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

Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals.
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DOI:
10.1038/s41467-022-32095-5
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发表时间:
2022-08-09
影响因子:
16.6
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--
中科院分区:
综合性期刊1区
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南亚血统的人比其他人群患心脏病的风险更高,但在很大程度上被排除在基因研究之外。利用来自基因与健康队列的2.2万名英国、巴基斯坦和孟加拉国个人的相关电子健康记录的数据,我们进行了冠状动脉疾病及其关键风险因素的全基因组关联研究。使用功率调整的可转移性比率,我们发现了大多数心脏代谢位点可转移性的证据。血脂和血压的多基因评分较高,但BMI和冠状动脉疾病的多基因评分较低。在临床危险因素中加入冠状动脉疾病的多基因评分,可显著改善再分类。在使用可转移基因座作为工具的孟德尔随机化中,我们的发现与欧洲血统个体的结果一致。综上所述,性状位点在种群间的特异性可转移性是一个重要的考虑因素,对风险预测和因果推理具有重要意义。大多数疾病的遗传研究都是在欧洲血统人群中进行的,与其他人群的相关性并不能得到保证。在这里,作者使用了来自22000名英国南亚人的数据,发现多基因评分的可转移性在血脂和血压方面较高,在BMI和冠状动脉疾病方面较低。
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.
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DOI: 10.1038/ng.156
发表时间: 2008-06-01
期刊: NATURE GENETICS
影响因子: 30.8
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