Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

Dmitry Shungin; Simon Haworth; Kimon Divaris; Cary Agler; Yoichiro Kamatani; Myoung Keun Lee; Kelsey  Grinde; George Hindy; Viivi Viivi Alaraudanjoki; Paula  Pesonen; Alexander Teumer; Birte Holtfreter; Saori Sakaue; Jun Hirata; Yau-Hua Yu; Paul Ridker; Franco Giulianini; Daniel I. Chasman; Patrik K E Magnusson; Takeaki Sudo; Yukinori Okada; Uwe Völker; Thomas Kocher; Vuokko Anttonen; Marja-Liisa Laitala; Marji Orho-Melander; Tamar Sofer; John R Shaffer; Alexandre Vieira; Mary L Marazita; Michiaki Kubo; Yasushi Furuichi; Kari North; Steve Offenbacher; Erik Ingelsson; Paul W Franks; Nicholas Timpson; Ingegerd Johansson

doi:10.1038/s41467-019-10630-1

Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

Dmitry Shungin, Simon Haworth, Kimon Divaris, Cary Agler, Yoichiro Kamatani, Myoung Keun Lee, Kelsey Grinde, George Hindy, Viivi Viivi Alaraudanjoki, Paula Pesonen, Alexander Teumer, Birte Holtfreter, Saori Sakaue, Jun Hirata, Yau-Hua Yu, Paul Ridker, Franco Giulianini, Daniel I. Chasman, Patrik K E Magnusson, Takeaki SudoYukinori Okada, Uwe Völker, Thomas Kocher, Vuokko Anttonen, Marja-Liisa Laitala, Marji Orho-Melander, Tamar Sofer, John R Shaffer, Alexandre Vieira, Mary L Marazita, Michiaki Kubo, Yasushi Furuichi, Kari North, Steve Offenbacher, Erik Ingelsson, Paul W Franks, Nicholas Timpson, Ingegerd Johansson

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Abstract

Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example, in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.

Original language	English
Article number	2773
Number of pages	13
Journal	Nature Communications
Volume	10
DOIs	https://doi.org/10.1038/s41467-019-10630-1
Publication status	Published - 24 Jun 2019

Keywords

Dental Caries/epidemiology
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomics
Heredity
Humans
Mendelian Randomization Analysis
Periodontitis/epidemiology
Polymorphism, Single Nucleotide
Quantitative Trait Loci/genetics
Self Report/statistics & numerical data

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10.1038/s41467-019-10630-1

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Shungin, D., Haworth, S., Divaris, K., Agler, C., Kamatani, Y., Lee, M. K., Grinde, K., Hindy, G., Viivi Alaraudanjoki, V., Pesonen, P., Teumer, A., Holtfreter, B., Sakaue, S., Hirata, J., Yu, Y.-H., Ridker, P., Giulianini, F., Chasman, D. I., Magnusson, P. K. E., ... Johansson, I. (2019). Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data. Nature Communications, 10, Article 2773. https://doi.org/10.1038/s41467-019-10630-1

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title = "Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data",

abstract = "Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example, in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health. ",

keywords = "Dental Caries/epidemiology, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Heredity, Humans, Mendelian Randomization Analysis, Periodontitis/epidemiology, Polymorphism, Single Nucleotide, Quantitative Trait Loci/genetics, Self Report/statistics & numerical data",

author = "Dmitry Shungin and Simon Haworth and Kimon Divaris and Cary Agler and Yoichiro Kamatani and Lee, {Myoung Keun} and Kelsey Grinde and George Hindy and {Viivi Alaraudanjoki}, Viivi and Paula Pesonen and Alexander Teumer and Birte Holtfreter and Saori Sakaue and Jun Hirata and Yau-Hua Yu and Paul Ridker and Franco Giulianini and Chasman, {Daniel I.} and Magnusson, {Patrik K E} and Takeaki Sudo and Yukinori Okada and Uwe V{\"o}lker and Thomas Kocher and Vuokko Anttonen and Marja-Liisa Laitala and Marji Orho-Melander and Tamar Sofer and Shaffer, {John R} and Alexandre Vieira and Marazita, {Mary L} and Michiaki Kubo and Yasushi Furuichi and Kari North and Steve Offenbacher and Erik Ingelsson and Franks, {Paul W} and Nicholas Timpson and Ingegerd Johansson",

year = "2019",

month = jun,

day = "24",

doi = "10.1038/s41467-019-10630-1",

language = "English",

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journal = "Nature Communications",

issn = "2041-1723",

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Shungin, D, Haworth, S, Divaris, K, Agler, C, Kamatani, Y, Lee, MK, Grinde, K, Hindy, G, Viivi Alaraudanjoki, V, Pesonen, P, Teumer, A, Holtfreter, B, Sakaue, S, Hirata, J, Yu, Y-H, Ridker, P, Giulianini, F, Chasman, DI, Magnusson, PKE, Sudo, T, Okada, Y, Völker, U, Kocher, T, Anttonen, V, Laitala, M-L, Orho-Melander, M, Sofer, T, Shaffer, JR, Vieira, A, Marazita, ML, Kubo, M, Furuichi, Y, North, K, Offenbacher, S, Ingelsson, E, Franks, PW, Timpson, N & Johansson, I 2019, 'Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data', Nature Communications, vol. 10, 2773. https://doi.org/10.1038/s41467-019-10630-1

TY - JOUR

T1 - Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

AU - Shungin, Dmitry

AU - Haworth, Simon

AU - Divaris, Kimon

AU - Agler, Cary

AU - Kamatani, Yoichiro

AU - Lee, Myoung Keun

AU - Grinde, Kelsey

AU - Hindy, George

AU - Viivi Alaraudanjoki, Viivi

AU - Pesonen, Paula

AU - Teumer, Alexander

AU - Holtfreter, Birte

AU - Sakaue, Saori

AU - Hirata, Jun

AU - Yu, Yau-Hua

AU - Ridker, Paul

AU - Giulianini, Franco

AU - Chasman, Daniel I.

AU - Magnusson, Patrik K E

AU - Sudo, Takeaki

AU - Okada, Yukinori

AU - Völker, Uwe

AU - Kocher, Thomas

AU - Anttonen, Vuokko

AU - Laitala, Marja-Liisa

AU - Orho-Melander, Marji

AU - Sofer, Tamar

AU - Shaffer, John R

AU - Vieira, Alexandre

AU - Marazita, Mary L

AU - Kubo, Michiaki

AU - Furuichi, Yasushi

AU - North, Kari

AU - Offenbacher, Steve

AU - Ingelsson, Erik

AU - Franks, Paul W

AU - Timpson, Nicholas

AU - Johansson, Ingegerd

PY - 2019/6/24

Y1 - 2019/6/24

N2 - Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example, in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.

AB - Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example, in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.

KW - Dental Caries/epidemiology

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genomics

KW - Heredity

KW - Humans

KW - Mendelian Randomization Analysis

KW - Periodontitis/epidemiology

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci/genetics

KW - Self Report/statistics & numerical data

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U2 - 10.1038/s41467-019-10630-1

DO - 10.1038/s41467-019-10630-1

M3 - Article (Academic Journal)

C2 - 31235808

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

M1 - 2773

ER -

Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

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GWAS summary statistics for dental caries and periodontitis

Professor Nicholas John Timpson

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Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

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GWAS summary statistics for dental caries and periodontitis

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Professor Nicholas John Timpson

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