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Causal Effect of Genetic Variants Associated With Body Mass Index on Multiple Sclerosis Susceptibility.

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Authors
Gianfrancesco, Milena A
Glymour, M Maria
Walter, Stefan
Rhead, Brooke
Shao, Xiaorong
Shen, Ling
Quach, Hong
Hubbard, Alan
Jónsdóttir, Ingileif
Stefánsson, Kári
Strid, Pernilla
Hillert, Jan
Hedström, Anna
Olsson, Tomas
Kockum, Ingrid
Schaefer, Catherine
Alfredsson, Lars
Barcellos, Lisa F
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Issue Date
2017

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Causal Effect of Genetic Variants Associated With Body Mass Index on Multiple Sclerosis Susceptibility. 2017, 185 (3):162-171 Am. J. Epidemiol.
Abstract
Multiple sclerosis (MS) is an autoimmune disease with both genetic and environmental risk factors. Recent studies indicate that childhood and adolescent obesity double the risk of MS, but this association may reflect unmeasured confounders rather than causal effects of obesity. We used separate-sample Mendelian randomization to estimate the causal effect of body mass index (BMI) on susceptibility to MS. Using data from non-Hispanic white members of the Kaiser Permanente Medical Care Plan of Northern California (KPNC) (2006-2014; 1,104 cases of MS and 10,536 controls) and a replication data set from Sweden (the Epidemiological Investigation of MS (EIMS) and the Genes and Environment in MS (GEMS) studies, 2005-2013; 5,133 MS cases and 4,718 controls), we constructed a weighted genetic risk score using 97 variants previously established to predict BMI. Results were adjusted for birth year, sex, education, smoking status, ancestry, and genetic predictors of MS. Estimates in KPNC and Swedish data sets suggested that higher genetically induced BMI predicted greater susceptibility to MS (odds ratio = 1.13, 95% confidence interval: 1.04, 1.22 for the KPNC sample; odds ratio = 1.09, 95% confidence interval: 1.03, 1.15 for the Swedish sample). Although the mechanism remains unclear, to our knowledge, these findings support a causal effect of increased BMI on susceptibility to MS for the first time, and they suggest a role for inflammatory pathways that characterize both obesity and the MS disease process.
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https://academic.oup.com/aje/article/185/3/162/2877687
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Archived with thanks to American journal of epidemiology
ae974a485f413a2113503eed53cd6c53
10.1093/aje/kww120
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English Journal Articles (Peer Reviewed)

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