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

Qin Qin Huang, Neneh Sallah, Diana Dunca, Bhavi Trivedi, Karen A. Hunt, Sam Hodgson, Samuel A. Lambert, Elena Arciero, John Wright, Chris Griffiths, Richard C. Trembath, Harry Hemingway, Michael Inouye, Sarah Finer, David A. Heel, R. Thomas Lumbers, Hilary C. Martin and Karoline Kuchenbaecker ()
Additional contact information
Qin Qin Huang: Wellcome Sanger Institute
Neneh Sallah: University College London
Diana Dunca: University College London
Bhavi Trivedi: Queen Mary University of London
Karen A. Hunt: Queen Mary University of London
Sam Hodgson: University of Southampton
Samuel A. Lambert: University of Cambridge
Elena Arciero: Wellcome Sanger Institute
John Wright: Bradford Teaching Hospitals National Health Service (NHS) Foundation Trust
Chris Griffiths: Queen Mary University of London
Richard C. Trembath: King’s College London
Harry Hemingway: University College London
Michael Inouye: University of Cambridge
Sarah Finer: Queen Mary University of London
David A. Heel: Queen Mary University of London
R. Thomas Lumbers: University College London
Hilary C. Martin: Wellcome Sanger Institute
Karoline Kuchenbaecker: University College London

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32095-5

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