Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses
BackgroundGeneral 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.MethodsWe first investigated the observat...
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Frontiers Media S.A.
2024-03-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2024.1367229/full |
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| author | Min Zhang Ye Bai Yutong Wang Huijie Cui Wenqiang Zhang Li Zhang Peijing Yan Mingshuang Tang Yunjie Liu Xia Jiang Ben Zhang |
| author_facet | Min Zhang Ye Bai Yutong Wang Huijie Cui Wenqiang Zhang Li Zhang Peijing Yan Mingshuang Tang Yunjie Liu Xia Jiang Ben Zhang |
| author_sort | Min Zhang |
| collection | DOAJ |
| description | BackgroundGeneral 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.MethodsWe 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).ResultsObservational 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 (rg =0.41, P=1.42×10-52) was observed, driven by yet independent of BMI (WHRadjBMI: rg =0.19, P=6.89×10-16). 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 (rg =0.40, P=2.16×10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78).ConclusionBoth 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. |
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| spelling | doaj.art-000bc1b78b5343b1856ab5920a07c3f12024-03-11T04:43:40ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-03-011510.3389/fendo.2024.13672291367229Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analysesMin Zhang0Ye Bai1Yutong Wang2Huijie Cui3Wenqiang Zhang4Li Zhang5Peijing Yan6Mingshuang Tang7Yunjie Liu8Xia Jiang9Ben Zhang10Clinical and Public Health Research Center, Chongqing Research Center for Prevention & Control of Maternal and Child Diseases and Public Health, Chongqing Health Center for Women and Children, Women and Children’s Hospital of Chongqing Medical University, Chongqing, ChinaGene Diagnosis Center, the First Affiliated Hospital of Jilin University, Jilin, ChinaDepartment of Epidemiology and Health Statistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Epidemiology and Health Statistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Epidemiology and Health Statistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Epidemiology and Health Statistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Epidemiology and Health Statistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Epidemiology and Health Statistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Epidemiology and Health Statistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Epidemiology and Health Statistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Epidemiology and Health Statistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaBackgroundGeneral 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.MethodsWe 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).ResultsObservational 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 (rg =0.41, P=1.42×10-52) was observed, driven by yet independent of BMI (WHRadjBMI: rg =0.19, P=6.89×10-16). 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 (rg =0.40, P=2.16×10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78).ConclusionBoth 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.https://www.frontiersin.org/articles/10.3389/fendo.2024.1367229/fullgallstone diseasecentral obesityobservational associationgenetic correlationgenome-wide cross-trait analysis |
| spellingShingle | Min Zhang Ye Bai Yutong Wang Huijie Cui Wenqiang Zhang Li Zhang Peijing Yan Mingshuang Tang Yunjie Liu Xia Jiang Ben Zhang Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses Frontiers in Endocrinology gallstone disease central obesity observational association genetic correlation genome-wide cross-trait analysis |
| title | Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses |
| title_full | Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses |
| title_fullStr | Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses |
| title_full_unstemmed | Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses |
| title_short | Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses |
| title_sort | independent association of general and central adiposity with risk of gallstone disease observational and genetic analyses |
| topic | gallstone disease central obesity observational association genetic correlation genome-wide cross-trait analysis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1367229/full |
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