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African populations are vastly underrepresented in genetic studies despite having the most genetic variation globally and facing wide-ranging environmental exposures. Most of these studies have been conducted in populations of European (EUR) ancestry using GWAS arrays that represent the genetic variation in these populations. Thus, the prediction accuracy of polygenic risk scores (PRS) derived from EUR ancestry populations is less accurate in populations of non-European ancestry, and least accurate in African (AFR) ancestry populations. The extent to which PRS prediction accuracy varies within AFR ancestry populations has not, however, been previously investigated. This study had two aims: the first was to investigate the contribution of common variants to the risk of schizophrenia in the South African Xhosa (SAX) population through genome-wide association study (GWAS) analysis, and to determine if PRS derived from EUR and East Asian (EAS) ancestry populations from the Psychiatric Genomics Consortium (PGC) Schizophrenia Working Group were generalizable to SAX. The second aim was to assess the generalizability of PRS for non-psychiatric phenotypes that were derived from EUR ancestry individuals from the UK Biobank (UKB, n=~ 350,000) in the Uganda General Population Cohort (GPC, n= 4,778) and the South African Drakenstein Child Health Study (DHCS, n= 638). To address the first aim, a GWAS was conducted in 2,086 Xhosa individuals from South Africa with and without schizophrenia (ncases= 1,038; ncontrols= 1,048) using a custom-designed Affymetrix GWAS array designed to capture variation in the Xhosa …