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Apparent latent structure within the UK Biobank sample has implications for epidemiological analysis

Research output: Contribution to journalArticle

Original languageEnglish
Article number333
Number of pages9
JournalNature Communications
Issue number1
Early online date18 Jan 2019
DateAccepted/In press - 9 Nov 2018
DateE-pub ahead of print - 18 Jan 2019
DatePublished (current) - 1 Dec 2019


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.

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