RT Journal Article
SR Electronic
T1 Testing for genetic associations in arbitrarily structured populations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 012682
DO 10.1101/012682
A1 Minsun Song
A1 Wei Hao
A1 John D. Storey
YR 2014
UL http://biorxiv.org/content/early/2014/12/12/012682.abstract
AB We present a new statistical test of association between a trait (either quantitative or binary) 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 that measured in genome-wide associations 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 environmental 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. We provide some discussion on its similarities and differences with the linear mixed model and principal component approaches.