Physician-Confirmed and Administrative Definitions of Stroke in UK Biobank Reflect the Same Underlying Genetic Trait.
accuracy
genetic correlation
routinely collected health data
stroke
validation
Journal
Frontiers in neurology
ISSN: 1664-2295
Titre abrégé: Front Neurol
Pays: Switzerland
ID NLM: 101546899
Informations de publication
Date de publication:
2021
2021
Historique:
received:
01
10
2021
accepted:
13
12
2021
entrez:
21
2
2022
pubmed:
22
2
2022
medline:
22
2
2022
Statut:
epublish
Résumé
Stroke in UK Biobank (UKB) is ascertained 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. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
Stroke in UK Biobank (UKB) is ascertained
METHODS
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
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
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.
Identifiants
pubmed: 35185750
doi: 10.3389/fneur.2021.787107
pmc: PMC8847736
doi:
Types de publication
Journal Article
Langues
eng
Pagination
787107Informations de copyright
Copyright © 2022 Rannikmäe, Rawlik, Ferguson, Avramidis, Jiang, Pirastu, Shen, Davidson, Woodfield, Malik, Dichgans, Tenesa and Sudlow.
Déclaration de conflit d'intérêts
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.
Références
PLoS One. 2015 Oct 23;10(10):e0140533
pubmed: 26496350
Nat Genet. 2015 Mar;47(3):284-90
pubmed: 25642633
Neurology. 2020 Aug 11;95(6):e697-e707
pubmed: 32616677
Nat Genet. 2018 May;50(5):668-681
pubmed: 29700475
PLoS One. 2015 Aug 20;10(8):e0135834
pubmed: 26292280
Nat Genet. 2020 Apr;52(4):458-462
pubmed: 32203469
Circulation. 2020 Mar 3;141(9):e139-e596
pubmed: 31992061
Neurologist. 2018 Jul;23(4):118-121
pubmed: 29953034
Am J Hum Genet. 2020 May 7;106(5):611-622
pubmed: 32275883
Nat Genet. 2020 Aug;52(8):859-864
pubmed: 32601477
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Nat Genet. 2018 Apr;50(4):524-537
pubmed: 29531354
Nat Protoc. 2014 May;9(5):1192-212
pubmed: 24762786
Am J Hum Genet. 2011 Mar 11;88(3):294-305
pubmed: 21376301
Genetics. 2018 Apr;208(4):1397-1408
pubmed: 29429966
Lancet Digit Health. 2020 Nov;2(11):e567-e568
pubmed: 33103095
Lancet. 2012 Dec 15;380(9859):2095-128
pubmed: 23245604
Am J Epidemiol. 2017 Nov 1;186(9):1026-1034
pubmed: 28641372
Nat Neurosci. 2019 Mar;22(3):343-352
pubmed: 30718901