Fig. 3: Damaging mutations in LXRα are associated with elevated liver enzymes despite beneficial effects on lipid metabolism. | Nature Metabolism

Fig. 3: Damaging mutations in LXRα are associated with elevated liver enzymes despite beneficial effects on lipid metabolism.

From: Damaging mutations in liver X receptor-α are hepatotoxic and implicate cholesterol sensing in liver health

Fig. 3

a, Forest plot illustrating the effects of carriage of a damaging mutation in LXRα (DN or LOF bioinformatically predicted PTVs) on a selection of cardiometabolic traits in European participants in the UKBB. Each dot represents the effect of a damaging mutation on the trait in s.d., the error bars represent 95% CIs, each derived from a generalized linear model (Methods). Red points indicate statistical significance after correction for multiple testing using the Bonferroni method (P < 3.9 × 10−4), NS, not significant. b, Scatter-plot illustrating the relationship between LXRα mutant activity and HDL cholesterol. Each dot represents an individual mutation, the size of the dot is proportional to number of carriers included in the analysis and weight in the model. The solid black line and grey band represent the estimated mean (± 95% CIs) effect of changes in LXRα activity on HDL cholesterol derived from a weighted regression analysis. c, Volcano plot illustrating the effect of damaging mutations (LOF or DN or PTV) in LXRα on lipoprotein particle size and composition assessed by nuclear magnetic resonance using the Nightingale health platform in UKBB. A full list of abbreviations for lipid measurements in c are available in Supplementary Table 10. The dotted line represents the Bonferroni-adjusted P value cutoff (P < 5.7 × 10−4). d, Forest plot illustrating the effect of damaging mutations in LXRα on liver disease and liver fat in UKBB. Each dot represents the effect of a damaging mutation on the trait in s.d. if continuous or log(odds) if binary, the error bars represent 95% CIs. LP(a), lipoprotein-a; BMI, body mass index; WHR adj BMI, waist hip ratio adjusted for BMI; ALP, alkaline phosphatase; GGT, γ glutamyl transferase; ApoA1, apolipoprotein A1; NAFLD, non-alcoholic fatty liver disease; ARLD, alcohol-related liver disease. P values are two-sided. Burden P values were calculated in STAAR (Methods).

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