Dataset Information

Observational and Genetic Associations of Body Mass Index and Hepatobiliary Diseases in a Relatively Lean Chinese Population.

ABSTRACT: Importance:There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower. Objectives:To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases differed by hepatitis B virus infection status. Design, Setting, and Participants:This cohort study used data from the prospective China Kadoorie Biobank, including 473?938 adults aged 30 to 79 years without hepatobiliary diseases at baseline from 10 diverse areas in China from June 25, 2004, to July 15, 2008. A random sample of 75?736 participants with genotyping data was included in the Mendelian randomization analysis. Follow-up was completed January 1, 2017 (median [interquartile range] length of follow-up, 10.2 [9.2-11.1] years). Data were analyzed from January to October 2019. Exposures:Measured BMI obtained during the baseline survey and genetically instrumented BMI derived using 92 single-nucleotide variations. Main Outcomes and Measures:Incident cases of hepatobiliary diseases, liver enzymes, fatty liver index, and fibrosis score. Results:Among 473?938 individuals (276?041 [58.2%] women), the mean (SD) age was 52 (10.9) years and mean (SD) BMI was 23.8 (3.4). Baseline BMI was associated with higher risks of chronic liver disease (adjusted risk ratio per 1-SD increase, 1.14; 95% CI, 1.11 to 1.17) and gallbladder disease (adjusted risk ratio per 1-SD increase, 1.29; 95% CI, 1.27 to 1.31), with heterogeneity by disease subtype (P?

SUBMITTER: Pang Y

PROVIDER: S-EPMC7532388 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Observational and Genetic Associations of Body Mass Index and Hepatobiliary Diseases in a Relatively Lean Chinese Population.

Pang Yuanjie Y Kartsonaki Christiana C Lv Jun J Millwood Iona Y IY Yu Canqing C Guo Yu Y Chen Yiping Y Bian Zheng Z Yang Ling L Chen Junshi J Clarke Robert R Walters Robin R Wu Shukuan S Li Huimei H Holmes Michael V MV Li Liming L Chen Zhengming Z

JAMA network open 20201001 10

<h4>Importance</h4>There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower.<h4>Objectives</h4>To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic asso ...[more]

PMID: 33006619

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Project description:The TOMM40-APOE variants are known for their strong, antagonistic associations with Alzheimer's disease and body weight. While a stronger role of the APOE than TOMM40 variants in Alzheimer's disease was suggested, comparative contribution of the TOMM40-APOE variants in the regulation of body weight remains elusive. We examined additive effects of rs2075650 and rs157580 TOMM40 variants and rs429358 and rs7412 APOE variants coding the ?2/?3/?4 polymorphism on body mass index (BMI) in age-aggregated and age-stratified cohort-specific and cohort-pooled analysis of 27,863 Caucasians aged 20-100 years from seven longitudinal studies. Minor alleles of rs2075650, rs429358, and rs7412 were individually associated with BMI (? = -1.29, p = 3.97 × 10-9 ; ? = -1.38, p = 2.78 × 10-10 ; and ? = 0.58, p = 3.04 × 10-2 , respectively). Conditional analysis with rs2075650 and rs429358 identified independent BMI-lowering associations for minor alleles (? = -0.63, p = 3.99 × 10-2 and ? = -0.94, p = 2.17 × 10-3 , respectively). Polygenic mega-analysis identified additive effects of the rs2075650 and rs429358 heterozygotes (? = -1.68, p = 3.00 × 10-9 ), and the strongest BMI-lowering association for the rs2075650 heterozygous and rs429358 minor allele homozygous carriers (? = -4.11, p = 2.78 × 10-3 ). Conditional analysis with four polymorphisms identified independent BMI-lowering (rs2075650, rs157580, and rs429358) and BMI-increasing (rs7412) associations of heterozygous genotypes with BMI. Age-stratified conditional analysis revealed well-powered support for a differential and independent association of the rs429358 heterozygote with BMI in younger and older individuals, ? = 0.58, 95% confidence interval (CI) = -1.18, 2.35, p = 5.18 × 10-1 for 3,068 individuals aged ?30 years and ? = -4.28, CI = -5.65, -2.92, p = 7.71 × 10-10 for 6,052 individuals aged >80 years. TOMM40 and APOE variants are independently and additively associated with BMI. The APOE ?4-coding rs429358 polymorphism is associated with BMI in older individuals but not in younger individuals.

Dataset Information

Observational and Genetic Associations of Body Mass Index and Hepatobiliary Diseases in a Relatively Lean Chinese Population.

Publications

Observational and Genetic Associations of Body Mass Index and Hepatobiliary Diseases in a Relatively Lean Chinese Population.

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