Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses

作者全名："Zhang, Min; Bai, Ye; Wang, Yutong; Cui, Huijie; Zhang, Wenqiang; Zhang, Li; Yan, Peijing; Tang, Mingshuang; Liu, Yunjie; Jiang, Xia; Zhang, Ben"

作者地址："[Zhang, Min] Chongqing Med Univ, Women & Childrens Hosp, Chongqing Res Ctr Prevent & Control Maternal & Chi, Chongqing Hlth Ctr Women & Children,Clin & Publ Hl, Chongqing, Peoples R China; [Bai, Ye] Jilin Univ, Affiliated Hosp 1, Gene Diag Ctr, Jilin, Peoples R China; [Wang, Yutong; Cui, Huijie; Zhang, Wenqiang; Zhang, Li; Yan, Peijing; Tang, Mingshuang; Liu, Yunjie; Jiang, Xia; Zhang, Ben] Sichuan Univ, Inst Syst Epidemiol, Dept Epidemiol & Hlth Stat, Chengdu, Sichuan, Peoples R China; [Wang, Yutong; Cui, Huijie; Zhang, Wenqiang; Zhang, Li; Yan, Peijing; Tang, Mingshuang; Liu, Yunjie; Jiang, Xia; Zhang, Ben] Sichuan Univ, West China PUMC C C Chen Inst Hlth, Chengdu, Sichuan, Peoples R China; [Wang, Yutong; Cui, Huijie; Zhang, Wenqiang; Zhang, Li; Yan, Peijing; Tang, Mingshuang; Liu, Yunjie; Jiang, Xia; Zhang, Ben] Sichuan Univ, West China Hosp 4, Chengdu, Sichuan, Peoples R China"

通信作者："Jiang, X; Zhang, B (通讯作者)，Sichuan Univ, West China PUMC C C Chen Inst Hlth, Chengdu, Sichuan, Peoples R China.; Jiang, X; Zhang, B (通讯作者)，Sichuan Univ, West China Hosp 4, Chengdu, Sichuan, Peoples R China."

来源：FRONTIERS IN ENDOCRINOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001189653300001

JCR分区：Q2

影响因子：3.9

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：gallstone disease; central obesity; observational association; genetic correlation; genome-wide cross-trait analysis

摘要："Background General obesity is a well-established risk factor for gallstone disease (GSD), but whether central obesity contributes additional independent risk remains controversial. We aimed to comprehensively clarify the effect of body fat distribution on GSD.Methods We first investigated the observational association of central adiposity, characterized by waist-to-hip ratio (WHR), with GSD risk using data from UK Biobank (N=472,050). We then explored the genetic relationship using summary statistics from the largest genome-wide association study of GSD (ncase =43,639, ncontrol =506,798) as well as WHR, with and without adjusting for body mass index (BMI) (WHR: n=697,734; WHRadjBMI: n=694,649).Results Observational analysis demonstrated an increased risk of GSD with one unit increase in WHR (HR=1.18, 95%CI=1.14-1.21). A positive WHR-GSD genetic correlation ( r g =0.41, P=1.42x10-52) was observed, driven by yet independent of BMI (WHRadjBMI: r g =0.19, P=6.89x10-16). Cross-trait meta-analysis identified four novel pleiotropic loci underlying WHR and GSD with biological mechanisms outside of BMI. Mendelian randomization confirmed a robust WHR-GSD causal relationship (OR=1.50, 95%CI=1.35-1.65) which attenuated yet remained significant after adjusting for BMI (OR=1.17, 95%CI=1.09-1.26). Furthermore, observational analysis confirmed a positive association between general obesity and GSD, corroborated by a shared genetic basis ( r g =0.40, P=2.16x10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78).Conclusion Both observational and genetic analyses consistently provide evidence on an association of central obesity with an increased risk of GSD, independent of general obesity. Our work highlights the need of considering both general and central obesity in the clinical management of GSD."

基金机构："National Key R&D Program of China [2022YFC3600600, 2022YFC3600604]; National Natural Science Foundation of China [U22A20359, 81874283, 81673255]; Chongqing Research Centre for Prevention & Control of Maternal and Child Diseases and Public Health [CQFYJB01004]"

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the National Key R & D Program of China (2022YFC3600600, 2022YFC3600604), the National Natural Science Foundation of China (U22A20359, 81874283, 81673255),and the Chongqing Research Centre for Prevention & Control of Maternal and Child Diseases and Public Health (CQFYJB01004).The funding agencies of the current study had no role in study design, data collection, data management, data analysis, data interpretation, writing of the manuscript, or submission decision."