Genetic architecture of routinely acquired blood tests in a British South Asian cohort.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39414775.
- Also identified by DOI 10.1038/s41467-024-53091-x and PMC identifier 11484750.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<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.
Medical subject headings
- Genome-Wide Association Study
- Glycated Hemoglobin
- Diabetes Mellitus, Type 2
- Asian People
- Ion Channels