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

Shungin, Dmitry and Cornelis, Marilyn C. and Divaris, Kimon and Holtfreter, Birte and Shaffer, John R. and Yu, Yau-Hua and Barros, Silvana P and Beck, James D. and Biffar, Reiner and Boerwinkle, Eric A. and Crout, Richard J. and Ganna, Andrea and Hallmans, Goran and Hindy, George and Hu, Frank B. and Kraft, Peter and McNeil, Daniel W. and Melander, Olle and Moss, Kevin L. and North, Kari E. and Orho-Melander, Marju and Pedersen, Nancy L. and Ridker, Paul M. and Rimm, Eric B. and Rose, Lynda M. and Rukh, Gull and Teumer, Alexander and Weyant, Robert J. and Chasman, Daniel I. and Joshipura, Kaumudi and Kocher, Thomas and Magnusson, Patrik K. E. and Marazita, Mary L. and Nilsson, Peter and Offenbacher, Steve and Davey Smith, George and Lundberg, Pernilla and Palmer, Tom M. and Timpson, Nicholas J. and Johansson, Ingegerd and Franks, Paul W. (2015) 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. International Journal of Epidemiology, 44 (2). pp. 638-650. ISSN 0300-5771

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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.

Item Type:
Journal Article
Journal or Publication Title:
International Journal of Epidemiology
Additional Information:
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
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2713
Subjects:
ID Code:
76808
Deposited By:
Deposited On:
24 Nov 2015 12:00
Refereed?:
Yes
Published?:
Published
Last Modified:
18 Oct 2020 02:21