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Life-course adiposity and severe liver disease: a Mendelian randomization analysis
Xinyu Wang1, Zhiyu Wu1, Jun Lv1,2,3
1Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
Objective:
There is little evidence on the genetic associations between life-course adiposity (including birth weight, childhood BMI, and adulthood BMI) and severe liver disease (SLD; including cirrhosis and liver cancer). The current study aimed to examine and contrast these associations.
Methods:
Genetic variants were obtained from genome-wide association studies. Two-sample Mendelian randomization (MR) analyses were performed to assess the genetic associations of life-course adiposity with SLD and liver biomarkers. Cox regression was used to estimate adjusted hazard ratios for SLD associated with genetic risk scores of life-course adiposity and adulthood weight change in the China Kadoorie Biobank.
Results:
In observational analyses, genetic predispositions to childhood adiposity and adulthood adiposity were each associated with SLD. There was a U-shaped association between adulthood weight change and risk of SLD. In meta-analyses of MR results, genetically predicted 1-standard deviation increase in birth weight was inversely associated with SLD at a marginal significance (odds ratio: 0.81 [95% CI: 0.65-1.00]), whereas genetically predicted 1-standard deviation higher childhood BMI and adulthood BMI were positively associated with SLD (odds ratio: 1.27 [95% CI: 1.05-1.55] and 1.79 [95% CI: 1.59-2.01], respectively). The results of liver biomarkers mirrored those of SLD.
Conclusions:
The current study provided genetic evidence on the associations between life-course adiposity and SLD.
