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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 (US)
Article numberdyv075
Pages (from-to)638-650
Number of pages13
JournalInternational journal of epidemiology
Volume44
Issue number2
DOIs
StatePublished - May 27 2015

Keywords

  • BMI
  • Casual inference
  • Confounding
  • Mendelian randomization
  • Periodontitis

ASJC Scopus subject areas

  • Epidemiology

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