LAUSR

Large studies use genotype data to discover genetic contributions to complex traits and infer relationships between those traits. Co-incident geographical variation in genotypes and health traits can bias these analyses. Here we show that single genetic variants and genetic scores composed of multiple variants are associated with birth location within UK Biobank and that geographic structure in genotype data cannot be accounted for using routine adjustment for study centre and principal components derived from genotype data. We find that major health outcomes appear geographically structured and that coincident structure in health outcomes and genotype data can yield biased associations. Understanding and accounting for this phenomenon will be important when making inference from genotype data in large studies.Population structure can bias the results of genetic and epidemiological analysis. Here, Haworth et al. report that fine-scale structure is detectable in apparently homogeneous samples such as ALSPAC when measured very precisely, and remains detectable in UK Biobank despite conventional approaches to account for it.