Figure 2.

a) Schematic representation of the Mendelian Randomization analysis results: genetic predisposition to higher abundance of butyrate-producing microbiome pathway PWY-5022 (4-aminobutanoate degradation V pathway) is associated with insulin response after glucose challenge. The causal effect of PWY-5022 was also seen on other insulin response parameters, and the forest plot in panel (b) represents the magnitude of the effect on each parameter per one-standard-deviation increase in pathway abundance, as estimated in the inverse-variance weighted Mendelian Randomization (MR) analysis. MR analysis was carried out using up to nine genetic predictors and their effect size from LL-DEEP (952 samples) and MAGIC summary statistics (trait specific sample sizes are: AUC_insulin/AUC_glucose = 4213; insulin at 30 min = 4,409; AUC_insulin = 4,324; correct insulin response = 4,789; insulin increase at 30 min = 4,447; Disposition index = 5,130) (Methods, Supplementary Table 4 and 5). Corresponding two-sided P-values are given in the annexed table. (c) Correlation plots with PWY-5022 abundance and the bacteria correlating the most with it in 950 LL-DEEP samples (subset of the 952 normo-glycemic samples for which presence of those bacteria was detected). The Spearman correlation coefficient ρ is given in blue in each panel.