Genetic architecture of routinely acquired blood tests in a British South Asian cohort
Benjamin M. Jacobs, Daniel Stow, Sam Hodgson, Julia Zöllner, Miriam Samuel, Stavroula Kanoni, Saeed Bidi, Shaheen Akhtar, Mohammad Yaser Anwar, Elena Arciero, Omar Asgar, Samina Ashraf, Saeed Bidi, Gerome Breen, James Broster, Raymond Chung, David Collier, Charles Curtis, Shabana Chaudhary, Megan Clinch, Grainne Colligan, Panos Deloukas, Ceri Durham, Faiza Durrani, Fabíola Eto, Sarah Finer, Joseph Gafton, Ana Angel Garcia, Chris Griffiths, Joanne E. Harvey, Teng Heng, Sam Hodgson, Qin Qin Huang, Matt Hurles, Karen A. Hunt, Shapna Hussain, Kamrul Islam, Vivek Iyer, Ben Jacobs, Ahsan Khan, Cath Lavery, Sang Hyuck Lee, Robin G. Lerner, Daniel G. MacArthur, Daniel Malawsky, Hilary C. Martin, Dan Mason, Rohini Mathur, Mohammed Bodrul Mazid, John McDermott, Caroline E Morton, Bill Newman, Elizabeth Owor, Asma Qureshi, Samiha Rahman, Shwetha Ramachandrappa, Mehru Reza, Jessry Russell, Nishat Safa, Miriam Samuel, Michael A. Simpson, John Solly, Marie Spreckley, Daniel Stow, Michael D. Taylor, Richard C. Trembath, Karen Tricker, Nasir Uddin, David A. van Heel, Klaudia Walter, Caroline Winckley, S. M. Wood, John Wright, Julia Zöllner, Klaudia Walter, Claudia Langenberg, Ruth Dobson, Sarah Finer, Caroline E Morton, Moneeza K. Siddiqui, Hilary C. Martin, Maik Pietzner, Rohini Mathur, David A. van Heel
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-T 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.