Microarray genotyping resource to determine population stratification in genetic associationstudies of complex disease

摘要

We have developed a robust mic roar ray genotyping chip that will help advance studies in genetic, epidemiology. In population-based genetic association studies of complex disease there could be hidden genetic substructure in the study populations, resulting in false-positive associations Such population stratification may confound efforts to identify true associations between genotype/hap-lotype and phenotype Methods relying on genotyping additional null single nudeolide polymorphism (SNP) markers have been proposed suchas genomic control (GC) and structured association (SA), to correct association tests for population stratification If there is an association of a disease with null SNPs, this suggests that there is a population subset with different genetic background plus different disease susceptibility Genotyping over 100 null SNPs in the large numbets of patient and control DNA samples that are required in genetic association studies can be prohibitively expensive We have therefore developedand tested a re sequencing chip based on arrayed primer extension (APEX) from, over 2000 DNA probe features that facilitate multiple interrogations of each SNP, providing a powerful, accurate, and economical means to simultaneously determine the genotypes at 110 null SNP loci in any individual. Based on 1141 known genotypes from other research groups, our GC SNP chip has an accuracy of 98 5%, including non-calls.