Extended Data Fig. 4: Association analysis of GLPR1 receptor function and random glucose effects of coding variants. | Nature Genetics

Extended Data Fig. 4: Association analysis of GLPR1 receptor function and random glucose effects of coding variants.

From: GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification

Extended Data Fig. 4

Minor allele frequency-weighted linear regression was used to test if mini-Gs response to GLP-1 stimulation significantly predicted point estimates of GLP1R variant effect on RG levels (AST20 βRG as estimated in whole-exome sequencing data from the UKBB study). Mini-Gs response to GLP-1 stimulation was corrected for variant surface expression (nmax = 22, exact n for each variant is provided in Supplementary Table 11). Error bars extend one standard error above and below the point estimate. Size of the dots is proportional to the weight applied in the regression model (Methods). The regression results (coefficient of determination R2 = 0.56, F(1, 14) = 20.1, P = 5.2 × 10−4) suggest that mini-Gs coupling in response to GLP-1 stimulation predicts the effect of these coding variants on RG levels (AST20 βRG = − 0.028; 95% CI = −0.042 to −0.015; P = 5.2 × 10−4). The gray shaded area around the regression line corresponds to the 95% confidence interval of predictions from the model. Variants in red showed no detectable surface expression (NDE) and are not included in regression analysis.

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