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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.
Studying the genetic basis of complex traits and diseases across ancestries has the potential to improve fine-mapping resolution, uncover novel biology, and ensure that downstream
applications, such as polygenic risk score profiling, perform equitably across populations1,2,3,4,5,6. Although there is increasing ancestral diversity in published genome-wide association
studies (GWAS)7,8, our understanding of the genetic basis of complex traits and diseases remains skewed towards populations of European ancestral backgrounds9. Participants of South Asian
ancestry, despite representing ~25% of the world’s population, make up only 2% of published GWAS, even in relatively diverse cohorts such as UK Biobank (UKB) (~2%) and the Million Veterans
Programme ( 0.01, INFO > 0.7) with 42 routinely acquired quantitative blood tests derived from Electronic Healthcare Records (EHR) in the Genes and Health cohort—a genotype-phenotype cohort
comprising ~50,000 British individuals of South Asian ancestry (Supplementary Data 1 and 2). The number of participants included in the GWAS varied by phenotype, ranging from 13,870 (AST:
aspartate aminotransferase) to 38,224 (Haemoglobin, Supplementary Data 3, Fig. 1A). Across all 42 traits we found 517 study-wide significant independent locus-trait associations in the Genes
and Health cohort (Fig. 1A, P