2021
DOI: 10.1101/2021.06.22.21259323
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Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistanis and Bangladeshis

Abstract: Background: Individuals with South Asian ancestry have higher risk of heart disease than other groups in Western countries; however, most genetic research has focused on European-ancestry (EUR) individuals. It is unknown whether reported genetic loci and polygenic scores (PGSs) for cardiometabolic traits are transferable to South Asians, and whether PGSs have utility in clinical settings. Methods: Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from th… Show more

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Cited by 12 publications
(14 citation statements)
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“…This suggested that a large proportion (75%) of the loci ascertained in EUR populations, which were well powered to replicate in G&H did so. We did not observe any loci that were well powered (power to replicate >0.8) but not transferable in G&H. The evidence of transferability was consistent with other cardiometabolic traits (Observed/Expected = 0.62 for coronary artery disease and 1.0 to 1.2 for BMI, lipids, and blood pressure) that were reported in the same cohort [ 9 ].…”
Section: Resultssupporting
confidence: 82%
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“…This suggested that a large proportion (75%) of the loci ascertained in EUR populations, which were well powered to replicate in G&H did so. We did not observe any loci that were well powered (power to replicate >0.8) but not transferable in G&H. The evidence of transferability was consistent with other cardiometabolic traits (Observed/Expected = 0.62 for coronary artery disease and 1.0 to 1.2 for BMI, lipids, and blood pressure) that were reported in the same cohort [ 9 ].…”
Section: Resultssupporting
confidence: 82%
“…For example, we observed shared causal variants at the TCF7L2 locus, one of the known loci with the strongest association with T2D, and at the KCNJ11 locus, which is the target gene for drugs such as Glyburide [ 41 , 42 ]. The proportion of transferable loci with shared causal variants for T2D was lower than for triglycerides (56%; binomial p -value = 0.015) and total cholesterol (61%; p = 0.003) and similar to HDL (48%), LDL (47%), and BMI (26%) (binomial p -value >0.05 for all) in the same cohort [ 9 ].…”
Section: Resultsmentioning
confidence: 99%
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“…Differences in allele frequencies, linkage disequilibrium between ancestry groups, and variable sample sizes impacted our power to observe associations for each group. We recently developed power-adjusted transferability ratios, an approach to account for all these factors by comparing observed transferable loci to what is expected for a study of a given ancestry and sample size 28 . The PAT ratios were about 30% for African, South Asian, and East Asian ancestry, remarkably similar and consistently low.…”
Section: Discussion 13mentioning
confidence: 99%