Genome-Wide Association Study (GWAS) of dental caries in diverse populations

Rasha N Alotaibi; Brian J Howe; Jonathan M Chernus; Nandita Mukhopadhyay; Carla Sanchez; Frederic W B Deleyiannis; Katherine Neiswanger; Carmencita Padilla; Fernando A Poletta; Ieda M Orioli; Carmen J Buxó; Jacqueline T Hecht; George L Wehby; Ross E Long; Alexandre R Vieira; Seth M Weinberg; John R Shaffer; Lina M Moreno Uribe; Mary L Marazita

doi:10.1186/s12903-021-01670-5

Genome-Wide Association Study (GWAS) of dental caries in diverse populations

BMC Oral Health. 2021 Jul 26;21(1):377. doi: 10.1186/s12903-021-01670-5.

Authors

Rasha N Alotaibi^{1

2

3}, Brian J Howe^{4

5}, Jonathan M Chernus^{6

7}, Nandita Mukhopadhyay^{6

8}, Carla Sanchez^{6

8}, Frederic W B Deleyiannis⁹, Katherine Neiswanger^{6

8}, Carmencita Padilla¹⁰, Fernando A Poletta¹¹, Ieda M Orioli¹², Carmen J Buxó¹³, Jacqueline T Hecht¹⁴, George L Wehby¹⁵, Ross E Long¹⁶, Alexandre R Vieira⁶, Seth M Weinberg^{6

8}, John R Shaffer^{6

8

7}, Lina M Moreno Uribe^{4

17}, Mary L Marazita^{6

8

7}

Affiliations

¹ Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA. rnasha@ksu.edu.sa.
² Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA. rnasha@ksu.edu.sa.
³ Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia. rnasha@ksu.edu.sa.
⁴ Department of Family Dentistry, College of Dentistry, University of Iowa, Iowa City, IA, USA.
⁵ The Iowa Center for Oral Health Research, College of Dentistry, University of Iowa, Iowa City, IA, USA.
⁶ Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ UC Health Medical Group, Colorado Springs, Denver, CO, USA.
¹⁰ Department of Pediatrics, College of Medicine, University of the Philippines, Manila, Philippines.
¹¹ ECLAMC/INAGEMP At Center for Medical Education and Clinical Research (CEMIC-CONICET), Buenos Aires, Argentina.
¹² Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹³ Dental and Craniofacial Genomics Core, School of Dental Medicine, University of Puerto Rico, San Juan, PR, USA.
¹⁴ Department of Pediatrics, University of Texas Health Science Center At Houston, Houston, TX, USA.
¹⁵ Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City, IA, USA.
¹⁶ Lancaster Cleft Palate Clinic, Lancaster, PA, USA.
¹⁷ Department of Orthodontics, School of Dentistry, University of Iowa, Iowa City, IA, USA.

Abstract

Background: Dental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent.

Methods: The aim of this study is to conduct a genome-wide association study (GWAS) to identify associations affecting susceptibility to caries in a large multiethnic population from Argentina, the Philippines, Guatemala, Hungary, and the USA, originally recruited for studies of orofacial clefts (POFC, N = 3686). Ages of the participants ranged from 2 to 12 years for analysis of the primary dentition, and 18-60 years for analysis of the permanent dentition. For each participant, dental caries was assessed by counts of decayed and filled teeth (dft/DFT) and genetic variants (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Caries was analyzed separately for the primary and permanent dentitions, with age, gender, and presence/absence of any type of OFC treated as covariates. Efficient Mixed-Model Association eXpedited (EMMAX) was used to test genetic association, while simultaneously accounting for relatedness and stratification.

Results: We identified several suggestive loci (5 × 10^-8 < P < 5 × 10^-6) within or near genes with plausible biological roles for dental caries, including a cluster of taste receptor genes (TAS2R38, TAS2R3, TAS2R4, TASR25) on chromosome 7 for the permanent dentition analysis, and DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. Genome-wide significant results were seen with SNPs in the primary dentition only; however, none of the identified genes near these variants have known roles in cariogenesis.

Conclusion: The results of this study warrant further investigation and may lead to a better understanding of cariogenesis in diverse populations, and help to improve dental caries prediction, prevention, and/or treatment in future.

Keywords: Dental caries; Ethnicity; Genetics; Genomics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Child
Child, Preschool
Cleft Lip*
Cleft Palate*
DMF Index
Dental Caries* / epidemiology
Dental Caries* / genetics
Female
Genome-Wide Association Study
Homeodomain Proteins
Humans
Male
Middle Aged
Philippines
Transcription Factors
Young Adult

Substances

DLX4 protein, human
Homeodomain Proteins
Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding