Testing for genetic associations in arbitrarily structured populations.

TitleTesting for genetic associations in arbitrarily structured populations.
Publication TypeJournal Article
Year of Publication2015
AuthorsSong, M, Hao, W, Storey, JD
JournalNat Genet
Volume47
Issue5
Pagination550-4
Date Published2015 May
ISSN1546-1718
KeywordsComputer Simulation, Genome-Wide Association Study, Humans, Linear Models, Models, Genetic, Polymorphism, Single Nucleotide, Principal Component Analysis
Abstract

<p>We present a new statistical test of association between a trait and genetic markers, which we theoretically and practically prove to be robust to arbitrarily complex population structure. The statistical test involves a set of parameters that can be directly estimated from large-scale genotyping data, such as those measured in genome-wide association studies (GWAS). We also derive a new set of methodologies, called a 'genotype-conditional association test' (GCAT), shown to provide accurate association tests in populations with complex structures, manifested in both the genetic and non-genetic contributions to the trait. We demonstrate the proposed method on a large simulation study and on the Northern Finland Birth Cohort study. In the Finland study, we identify several new significant loci that other methods do not detect. Our proposed framework provides a substantially different approach to the problem from existing methods, such as the linear mixed-model and principal-component approaches. </p>

DOI10.1038/ng.3244
Alternate JournalNat. Genet.
PubMed ID25822090
PubMed Central IDPMC4464830
Grant ListR01 HG006448 / HG / NHGRI NIH HHS / United States