Dmitry Shungin1, Marilyn C Cornelis1, Kimon Divaris1, Birte Holtfreter1, John R Shaffer1, Yau-Hua Yu1, Silvana P Barros1, James D Beck1, Reiner Biffar1, Eric A Boerwinkle1, Richard J Crout1, Andrea Ganna1, Goran Hallmans1, George Hindy1, Frank B Hu1, Peter Kraft1, Daniel W McNeil1, Olle Melander1, Kevin L Moss1, Kari E North1, Marju Orho-Melander1, Nancy L Pedersen1, Paul M Ridker1, Eric B Rimm1, Lynda M Rose1, Gull Rukh1, Alexander Teumer1, Robert J Weyant1, Daniel I Chasman1, Kaumudi Joshipura1, Thomas Kocher1, Patrik K E Magnusson1, Mary L Marazita1, Peter Nilsson1, Steve Offenbacher1, George Davey Smith1, Pernilla Lundberg1, Tom M Palmer1, Nicholas J Timpson1, Ingegerd Johansson1, Paul W Franks1. 1. Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University, Umeå, Sweden, Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden, Department of Odontology, Umeå University, Umeå, Sweden, Department of Nutrition, Harvard School of Public Health, Boston, MA, USA, Department of Pediatric Dentistry, School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA, Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA, Department of Periodontology, and Department of Dental Ecology, School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA, Department of Prosthodontics, Gerodontology and Biomaterials, University Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany, Human Genetics Center, and Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA, Emeritus, Department of Periodontics, West Virginia University School of Dentistry, Morgantown, WV, USA, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Department of Biobank Research, Umeå University, Umeå, Sweden, Department of Clinical Sciences, Diabetes and Cardiovascular Disease Genetic Epidemiology, Lund University Diabetes Center, Skåne University Hosptial, Malmö, Sweden, Dental Practice and Rural Health, Morgantown, WV, USA, Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Lund University Diabetes Center, Skåne University Hospital, Malmö, Sweden, Department of
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.
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.
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