Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
Department of Neurology, Royal London Hospital, Barts Health NHS Trust, London, UK.
Nat Commun. 2024 Oct 16;15(1):8929. doi: 10.1038/s41467-024-53091-x.
Understanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Healthcare Records (EHRs) of ~50,000 British Bangladeshi and British Pakistani adults. We demonstrate a causal variant within the PIEZO1 locus which was associated with alterations in red cell traits and glycated haemoglobin. Conditional analysis and within-ancestry fine mapping confirmed that this signal is driven by a missense variant - chr16-88716656-G-T - which is common in South Asian ancestries (MAF 3.9%) but ultra-rare in other ancestries. Carriers of the T allele had lower mean HbA1c values, lower HbA1c values for a given level of random or fasting glucose, and delayed diagnosis of Type 2 Diabetes Mellitus. Our results shed light on the genetic basis of clinically-relevant traits in an under-represented population, and emphasise the importance of ancestral diversity in genetic studies.
了解常规获得的血液检测的遗传基础可以深入了解人类生理学的几个方面。我们报告了一项针对 5 万名英国孟加拉裔和英国巴基斯坦裔成年人的电子健康记录 (EHR) 中定义的 42 种定量血液检测特征的全基因组关联研究。我们在 PIEZO1 基因座内发现了一个与红细胞特征和糖化血红蛋白改变相关的因果变异。条件分析和同系精细映射证实，该信号由一个错义变异驱动 - chr16-88716656-G-T - 该变异在南亚血统中很常见（MAF 为 3.9%），但在其他血统中极为罕见。携带 T 等位基因的个体的平均 HbA1c 值较低，给定随机或空腹血糖水平下的 HbA1c 值较低，并且 2 型糖尿病的诊断延迟。我们的研究结果揭示了遗传基础在代表性不足的人群中的临床相关特征，并强调了遗传研究中祖先多样性的重要性。
