In a comprehensive multi-ancestry GWAS meta-analysis, researchers identified 451 risk variants for prostate cancer, including 187 new variants, demonstrating the utility of such studies across diverse populations.
By Tarun Sai LomteNov 12 2023Reviewed by Susha Cheriyedath, M.Sc. In a recent research letter published in the journal Nature Genetics, researchers performed a genome-wide association study meta-analysis of prostate cancer.
The study and findings The present study performed a GWAS meta-analysis of prostate cancer in people of multiple ancestry groups. The study included 122,188 European, 10,809 East Asian, 19,391 African, and 3,931 Hispanic prostate cancer cases. A fixed-effect meta-analysis was performed per ancestry group. In total, > 42.4 million variants with minor allele frequency > 0.1% were assessed for associations with the risk of prostate cancer.
Next, they performed a permutation test controlling for linkage disequilibrium patterns and MAF to determine the extent to which risk variants exhibited prostate-specific regulatory function. Risk variants were enriched in regions of prostate-specific regulatory activity across candidate cis-regulatory elements and splicing and expression quantitative trait loci.
That is, 69% to 70% of males in the highest or lowest quintile were in the same quintile between GRS269 and GRS451, compared to 58% between GRS100 and GRS181. In addition, the percentage of cases increased within higher categories and decreased within lower categories in each population. Risk classification with GRS and age by net re-classification index showed substantial improvement from GRS100 to GRS451.
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