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.
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in International Journal of Epidemiology following peer review. The definitive publisher-authenticated version 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 North, Marju 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 KE Magnusson, Mary L Marazita, Peter Nilsson, Steve Offenbacher, George Davey Smith, Pernilla Lundberg, Tom M Palmer, Nicholas J Timpson, Ingegerd Johansson, and Paul W Franks
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
Int. J. Epidemiol. (2015) 44 (2): 638-650 doi:10.1093/ije/dyv075 is available online at: http://ije.oxfordjournals.org/content/44/2/638.abstract