Shungin, DmitryCornelis, MarilynDivaris, KimonHoltfreter, BirteShaffer, JohnYu, Yau-HuaBarros, SilvanaBeck, JamesBiffar, ReinerBoerwinkle, EricCrout, RichardGanna, AndreaHallmans, GoranHindy, GeorgeHu, FrankKraft, PeterMcNeil, DanielMelander, OlleMoss, KevinNorth, KariOrho-Melander, MarjuPedersen, NancyRidker, PaulRimm, Eric Bruce::0ab2926c8242f35e5a982e3cf59f4987::600Rose, LyndaRukh, GullTeumer, AlexanderWeyant, RobertChasman, DanielJoshipura, KaumudiKocher, ThomasMagnusson, Patrik K. E.Marazita, MaryNilsson, PeterOffenbacher, SteveSmith, George DaveyLundberg, PernillaPalmer, TomTimpson, NicholasJohansson, IngegerdFranks, Paul2019-08-272015Shungin, D., M. C. Cornelis, K. Divaris, B. Holtfreter, J. R. Shaffer, Y.-H. Yu, S. P. Barros, et al. 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): 638–50. https://doi.org/10.1093/ije/dyv075.0300-57711464-3685http://nrs.harvard.edu/urn-3:HUL.InstRepos:41263058Background: 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.en-USJournal Article2019-08-2710.1093/ije/dyv075