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

• Published in: Nature communications Vol. 13; no. 1; pp. 4664 - 11
• Main Authors: Huang, Qin Qin, Sallah, Neneh, Dunca, Diana, Trivedi, Bhavi, Hunt, Karen A., Hodgson, Sam, Lambert, Samuel A., Arciero, Elena, Wright, John, Griffiths, Chris, Trembath, Richard C., Hemingway, Harry, Inouye, Michael, Finer, Sarah, van Heel, David A., Lumbers, R. Thomas, Martin, Hilary C., Kuchenbaecker, Karoline
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.08.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/43; 631/114/2413; 631/208/1516; 692/699/75; Asian People - genetics; Blood pressure; Cardiovascular disease; Cardiovascular diseases; Coronary artery; Coronary artery disease; Coronary Artery Disease - epidemiology; Coronary Artery Disease - genetics; Coronary vessels; Electronic health records; Electronic medical records; Gene loci; Genetic Loci; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health risks; Heart diseases; Humanities and Social Sciences; Humans; Lipids; multidisciplinary; Pakistan; Polygenic inheritance; Polymorphism, Single Nucleotide; Populations; Reclassification; Risk analysis; Risk factors; Science; Science (multidisciplinary); Vein & artery diseases; Pakistan
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32095-5

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. Most genetic studies of disease have been done in European ancestry cohorts, and the relevance to other populations is not guaranteed. Here, the authors use data from 22,000 British South Asian individuals and find that the transferability of polygenic scores was high for lipids and blood pressure, and lower for BMI and coronary artery disease.