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 van Heel; R Thomas Lumbers; Hilary C Martin; Karoline Kuchenbaecker
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.
Journal NATURE COMMUNICATIONS
ISSN 2041-1723
Published 09 Aug 2022
Volume 13
Issue 1
Pages 4664 4664
DOI 10.1038/s41467-022-32095-5
Type Journal Article | Research Support, Non-U.S. Gov't
Sponsorship