1. Genetic architecture of routinely acquired blood tests in a British South Asian cohort
- Author
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Benjamin M. Jacobs, Daniel Stow, Sam Hodgson, Julia Zöllner, Miriam Samuel, Stavroula Kanoni, Saeed Bidi, Genes & Health Research Team, Klaudia Walter, Claudia Langenberg, Ruth Dobson, Sarah Finer, Caroline Morton, Moneeza K. Siddiqui, Hilary C. Martin, Maik Pietzner, Rohini Mathur, and David A. van Heel
- Subjects
Science - Abstract
Abstract 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-TT - 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.
- Published
- 2024
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