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

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 K E Magnusson; Mary L Marazita; Peter Nilsson; Steve Offenbacher; George Davey Smith; Pernilla Lundberg; Tom M Palmer; Nicholas J Timpson; Ingegerd Johansson; Paul W Franks

doi:10.1093/ije/dyv075

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

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 NorthMarju 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 K E Magnusson, Mary L Marazita, Peter Nilsson, Steve Offenbacher, George Davey Smith, Pernilla Lundberg, Tom M Palmer, Nicholas J Timpson, Ingegerd Johansson, Paul W Franks

Research output: Contribution to journal › Article (Academic Journal) › peer-review

47 Citations (Scopus)

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.

Original language	English
Pages (from-to)	638-50
Number of pages	13
Journal	International Journal of Epidemiology
Volume	44
Issue number	2
DOIs	https://doi.org/10.1093/ije/dyv075
Publication status	Published - Apr 2015

Keywords

Adiposity
Adult
Age Distribution
Aged
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
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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MRC UoB UNITE Unit - Programme 1
Davey Smith, G.
1/06/13 → 31/03/18
Project: Research
MRC UoB UNITE Unit - programme 3
Timpson, N. J. & Timpson, N. J.
1/06/13 → 31/03/18
Project: Research

Cite this

Shungin, D., Cornelis, M. C., Divaris, K., Holtfreter, B., Shaffer, J. R., Yu, Y-H., Barros, S. P., Beck, J. D., Biffar, R., Boerwinkle, E. A., Crout, R. J., Ganna, A., Hallmans, G., Hindy, G., Hu, F. B., Kraft, P., McNeil, D. W., Melander, O., Moss, K. L., ... Franks, P. 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), 638-50. https://doi.org/10.1093/ije/dyv075

@article{03618e21d6e34f0f9cffe52672b4e906,

title = "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",

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.",

keywords = "Adiposity, Adult, Age Distribution, Aged, 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, Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't",

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

year = "2015",

month = apr,

doi = "10.1093/ije/dyv075",

language = "English",

volume = "44",

pages = "638--50",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "2",

}

Shungin, D, Cornelis, MC, Divaris, K, Holtfreter, B, Shaffer, JR, Yu, Y-H, Barros, SP, Beck, JD, Biffar, R, Boerwinkle, EA, 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, Davey Smith, G, Lundberg, P, Palmer, TM , Timpson, NJ, Johansson, I & Franks, PW 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, vol. 44, no. 2, pp. 638-50. https://doi.org/10.1093/ije/dyv075

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; Cornelis, Marilyn C; Divaris, Kimon et al.
In: International Journal of Epidemiology, Vol. 44, No. 2, 04.2015, p. 638-50.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Using genetics to test the causal relationship of total adiposity and periodontitis

T2 - Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium

AU - Shungin, Dmitry

AU - Cornelis, Marilyn C

AU - Divaris, Kimon

AU - Holtfreter, Birte

AU - Shaffer, John R

AU - Yu, Yau-Hua

AU - Barros, Silvana P

AU - Beck, James D

AU - Biffar, Reiner

AU - Boerwinkle, Eric A

AU - Crout, Richard J

AU - Ganna, Andrea

AU - Hallmans, Goran

AU - Hindy, George

AU - Hu, Frank B

AU - Kraft, Peter

AU - McNeil, Daniel W

AU - Melander, Olle

AU - Moss, Kevin L

AU - North, Kari E

AU - Orho-Melander, Marju

AU - Pedersen, Nancy L

AU - Ridker, Paul M

AU - Rimm, Eric B

AU - Rose, Lynda M

AU - Rukh, Gull

AU - Teumer, Alexander

AU - Weyant, Robert J

AU - Chasman, Daniel I

AU - Joshipura, Kaumudi

AU - Kocher, Thomas

AU - Magnusson, Patrik K E

AU - Marazita, Mary L

AU - Nilsson, Peter

AU - Offenbacher, Steve

AU - Davey Smith, George

AU - Lundberg, Pernilla

AU - Palmer, Tom M

AU - Timpson, Nicholas J

AU - Johansson, Ingegerd

AU - Franks, Paul W

PY - 2015/4

Y1 - 2015/4

N2 - 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.

AB - 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.

KW - Adiposity

KW - Adult

KW - Age Distribution

KW - Aged

KW - Body Mass Index

KW - Cohort Studies

KW - Female

KW - Genotype

KW - Humans

KW - Life Style

KW - Male

KW - Membrane Proteins

KW - Mendelian Randomization Analysis

KW - Middle Aged

KW - Obesity

KW - Periodontitis

KW - Polymorphism, Single Nucleotide

KW - Proteins

KW - Receptor, Melanocortin, Type 4

KW - Young Adult

KW - Journal Article

KW - Meta-Analysis

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/ije/dyv075

DO - 10.1093/ije/dyv075

M3 - Article (Academic Journal)

C2 - 26050256

SN - 0300-5771

VL - 44

SP - 638

EP - 650

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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