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Polygenic risk for coronary artery disease in the Scottish and English population.
BMC Cardiovasc. Disord. 21:586 (2021)
BACKGROUND: Epidemiological studies have repeatedly observed a markedly higher risk for coronary artery disease (CAD) in Scotland as compared to England. Up to now, it is unclear whether environmental or genetic factors might explain this phenomenon. METHODS: Using UK Biobank (UKB) data, we assessed CAD risk, based on the Framingham risk score (FRS) and common genetic variants, to explore the respective contribution to CAD prevalence in Scotland (n = 31,963) and England (n = 317,889). We calculated FRS based on sex, age, body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), antihypertensive medication, smoking status, and diabetes. We determined the allele frequency of published genome-wide significant risk CAD alleles and a weighted genetic risk score (wGRS) for quantifying genetic CAD risk. RESULTS: Prevalence of CAD was 16% higher in Scotland as compared to England (8.98% vs. 7.68%, P < 0.001). However, the FRS only predicted a marginally higher CAD risk (less than 1%) in Scotland (12.5 ± 10.5 vs.12.6 ± 10.6, P = 0.03). Likewise, the overall number of genome-wide significant variants affecting CAD risk (157.6 ± 7.7 and 157.5 ± 7.7; P = 0.12) and a wGRS for CAD (2.49 ± 0.25 in both populations, P = 0.14) were remarkably similar in the English and Scottish population. Interestingly, we observed substantial differences in the allele frequencies of individual risk variants. Of the previously described 163 genome-wide significant variants studied here, 35 variants had higher frequencies in Scotland, whereas 37 had higher frequencies in England (P < 0.001 each). CONCLUSIONS: Neither the traditional risk factors included in the FRS nor a genetic risk score (GRS) based on established common risk alleles explained the higher CAD prevalence in Scotland. However, we observed marked differences in the distribution of individual risk alleles, which emphasizes that even geographically and ethnically closely related populations may display relevant differences in the genetic architecture of a common disease.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Coronary Artery Disease ; Genetic Risk Score ; Prevalence ; Uk Biobank; Genetic Risk; Deprivation; Mortality; Prevalence; Accuracy; Therapy; England; Common
e-ISSN
1471-2261
Journal
BMC Cardiovascular Disorders
Quellenangaben
Volume: 21,
Issue: 1,
Article Number: 586
Publisher
BioMed Central
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)
Grants
German Federal Ministry of Education and Research (BMBF)
British Heart Foundation (BHF)/German Centre of Cardiovascular Research (DZHK)-collaboration
Leducq Foundation for Cardiovascular Research
German Research Foundation (DFG)
Bavarian State Ministry of Health and Care
German Federal Ministry of Economics and Energy
Federal Ministry of Education and Research
Projekt DEAL
British Heart Foundation (BHF)/German Centre of Cardiovascular Research (DZHK)-collaboration
Leducq Foundation for Cardiovascular Research
German Research Foundation (DFG)
Bavarian State Ministry of Health and Care
German Federal Ministry of Economics and Energy
Federal Ministry of Education and Research
Projekt DEAL