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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.

TitleUsing genetics to test the causal relationship of total adiposity and periodontitis: Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium.
Publication TypeJournal Article
Year of Publication2015
AuthorsShungin D, Cornelis MC, Divaris K, Holtfreter B, Shaffer JR, Yu Y-H, Barros SP, Beck JD, Biffar R, Boerwinkle E, Crout RJ, Ganna A, Hallmans G, Hindy G, Hu FB, Kraft P, McNeil DW, Melander O, Moss KL, North KE, Orho-Melander M, Pedersen NL, Ridker PM, Rimm EB, Rose LM, Rukh G, Teumer A, Weyant RJ, Chasman DI, Joshipura K, Kocher T, Magnusson PKE, Marazita ML, Nilsson P, Offenbacher S, Smith GDavey, Lundberg P, Palmer TM, Timpson NJ, Johansson I
Secondary AuthorsFranks PW
JournalInt J Epidemiol
Volume44
Issue2
Pagination638-50
Date Published2015 Apr
ISSN1464-3685
KeywordsAdiposity, Adult, Age Distribution, Aged, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Mass Index, Cohort Studies, Female, Genotype, Humans, Life Style, Male, Membrane Proteins, Mendelian Randomization Analysis, Middle Aged, Obesity, Periodontitis, Polymorphism, Single Nucleotide, Proteins, Receptor, Melanocortin, Type 4, Young Adult
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.

DOI10.1093/ije/dyv075
Alternate JournalInt J Epidemiol
PubMed ID26050256
PubMed Central IDPMC4817600
Grant ListMC_UU_12013/3 / / Medical Research Council / United Kingdom
R01 DE014899 / DE / NIDCR NIH HHS / United States
MC_UU_12013/1 / / Medical Research Council / United Kingdom
R01 DE023836 / DE / NIDCR NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States