marchini, Jonathan L. ;
Morris, Andrew P. ;
Spencer, Chris C. A. ;
Tobin, Martin D. ;
Attwood, Antony P. ;
Boorman, James P. ;
Cant, Barbara ;
Everson, Ursula ;
Hussey, Judith M. ;
Jolley, Jennifer D. ;
Knight, Alexandra S. ;
Koch, Kerstin ;
Meech, Elizabeth ;
Nutland, Sarah ;
Prowse, Christopher V. ;
Stevens, Helen E. ;
Taylor, Niall C. ;
Walters, Graham R. ;
Walker, Neil M. ;
Watkins, Nicholas A. ;
Winzer, Thilo ;
Jones, Richard W. ;
McArdle, Wendy L. ;
Ring, Susan M. ;
Strachan, David P. ;
Pembrey, Marcus ;
Breen, Gerome ;
St Clair, David ;
Caesar, Sian ;
Gordon-Smith, Katherine ;
Jones, Lisa ;
Fraser, Christine ;
Green, Elain K. .
NATURE, 2007, 447 (7145) :661-678
[9]  
Casella George, 2021, Statistical inference
[10]   Linkage disequilibrium and persistence of phase in Holstein-Friesian, Jersey and Angus cattle [J].
de Roos, A. P. W. ;
Hayes, B. J. ;
Spelman, R. J. ;
Goddard, M. E. .
GENETICS, 2008, 179 (03) :1503-1512