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Physician-confirmed and administrative definitions of stroke in UK Biobank reflect the same underlying genetic trait.

By Kristiina Rannikmae, Konrad Rawlik, Amy C. Ferguson, Nikos Avramidis, Muchen Jiang, Nicola Pirastu, Xia Shen, Emma Davidson, Rebecca Woodfield, Rainer Malik, Martin Dichgans, Albert Tenesa, Cathie Sudlow

Posted 01 Oct 2021
medRxiv DOI: 10.1101/2021.09.30.21264348

Background: Stroke in UK Biobank (UKB) is ascertained via linkages to coded administrative datasets and self-report. We studied the accuracy of these codes using genetic validation. Methods: We compiled stroke-specific and broad cerebrovascular disease (CVD) code lists (Read V2/V3, ICD-9/-10) for medical settings (hospital, death record, primary care) and self-report. Among 408,210 UKB participants we identified all with a relevant code, creating 12 stroke definitions based on the code type and source. We performed genome-wide association studies (GWASs) for each definition, comparing summary results against the largest published stroke GWAS (MEGASTROKE), assessing genetic correlations, and replicating 32 stroke-associated loci. Results: Stroke case numbers identified varied widely from 3,976 (primary care stroke-specific codes) to 19,449 (all codes, all sources). All 12 UKB stroke definitions were significantly correlated with the MEGASTROKE summary GWAS results (rg 0.81-1) and each other (rg 0.4-1). However, Bonferroni-corrected confidence intervals were wide, suggesting limited precision of some results. Six previously reported stroke-associated loci were replicated using [≥]1 UKB stroke definitions. Conclusions: Stroke case numbers in UKB depend on the code source and type used, with a 5-fold difference in the maximum case-sample size. All stroke definitions are significantly genetically correlated with the largest stroke GWAS to date.

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