title: A Generalized Sequential Bonferroni Procedure for GWAS in Admixed Populations Incorporating Admixture Mapping Information into Association Tests.
abstract: OBJECTIVE
  To develop effective methods for GWAS in admixed populations such as African Americans.
  
  
  METHODS
  We show that, when testing the null hypothesis that the test SNP is not in background linkage disequilibrium with the causal variants, several existing methods cannot control well the family-wise error rate (FWER) in the strong sense in GWAS. These existing methods include association tests adjusting for global ancestry and joint association tests that combine statistics from admixture mapping tests and association tests that correct for local ancestry. Furthermore, we describe a generalized sequential Bonferroni (smooth-GSB) procedure for GWAS that incorporates smoothed weights calculated from admixture mapping tests into association tests that correct for local ancestry. We have applied the smooth-GSB procedure to analyses of GWAS data on American Africans from the Atherosclerosis Risk in Communities (ARIC) Study.
  
  
  RESULTS
  Our simulation studies indicate that the smooth-GSB procedure not only control the FWER, but also improves statistical power compared with association tests correcting for local ancestry.
  
  
  CONCLUSIONS
  The smooth-GSB procedure can result in a better performance than several existing methods for GWAS in admixed populations.
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University, Richmond, Va., USA.
authors.forename: Wenan
authors.initials: W
authors.lastname: Chen
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Ren
authors.forename: Huaizhen
authors.initials: H
authors.lastname: Qin
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Archer
authors.forename: Weiwei
authors.initials: W
authors.lastname: Ouyang
authors.forename: Nianjun
authors.initials: N
authors.lastname: Liu
authors.forename: Xiangning
authors.initials: X
authors.lastname: Chen
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Shumei
authors.initials: S
authors.lastname: Sun
authors.forename: Guimin
authors.initials: G
authors.lastname: Gao
mesh_terms: D001741:Black or African American / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics; D002874:Chromosome Mapping; D003198:Computer Simulation; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide