Milena A Gianfrancesco1, Brigid Acuna2, Ling Shen2, Farren B S Briggs1, Hong Quach1, Kalliope H Bellesis2, Allan Bernstein3, Anna K Hedstrom4, Ingrid Kockum5, Lars Alfredsson6, Tomas Olsson5, Catherine Schaefer2, Lisa F Barcellos7. 1. Division of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, United States. 2. Kaiser Permanente Division of Research, Oakland, CA, United States. 3. Palm Drive Hospital, Sebastopol, CA, United States. 4. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 5. Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 6. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden. 7. Division of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, United States; Kaiser Permanente Division of Research, Oakland, CA, United States. Electronic address: lbarcellos@genepi.berkeley.edu.
Abstract
OBJECTIVE: To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. METHODS: Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. RESULTS: In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.60×10(-4)), and a twofold risk of MS for females with a BMI≥30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. INTERPRETATION: Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors.
OBJECTIVE: To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. METHODS:Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. RESULTS: In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.60×10(-4)), and a twofold risk of MS for females with a BMI≥30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. INTERPRETATION: Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors.
Authors: Lisa F Barcellos; Stephen Sawcer; Patricia P Ramsay; Sergio E Baranzini; Glenys Thomson; Farren Briggs; Bruce C A Cree; Ann B Begovich; Pablo Villoslada; Xavier Montalban; Antonio Uccelli; Giovanni Savettieri; Robin R Lincoln; Carolyn DeLoa; Jonathan L Haines; Margaret A Pericak-Vance; Alastair Compston; Stephen L Hauser; Jorge R Oksenberg Journal: Hum Mol Genet Date: 2006-08-11 Impact factor: 6.150
Authors: Chris H Polman; Stephen C Reingold; Gilles Edan; Massimo Filippi; Hans-Peter Hartung; Ludwig Kappos; Fred D Lublin; Luanne M Metz; Henry F McFarland; Paul W O'Connor; Magnhild Sandberg-Wollheim; Alan J Thompson; Brian G Weinshenker; Jerry S Wolinsky Journal: Ann Neurol Date: 2005-12 Impact factor: 10.422
Authors: Kassandra L Munger; Kira Hongell; Marianna Cortese; Julia Åivo; Merja Soilu-Hänninen; Heljä-Marja Surcel; Alberto Ascherio Journal: Ann Neurol Date: 2019-07-03 Impact factor: 10.422
Authors: Milena A Gianfrancesco; M Maria Glymour; Stefan Walter; Brooke Rhead; Xiaorong Shao; Ling Shen; Hong Quach; Alan Hubbard; Ingileif Jónsdóttir; Kári Stefánsson; Pernilla Strid; Jan Hillert; Anna Hedström; Tomas Olsson; Ingrid Kockum; Catherine Schaefer; Lars Alfredsson; Lisa F Barcellos Journal: Am J Epidemiol Date: 2017-02-01 Impact factor: 4.897
Authors: Milena A Gianfrancesco; Pernilla Stridh; Brooke Rhead; Xiaorong Shao; Edison Xu; Jennifer S Graves; Tanuja Chitnis; Amy Waldman; Timothy Lotze; Teri Schreiner; Anita Belman; Benjamin Greenberg; Bianca Weinstock-Guttman; Gregory Aaen; Jan M Tillema; Janace Hart; Stacy Caillier; Jayne Ness; Yolanda Harris; Jennifer Rubin; Meghan Candee; Lauren Krupp; Mark Gorman; Leslie Benson; Moses Rodriguez; Soe Mar; Ilana Kahn; John Rose; Shelly Roalstad; T Charles Casper; Ling Shen; Hong Quach; Diana Quach; Jan Hillert; Maria Bäärnhielm; Anna Hedstrom; Tomas Olsson; Ingrid Kockum; Lars Alfredsson; Catherine Metayer; Catherine Schaefer; Lisa F Barcellos; Emmanuelle Waubant Journal: Neurology Date: 2017-03-29 Impact factor: 9.910