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

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


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.



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

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Nat Commun

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Springer Science and Business Media LLC
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)