Fine-scale population structure and widespread conservation of genetic effect sizes between human groups across traits

Understanding genetic differences between populations is essential for avoiding confounding in genome-wide association studies and improving polygenic score (PGS) portability. We developed a statistical pipeline to infer fine-scale Ancestry Components and applied it to UK Biobank data. Ancestry Components identify population structure not captured by widely used principal components, improving stratification correction for geographically correlated traits. To estimate the similarity of genetic effect sizes between groups, we developed ANCHOR, which estimates changes in the predictive power of an existing PGS in distinct local ancestry segments. ANCHOR infers highly similar (estimated correlation 0.98 ± 0.07)…

• W
  Wellcome

  Awards: 212284/Z/18/Z, 224575/Z/21/Z, 200186/Z/15/Z, 222334/Z/21/Z