Allowing for population stratification in association analysis.
In genetic association studies, it is necessary to correct for population structure to avoid inference bias. During the past decade, prevailing corrections often only involved adjustments of global ancestry differences between sampled individuals. Nevertheless, population structure may vary across local genomic regions due to the variability of local ancestries associated with natural selection, migration, or random genetic drift. Adjusting for global ancestry alone may be inadequate when local population structure is an important confounding factor. In contrast, adjusting for local ancestry can more effectively prevent false-positives due to local population structure. To more accurately locate disease genes, we recommend adjusting for local ancestries by interrogating local structure. In practice, locus-specific ancestries are usually unknown and cannot be accurately inferred when ancestral population information is not available. For such scenarios, we propose employing local principal components (PC) to represent local ancestries and adjusting for local PCs when testing for genotype-phenotype association. With an acceptable computation burden, the proposed algorithm successfully eliminates the known spurious association between SNPs in the LCT gene and height due to the population structure in European Americans.
Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA. hxq21@case.edu
Huaizhen
H
Qin
Xiaofeng
X
Zhu
D056726:Genetic Association Studies; D005828:Genetics, Population; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012984:Software