Fig. 3: Binding- and signalling-based grouping of GIPR variants and their respective burden association on cardiometabolic phenotypes in the UK Biobank.
a, The overlap between non-synonymous GIPR variants found in the Danish population and the UK Biobank. N, total cohort sample size. b, The pharmacological profile for all GIPR variants in terms of cAMP accumulation (efficacy (Eff.) at 100 pM GIP), binding ability and β-arrestin recruitment compared with WT receptor clustered into six in vitro phenotype groups. c, A forest plot showing burden test statistics in the UK Biobank cohort (N = ~440,000). Carriers represent the number of individuals for each phenotype carrying any of the GIPR variants within that GIPR variant group. q, FDR-adjusted P values of the burden tests (performed using ACAT-O). pLoF denotes variants predicted to cause loss of function with VEP47 and/or CADD score > 30, that is, pLoF variants were not functionally characterized. aThe WT-likecAMP/WT-likearr variant, E354Q, was excluded from burden testing due to high MAF (~20%). Beta represents the effect size as standard deviation of the phenotype with error bars representing the 95% CI.
