Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Clin Genet. 2019 Jul;96(1):17-27. doi: 10.1111/cge.13527. Epub 2019 Apr 1.
Remarkable findings from genome-wide association studies (GWAS) on blood pressure (BP) traits have made new insights for developing precision medicine toward more effective screening measures. However, generality of GWAS findings in diverse populations is hampered by some technical limitations. There is no comprehensive study to evaluate source(s) of the non-generality of GWAS results on BP traits, so to fill the gap, this systematic review study was carried out. Using MeSH terms, 1545 records were detected through searching in five databases and 49 relevant full-text articles were included in our review. Overall, 749 unique variants were reported, of those, majority of variants have been detected in Europeans and were associated to systolic and diastolic BP traits. Frequency of genetic variants with same position was low in European and non-European populations (n = 38). However, more than 200 (>25%) single nucleotide polymorphisms were found on same loci or linkage disequilibrium blocks (r ≥ 80%). Investigating for locus position and linkage disequilibrium of infrequent unique variants showed modest to high reproducibility of findings in Europeans that in some extent was generalizable in other populations. Beyond theoretical limitations, our study addressed other possible sources of non-generality of GWAS findings for BP traits in the same and different origins.
全基因组关联研究（GWAS）在血压（BP）特征方面的显著发现为开发针对更有效筛选措施的精准医学提供了新的见解。然而，GWAS 发现的普遍性在不同人群中受到一些技术限制的阻碍。目前还没有全面的研究来评估 BP 特征 GWAS 结果非普遍性的来源，因此为了填补这一空白，进行了这项系统评价研究。使用 MeSH 术语，通过在五个数据库中搜索，共检测到 1545 条记录，并纳入了 49 篇相关的全文文章。总体而言，报告了 749 个独特的变异体，其中大多数变异体已在欧洲人群中检测到，并与收缩压和舒张压特征相关。在欧洲和非欧洲人群中，具有相同位置的遗传变异体的频率较低（n=38）。然而，在相同的基因座或连锁不平衡块（r≥80%）上发现了超过 200 个（>25%）单核苷酸多态性。对罕见独特变异体的基因座位置和连锁不平衡的研究表明，在欧洲人群中，这些发现具有中等至高度的可重复性，在一定程度上可以推广到其他人群。除了理论上的限制，我们的研究还解决了 BP 特征 GWAS 结果在相同和不同来源的非普遍性的其他可能来源。
