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• W3098256805 abstract "Abstract Background Accurate assessment of health disparities requires unbiased knowledge of genetic risks in different populations. Unfortunately, most genome-wide association studies use genotyping arrays and European samples. Here, we integrate whole genome sequence data from global populations, results from thousands of GWAS, and extensive computer simulations to identify how genetic disease risks can be misestimated. Results In contrast to null expectations, we find that risk allele frequencies at known disease loci are significantly different for African populations compared to other continents. Strikingly, ancestral risk alleles are found at 9.51% higher frequency in Africa and derived risk alleles are found at 5.40% lower frequency in Africa. By simulating GWAS with different study populations, we find that non-African cohorts yield disease associations that have biased allele frequencies and that African cohorts yield disease associations that are relatively free of bias. We also find empirical evidence that genotyping arrays and SNP ascertainment bias contribute to continental differences in risk allele frequencies. Because of these causes, polygenic risk scores can be grossly misestimated for individuals of African descent. Importantly, continental differences in risk allele frequencies are only moderately reduced if GWAS use whole genome sequences and hundreds of thousands of cases and controls. Finally, comparisons between uncorrected and corrected genetic risk scores reveal the benefits of considering whether risk alleles are ancestral or derived. Conclusions Our results imply that caution must be taken when extrapolating GWAS results from one population to predict disease risks in another population." @default.
• W3098256805 created "2020-11-23" @default.
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• W3098256805 date "2017-09-28" @default.
• W3098256805 modified "2023-09-28" @default.
• W3098256805 title "How genetic disease risks can be misestimated across global populations" @default.
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• W3098256805 doi "https://doi.org/10.1101/195768" @default.
• W3098256805 hasPublicationYear "2017" @default.
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