title: An efficient empirical Bayes method for genomewide association studies.
abstract: Linear mixed model (LMM) is one of the most popular methods for genomewide association studies (GWAS). Numerous forms of LMM have been developed; however, there are two major issues in GWAS that have not been fully addressed before. The two issues are (i) the genomic background noise and (ii) low statistical power after Bonferroni correction. We proposed an empirical Bayes (EB) method by assigning each marker effect a normal prior distribution, resulting in shrinkage estimates of marker effects. We found that such a shrinkage approach can selectively shrink marker effects and reduce the noise level to zero for majority of non-associated markers. In the meantime, the EB method allows us to use an 'effective number of tests' to perform Bonferroni correction for multiple tests. Simulation studies for both human and pig data showed that EB method can significantly increase statistical power compared with the widely used exact GWAS methods, such as GEMMA and FaST-LMM-Select. Real data analyses in human breast cancer identified improved detection signals for markers previously known to be associated with breast cancer. We therefore believe that EB method is a valuable tool for identifying the genetic basis of complex traits.
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.|Department of Botany and Plant Sciences, University of California, Riverside, CA, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Botany and Plant Sciences, University of California, Riverside, CA, USA.|College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Botany and Plant Sciences, University of California, Riverside, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Xu
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000235:genetics*; D003198:Computer Simulation; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D034421:Sus scrofa / Q000235:genetics*
keywords: Effective number of tests; empirical Bayes; genomewide association studies; linear mixed model