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Background  As Genome-Wide Association Studies (GWAS) have been increasingly used with data from various populations, it has been observed that data from different populations reveal different sets of Single Nucleotide Polymorphisms (SNPs) that are associated with the same disease. Using Type II Diabetes (T2D) as a test case, we develop measures and methods to characterize the functional overlap of SNPs associated with the same disease across populations.    Results  We introduce the notion of an Overlap Matrix as a general means of characterizing the functional overlap between different SNP sets at different genomic and functional granularities. Using SNP-to-gene mapping, functional annotation databases, and functional association networks, we assess the degree of functional overlap across nine populations from Asian and European ethnic origins. We further assess the generalizability of the method by applying it to a dataset for another complex disease – Prostate Cancer. Our results show that more overlap is captured as more functional data is incorporated as we go through the pipeline, starting from SNPs and ending at network overlap analyses. We hypothesize that these observed differences in the functional mechanisms of T2D across populations can also explain the common use of different prescription drugs in different populations. We show that this hypothesis is concordant with the literature on the functional mechanisms of prescription drugs.    Conclusion  Our results show that although the etiology of a complex disease can be associated with distinct processes that are affected in different populations, network-based annotations can capture more functional overlap across populations. These results support the notion that it can be useful to take ethnicity into account in making personalized treatment decisions for complex diseases.

Cross-population analysis for functional characterization of type II diabetes variants