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Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals.

Published version
Peer-reviewed

Type

Article

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Authors

Sallah, Neneh 
Dunca, Diana 
Trivedi, Bhavi 
Hunt, Karen A 

Abstract

Individuals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate. The performance of polygenic scores was high for lipids and blood pressure, but lower for BMI and coronary artery disease. Adding a polygenic score for coronary artery disease to clinical risk factors showed significant improvement in reclassification. In Mendelian randomisation using transferable loci as instruments, our findings were consistent with results in European-ancestry individuals. Taken together, trait-specific transferability of trait loci between populations is an important consideration with implications for risk prediction and causal inference.

Description

Keywords

Asian People, Coronary Artery Disease, Genetic Loci, Genome-Wide Association Study, Humans, Pakistan, Polymorphism, Single Nucleotide

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Springer Science and Business Media LLC
Sponsorship
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (RG/18/13/33946)
ESRC (ES/T013192/1)
National Institute for Health and Care Research (IS-BRC-1215-20014)