PMID- 27351487
OWN - NLM
STAT- MEDLINE
DCOM- 20170531
LR  - 20230315
IS  - 1549-1676 (Electronic)
IS  - 1549-1277 (Print)
IS  - 1549-1277 (Linking)
VI  - 13
IP  - 6
DP  - 2016 Jun
TI  - Obesity and Multiple Sclerosis: A Mendelian Randomization Study.
PG  - e1002053
LID - 10.1371/journal.pmed.1002053 [doi]
LID - e1002053
AB  - BACKGROUND: Observational studies have reported an association between obesity, 
      as measured by elevated body mass index (BMI), in early adulthood and risk of 
      multiple sclerosis (MS). However, bias potentially introduced by confounding and 
      reverse causation may have influenced these findings. Therefore, we elected to 
      perform Mendelian randomization (MR) analyses to evaluate whether genetically 
      increased BMI is associated with an increased risk of MS. METHODS AND FINDINGS: 
      Employing a two-sample MR approach, we used summary statistics from the Genetic 
      Investigation of Anthropometric Traits (GIANT) consortium and the International 
      MS Genetics Consortium (IMSGC), the largest genome-wide association studies for 
      BMI and MS, respectively (GIANT: n = 322,105; IMSGC: n = 14,498 cases and 24,091 
      controls). Seventy single nucleotide polymorphisms (SNPs) were genome-wide 
      significant (p < 5 x 10-8) for BMI in GIANT (n = 322,105) and were investigated 
      for their association with MS risk in the IMSGC. The effect of each SNP on MS was 
      weighted by its effect on BMI, and estimates were pooled to provide a summary 
      measure for the effect of increased BMI upon risk of MS. Our results suggest that 
      increased BMI influences MS susceptibility, where a 1 standard deviation increase 
      in genetically determined BMI (kg/m2) increased odds of MS by 41% (odds ratio 
      [OR]: 1.41, 95% CI 1.20-1.66, p = 2.7 x 10-5, I2 = 0%, 95% CI 0-29). Sensitivity 
      analyses, including MR-Egger regression, and the weighted median approach 
      provided no evidence of pleiotropic effects. The main study limitations are that, 
      while these sensitivity analyses reduce the possibility that pleiotropy 
      influenced our results, residual pleiotropy is difficult to exclude entirely. 
      CONCLUSION: Genetically elevated BMI is associated with risk of MS, providing 
      evidence for a causal role for obesity in MS etiology. While obesity has been 
      associated with many late-life outcomes, these findings suggest an important 
      consequence of childhood and/or early adulthood obesity.
FAU - Mokry, Lauren E
AU  - Mokry LE
AD  - Department of Epidemiology, Biostatistics and Occupational Health, McGill 
      University, Montreal, Quebec, Canada.
AD  - Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis 
      Institute for Medical Research, Jewish General Hospital, McGill University, 
      Montreal, Quebec, Canada.
FAU - Ross, Stephanie
AU  - Ross S
AD  - Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis 
      Institute for Medical Research, Jewish General Hospital, McGill University, 
      Montreal, Quebec, Canada.
FAU - Timpson, Nicholas J
AU  - Timpson NJ
AUID- ORCID: 0000-0002-7141-9189
AD  - MRC Integrative Epidemiology Unit, School of Social and Community Medicine, 
      University of Bristol, Bristol, United Kingdom.
FAU - Sawcer, Stephen
AU  - Sawcer S
AUID- ORCID: 0000-0001-7685-0974
AD  - Department of Clinical Neurosciences, Cambridge Biomedical Campus, Cambridge, 
      United Kingdom.
FAU - Davey Smith, George
AU  - Davey Smith G
AD  - MRC Integrative Epidemiology Unit, School of Social and Community Medicine, 
      University of Bristol, Bristol, United Kingdom.
FAU - Richards, J Brent
AU  - Richards JB
AD  - Department of Epidemiology, Biostatistics and Occupational Health, McGill 
      University, Montreal, Quebec, Canada.
AD  - Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis 
      Institute for Medical Research, Jewish General Hospital, McGill University, 
      Montreal, Quebec, Canada.
AD  - Department of Medicine, McGill University, Montreal, Quebec, Canada.
AD  - Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
AD  - Department of Twin Research and Genetic Epidemiology, King's College London, 
      London, United Kingdom.
LA  - eng
GR  - CIHR/Canada
GR  - 202802/Z/16/Z/WT_/Wellcome Trust/United Kingdom
GR  - MC_UU_12013/3/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_12013/1/MRC_/Medical Research Council/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160628
PL  - United States
TA  - PLoS Med
JT  - PLoS medicine
JID - 101231360
SB  - IM
CIN - PLoS Med. 2016 Jun 28;13(6):e1002054. PMID: 27351631
MH  - Body Mass Index
MH  - Genome-Wide Association Study
MH  - Humans
MH  - *Mendelian Randomization Analysis
MH  - Multiple Sclerosis/*etiology
MH  - Obesity/*complications/*genetics
MH  - Odds Ratio
MH  - Polymorphism, Single Nucleotide
PMC - PMC4924848
COIS- GDS is a member of the Editorial Board of PLOS Medicine. The other authors 
      declare that no competing interests exist.
EDAT- 2016/06/29 06:00
MHDA- 2017/06/01 06:00
PMCR- 2016/06/28
CRDT- 2016/06/29 06:00
PHST- 2016/01/19 00:00 [received]
PHST- 2016/05/17 00:00 [accepted]
PHST- 2016/06/29 06:00 [entrez]
PHST- 2016/06/29 06:00 [pubmed]
PHST- 2017/06/01 06:00 [medline]
PHST- 2016/06/28 00:00 [pmc-release]
AID - PMEDICINE-D-16-00214 [pii]
AID - 10.1371/journal.pmed.1002053 [doi]
PST - epublish
SO  - PLoS Med. 2016 Jun 28;13(6):e1002053. doi: 10.1371/journal.pmed.1002053. 
      eCollection 2016 Jun.