Junghyun Lim1, Janine Wirth2, Kana Wu3, Edward Giovannucci4, Peter Kraft5, Constance Turman5, Mingyang Song6, Manol Jovani7, Andrew T Chan8, Amit D Joshi9. 1. Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, Florida. 2. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; UCD Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Dublin, Ireland. 3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 5. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 6. Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 7. Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 8. Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 9. Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: adjoshi@mgh.harvard.edu.
Abstract
BACKGROUND & AIMS: Adiposity has been consistently associated with gallstone disease risk. We aimed to characterize associations of anthropometric measures (body mass index [BMI], recent weight change, long-term weight change, waist circumference, and waist-to-hip ratio) with symptomatic gallstone disease according to strata of gallstone disease polygenic risk score (PRS). METHODS: We conducted analysis among 34,626 participants with available genome-wide genetic data within 3 large, prospective, U.S. cohorts-the Nurses' Health Study (NHS), Health Professionals Follow-Up Study, and NHS II. We characterized joint associations of PRS and anthropometric measures and tested for interactions on the relative and absolute risk scales. RESULTS: Women in the highest BMI and PRS categories (BMI ≥30 kg/m2 and PRS ≥1 SD above mean) had odds ratio for gallstone disease of 5.55 (95% confidence interval, 5.29 to 5.81) compared with those in the lowest BMI and PRS categories (BMI <25 kg/m2 and PRS <1 SD below the mean). The corresponding odds ratio among men was 1.65 (95% confidence interval, 1.02 to 2.29). Associations for BMI did not vary within strata of PRS on the relative risk scale. On the absolute risk scale, the incidence rate difference between obese and normal-weight individuals was 1086 per 100,000 person-years within the highest PRS category, compared with 666 per 100,000 person-years in the lowest PRS category, with strong evidence for interaction with the ABCG8 locus. CONCLUSIONS: While maintenance of a healthy body weight reduces gallstone disease risk among all individuals, risk reduction is higher among the subset with greater genetic susceptibility to gallstone disease.
BACKGROUND & AIMS: Adiposity has been consistently associated with gallstone disease risk. We aimed to characterize associations of anthropometric measures (body mass index [BMI], recent weight change, long-term weight change, waist circumference, and waist-to-hip ratio) with symptomatic gallstone disease according to strata of gallstone disease polygenic risk score (PRS). METHODS: We conducted analysis among 34,626 participants with available genome-wide genetic data within 3 large, prospective, U.S. cohorts-the Nurses' Health Study (NHS), Health Professionals Follow-Up Study, and NHS II. We characterized joint associations of PRS and anthropometric measures and tested for interactions on the relative and absolute risk scales. RESULTS: Women in the highest BMI and PRS categories (BMI ≥30 kg/m2 and PRS ≥1 SD above mean) had odds ratio for gallstone disease of 5.55 (95% confidence interval, 5.29 to 5.81) compared with those in the lowest BMI and PRS categories (BMI <25 kg/m2 and PRS <1 SD below the mean). The corresponding odds ratio among men was 1.65 (95% confidence interval, 1.02 to 2.29). Associations for BMI did not vary within strata of PRS on the relative risk scale. On the absolute risk scale, the incidence rate difference between obese and normal-weight individuals was 1086 per 100,000 person-years within the highest PRS category, compared with 666 per 100,000 person-years in the lowest PRS category, with strong evidence for interaction with the ABCG8 locus. CONCLUSIONS: While maintenance of a healthy body weight reduces gallstone disease risk among all individuals, risk reduction is higher among the subset with greater genetic susceptibility to gallstone disease.
Authors: Summer S Han; Philip S Rosenberg; Montse Garcia-Closas; Jonine D Figueroa; Debra Silverman; Stephen J Chanock; Nathaniel Rothman; Nilanjan Chatterjee Journal: Am J Epidemiol Date: 2012-11-01 Impact factor: 4.897
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Authors: Amit D Joshi; Charlotte Andersson; Stephan Buch; Stefan Stender; Raymond Noordam; Lu-Chen Weng; Peter E Weeke; Paul L Auer; Bernhard Boehm; Constance Chen; Hyon Choi; Gary Curhan; Joshua C Denny; Immaculata De Vivo; John D Eicher; David Ellinghaus; Aaron R Folsom; Charles Fuchs; Manish Gala; Jeffrey Haessler; Albert Hofman; Frank Hu; David J Hunter; Harry L A Janssen; Jae H Kang; Charles Kooperberg; Peter Kraft; Wolfgang Kratzer; Wolfgang Lieb; Pamela L Lutsey; Sarwa Darwish Murad; Børge G Nordestgaard; Louis R Pasquale; Alex P Reiner; Paul M Ridker; Eric Rimm; Lynda M Rose; Christian M Shaffer; Clemens Schafmayer; Rulla M Tamimi; André G Uitterlinden; Uwe Völker; Henry Völzke; Yoshiyuki Wakabayashi; Janey L Wiggs; Jun Zhu; Dan M Roden; Bruno H Stricker; Weihong Tang; Alexander Teumer; Jochen Hampe; Anne Tybjærg-Hansen; Daniel I Chasman; Andrew T Chan; Andrew D Johnson Journal: Gastroenterology Date: 2016-04-16 Impact factor: 22.682