Fig. 4: Cross-ancestry meta-analysis and fine mapping at the PIEZO1 locus for HbA1c.
From: Genetic architecture of routinely acquired blood tests in a British South Asian cohort
A Locus plot showing the regional association of at the PIEZO1 locus for HbA1c in the Genes & Health GWAS. The lead variant is coloured in purple, and other variants are coloured according to their strength of LD with the lead variant (derived from the 1000 Genomes reference samples of South Asian ancestry). B Panels display the regional association results at the PIEZO1 locus on chromosome 16 from UKB EUR-ancestry GWAS (top, N = 400,825), Genes & Health SAS GWAS (middle, N = 30,967), UKB SAS-ancestry GWAS (third from top, N = 8329) and cross-ancestry fine mapping (SuSieEx, bottom). Points are coloured according to their LD with the lead variant in each ancestry for the top three panels, which is labelled with the SNP identifier. For the bottom panel, each of the independent credible sets is coloured separately and indicated in the legend. Of the six causal signals, one was SAS-specific (indicated as ‘CS1’ on the plot), i.e. the causal signal had a posterior probability of >0.8 in the Genes & Health SAS and UKB SAS ancestries, but no other ancestry group in UKB (of EUR, AFR and EAS). This signal was mapped to a single causal variant, chr16-88716656-G-T. The top SNPs—i.e. the SNP with PIP > 0.1—are shown per credible set. Genomic co-ordinates are in hg38. C Forest plot showing pleiotropic association of the missense variant in PIEZO1 (chr16-88716656-G-T; rs563555492) with various red cell traits in Genes & Health. Beta effect sizes represent the per-allele effect on rank-inverse normalised trait values in the Genes & Health GWAS. Error bars represent the 95% confidence interval, and are centred on the effect size estimate. Associations achieving study-wide significance are coloured in, the remainder are shown as translucent. Sample sizes differ by trait and are shown in Supplementary Data 3.
