Genetic architecture of routinely acquired blood tests in a British South Asian cohort

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Genetic architecture of routinely acquired blood tests in a British South Asian cohort

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 im portance of ancestral diversity in genetic studies. © The Author(s) 2024.

Authors : Jacobs B.M.; Stow D.; Hodgson S.; Zöllner J.; Samuel M.; Kanoni S.; Bidi S.; Wright J.; Wood S.; Winckley C.; Walter K.; van Heel D.A.; Uddin N.; Tricker K.; Trembath R.C.; Taylor M.; Spreckley M.; Solly J.; Simpson M.; Safa N.; Russell J.; Reza M.; Ramachandrappa S.; Rahman S.; Qureshi A.; Owor E.; Newman B.; Morton C.; McDermott J.; Mazid M.B.; Mathur R.; Mason D.; Martin H.C.; Malawsky D.; MacArthur D.; Lerner R.; Lee S.H.; Lavery C.; Khan A.; Iyer V.; Islam K.; Hussain S.; Hunt K.A.; Hurles M.; Huang Q.Q.; Heng T.; Harvey J.; Griffiths C.; Garcia A.A.; Gafton J.; Finer S.; Eto F.; Durrani F.; Durham C.; Deloukas P.; Colligan G.; Clinch M.; Chaudhary S.; Curtis C.J.; Collier D.; Chung R.; Broster J.; Breen G.; Ashraf S.; Asgar O.; Arciero E.; Anwar M.; Akhtar S.; Langenberg C.; Dobson R.; Siddiqui M.K.; Pietzner M.

Source : Nature Research