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-T<sub>T</sub> - 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.
Authors
- Daniel G. MacArthur (ORCID: https://orcid.org/0000-0002-5771-2290)
- Chris Griffiths (ORCID: https://orcid.org/0000-0001-7935-8694)
- Daniel Shiloh Malawsky (ORCID: https://orcid.org/0000-0003-4421-8688)
- Gerome D. Breen (ORCID: https://orcid.org/0000-0003-2053-1792)
- Maik Pietzner (ORCID: https://orcid.org/0000-0003-3437-9963)
- David Collier (ORCID: https://orcid.org/0000-0003-4087-1559)
- Klaudia Walter (ORCID: https://orcid.org/0000-0003-4448-0301)
- Shwetha Ramachandrappa (ORCID: https://orcid.org/0000-0003-2639-766X)
- Stavroula Kanoni (ORCID: https://orcid.org/0000-0002-1691-9615)
- Rohini Mathur (ORCID: https://orcid.org/0000-0002-3817-8790)
- John McDermott (ORCID: https://orcid.org/0000-0002-5220-8837)
- Benjamin M. Jacobs (ORCID: https://orcid.org/0000-0002-6023-6010)
- Mohammed Bodrul Mazid
- Ruth Dobson (ORCID: https://orcid.org/0000-0002-2993-585X)
- David A. van Heel (ORCID: https://orcid.org/0000-0002-0637-2265)
- Elena Arciero (ORCID: https://orcid.org/0000-0002-5709-607X)
- Julia Zöllner (ORCID: https://orcid.org/0000-0002-9072-9131)
- Robin G. Lerner (ORCID: https://orcid.org/0000-0002-8372-8181)
- Teng Heng
- Kamrul Islam (ORCID: https://orcid.org/0000-0002-5968-7068)
- Caroline Winckley
- Megan Clinch (ORCID: https://orcid.org/0000-0003-0375-8629)
- Michael A. Simpson (ORCID: https://orcid.org/0000-0002-8539-8753)
- Richard C. Trembath (ORCID: https://orcid.org/0000-0003-0550-3400)
- Dan Mason (ORCID: https://orcid.org/0000-0002-0026-9216)
- Sam Hodgson (ORCID: https://orcid.org/0000-0002-5610-850X)
- Caroline E Morton (ORCID: https://orcid.org/0000-0003-0783-0042)
- Faiza Durrani (ORCID: https://orcid.org/0000-0001-8607-7049)
- Cath Lavery
- Charles Curtis (ORCID: https://orcid.org/0000-0002-2992-1941)
- Shapna Hussain
- Miriam Samuel (ORCID: https://orcid.org/0000-0003-1258-435X)
- Saeed Bidi (ORCID: https://orcid.org/0000-0002-8951-2867)
- Omar Asgar
- John Solly
- Fabíola Eto (ORCID: https://orcid.org/0000-0002-0203-8649)
- Claudia Langenberg (ORCID: https://orcid.org/0000-0002-5017-7344)
- S. M. Wood
- Qin Qin Huang (ORCID: https://orcid.org/0000-0003-3073-717X)
- Elizabeth Owor
- Samiha Rahman (ORCID: https://orcid.org/0000-0003-0677-1765)
- Marie Spreckley (ORCID: https://orcid.org/0000-0002-8346-2408)
- Mohammad Yaser Anwar (ORCID: https://orcid.org/0000-0002-2349-8214)
- Sarah Finer (ORCID: https://orcid.org/0000-0002-2684-4653)
- Asma Qureshi (ORCID: https://orcid.org/0000-0001-7857-8935)
- Moneeza K. Siddiqui (ORCID: https://orcid.org/0000-0001-9055-3896)
- Daniel Stow (ORCID: https://orcid.org/0000-0002-9534-4521)
- Hilary C. Martin (ORCID: https://orcid.org/0000-0002-4454-9084)
- Joanne E. Harvey (ORCID: https://orcid.org/0000-0001-5687-2586)
- William G. Newman (ORCID: https://orcid.org/0000-0002-6382-4678)
- Shabana Chaudhary
- Matt Hurles
- Ceri Durham
- Nishat Safa
- Grainne Colligan (ORCID: https://orcid.org/0000-0001-7357-2390)
- Panos Deloukas (ORCID: https://orcid.org/0000-0001-9251-070X)
- Joseph Gafton
- Sang Hyuck Lee (ORCID: https://orcid.org/0000-0002-5610-033X)
- James Broster
- Michael D. Taylor (ORCID: https://orcid.org/0000-0001-7009-3466)
- Ahsan Khan (ORCID: https://orcid.org/0000-0002-5189-6906)
- Shaheen Akhtar
- Raymond Chung (ORCID: https://orcid.org/0000-0003-0296-5546)
- Samina Ashraf (ORCID: https://orcid.org/0000-0002-3198-7245)
- Vivek Iyer (ORCID: https://orcid.org/0000-0003-4451-8293)
- John Wright
- Jessry Russell
- Nasir Uddin
- Karen Tricker
- Karen A. Hunt (ORCID: https://orcid.org/0000-0002-2164-6412)
- Mehru Reza
- Ana Angel Garcia
- Ben Jacobs (ORCID: https://orcid.org/0000-0003-4300-6157)
Institutions
- Garvan Institute of Medical Research (AU)
- University of Bradford (GB)
- Queen Mary University of London (GB)
- King's College London (GB)
- Barts Health NHS Trust (GB)
- Royal London Hospital (GB)
- Action for ME (GB)
- Wellcome Sanger Institute (GB)
- University of Manchester (GB)
- Manchester University NHS Foundation Trust (GB)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- William Harvey Research Institute (GB)
- NIHR Research Delivery Network (GB)
- Bradford Teaching Hospitals NHS Foundation Trust (GB)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1038/s41467-024-53091-x
- Citations
- 18
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 9.91
Funders
- Bristol-Myers Squibb
- Pfizer
- GlaxoSmithKline
- Alnylam Pharmaceuticals
- Aims2Cure
- Wellcome Trust
- Broad Institute
- Barts Charity
- Maze Therapeutics
- National Institute for Health and Care Research
- Multiple Sclerosis Society
- King's College London
- Public Health England
- Novo Nordisk
- Barts Health NHS Trust
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Economic and Social Research Council