Extended Data Fig. 5: Forest plots of burden tests of cardiometabolic phenotypes in the Danish population (Inter99).
Association results of metabolic-associated biochemistry measures, estimates of beta cell function and insulin sensitivity, and cardiovascular-associated phenotypes (the lipid profile) for all variant groups are shown. Synonym, WT/WT, LoF/WT, LoF/LoF, and pLoF represent the groups of synonymous, WT-likecAMP/WT-likearr, LoFcAMP/WT-likearr, LoFcAMP/LoFarr, and predicted LoF variants, respectively. The E354Q variant was excluded from burden testing of the WT-likecAMP/WT-likearr group due to high minor allele frequency (MAF; ~20%). Abbreviations: FPG, fasting plasma glucose levels; PG, plasma glucose levels; FSI, fasting serum insulin levels; SI, serum insulin levels; FS C-pep, fasting serum C-peptide levels; HbA1c, hemoglobin A1c; AUC30ig, area under curve 0–30 min insulin/glucose; BIGTT-AIR, beta cell function insulin sensitivity glucose tolerance test (BIGTT)-acute insulin response (insulin secretion); BIGTT-SI, BIGTT-sensitivity index (insulin sensitivity); Insu index, insulinogenic index (insulin secretion); HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein. NC represents the number of individuals for each phenotype carrying any of the variants within that variant group. NN-C represents the number of individuals not carrying any of the variants within that variant group. q, FDR adjusted p-values of the burden tests (performed using SKAT/SKAT-O). Beta and error bars represent effect size as standard deviation and the 95% confidence interval, respectively, derived from a linear model.
