Characterizing the polygenic architecture of complex traits in populations of East Asian and European descent

To investigate the polygenicity of complex traits in populations of East Asian (EAS) and European (EUR) descents, we leveraged genome-wide data from Biobank Japan, UK Biobank, and FinnGen cohorts. Specifically, we analyzed up to 215 outcomes related to 18 health domains, assessing their polygenic architecture via descriptive statistics, such as the proportion of susceptibility SNPs per trait (π(c)). While we did not observe EAS–EUR differences in the overall distribution of polygenicity parameters across the phenotypes investigated, there were ancestry-specific patterns in the polygenicity differences between health domains. In EAS, pairwise comparisons across health domains showed enrichment for π(c) differences related to hematological and metabolic traits (hematological fold-enrichment = 4.45, p = 2.15 × 10(–7); metabolic fold-enrichment = 4.05, p = 4.01 × 10(–6)). For both categories, the proportion of susceptibility SNPs was lower than that observed for several other health domains (EAS-hematological median π(c) = 0.15%, EAS-metabolic median π(c) = 0.18%) with the strongest π(c) difference with respect to respiratory traits (EAS-respiratory median π(c) = 0.50%; hematological-p = 2.26 × 10(–3); metabolic-p = 3.48 × 10(–3)). In EUR, pairwise comparisons showed multiple π(c) differences related to the endocrine category (fold-enrichment = 5.83, p = 4.76 × 10(–6)), where these traits showed a low proportion of susceptibility SNPs (EUR-endocrine median π(c) = 0.01%) with the strongest difference with respect to psychiatric phenotypes (EUR-psychiatric median π(c) = 0.50%; p = 1.19 × 10(–4)). Simulating sample sizes of 1,000,000 and 5,000,000 individuals, we also showed that ancestry-specific polygenicity patterns translate into differences across health domains in the genetic variance explained by susceptibility SNPs projected to be genome-wide significant (e.g., EAS hematological-neoplasm p = 2.18 × 10(–4); EUR endocrine-gastrointestinal p = 6.80 × 10(–4)). These findings highlight that traits related to the same health domains may present ancestry-specific variability in their polygenicity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40246-023-00514-3.