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. 2022 Feb 2:12:787107.
doi: 10.3389/fneur.2021.787107. eCollection 2021.

Physician-Confirmed and Administrative Definitions of Stroke in UK Biobank Reflect the Same Underlying Genetic Trait

Kristiina Rannikmäe  1 , Konrad Rawlik  2 , Amy C Ferguson  1 , Nikos Avramidis  3 , Muchen Jiang  4 , Nicola Pirastu  5 , Xia Shen  5   6   7 , Emma Davidson  8 , Rebecca Woodfield  9 , Rainer Malik  10 , Martin Dichgans  10   11   12 , Albert Tenesa  1   2   13 , Cathie Sudlow  1   14
Affiliations

Physician-Confirmed and Administrative Definitions of Stroke in UK Biobank Reflect the Same Underlying Genetic Trait

Kristiina Rannikmäe et al. Front Neurol. .

Abstract

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: The 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.81-1) and each other (rg.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 definition.

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.

Keywords: accuracy; genetic correlation; routinely collected health data; stroke; validation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Genetic correlation of UKB stroke definitions with MEGASTROKE and each other. Where the rg was >1, we rounded it to 1.
Figure 2
Figure 2
Confidence intervals of genetic correlation of UKB stroke definitions with MEGASTROKE and each other. The upper triangle displays Bonferroni corrected upper confidence intervals, and the lower triangle displays Bonferroni corrected lower confidence intervals. Where the rg was >1, we rounded it to 1.
Figure 3
Figure 3
MEGASTROKE stroke subtype-significant loci replicated using UK Biobank stroke definitions. MEGASTROKE odds ratio and p-value is shown for the analyses (European or trans-ethnic) showing the lowest p-value.
See this image and copyright information in PMC

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