Using genetics to test the causal relationship of total adiposity and periodontitis: Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium

Dmitry Shungin, Marilyn C Cornelis, Kimon Divaris, Birte Holtfreter, John R Shaffer, Yau-Hua Yu, Silvana P Barros, James D Beck, Reiner Biffar, Eric A Boerwinkle, Richard J Crout, Andrea Ganna, Goran Hallmans, George Hindy, Frank B Hu, Peter Kraft, Daniel W McNeil, Olle Melander, Kevin L Moss, Kari E NorthMarju Orho-Melander, Nancy L Pedersen, Paul M Ridker, Eric B Rimm, Lynda M Rose, Gull Rukh, Alexander Teumer, Robert J Weyant, Daniel I Chasman, Kaumudi Joshipura, Thomas Kocher, Patrik K E Magnusson, Mary L Marazita, Peter Nilsson, Steve Offenbacher, George Davey Smith, Pernilla Lundberg, Tom M Palmer, Nicholas J Timpson, Ingegerd Johansson, Paul W Franks

Research output: Contribution to journalArticle (Academic Journal)peer-review

28 Citations (Scopus)

Abstract

BACKGROUND: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI).

METHODS: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49,066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17,672/31,394 with/without periodontitis); 68,761 participants with BMI and genotype data; and 57,871 participants (18,881/38,990 with/without periodontitis) with data on BMI and periodontitis.

RESULTS: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI:1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data.

CONCLUSIONS: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals.

Original languageEnglish
Pages (from-to)638-50
Number of pages13
JournalInternational Journal of Epidemiology
Volume44
Issue number2
DOIs
Publication statusPublished - Apr 2015

Keywords

  • Adiposity
  • Adult
  • Age Distribution
  • Aged
  • Body Mass Index
  • Cohort Studies
  • Female
  • Genotype
  • Humans
  • Life Style
  • Male
  • Membrane Proteins
  • Mendelian Randomization Analysis
  • Middle Aged
  • Obesity
  • Periodontitis
  • Polymorphism, Single Nucleotide
  • Proteins
  • Receptor, Melanocortin, Type 4
  • Young Adult
  • Journal Article
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

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