Variants on chromosome 4q21 near PKD2 and SIBLINGs are associated with dental caries

Scott Eckert; Eleanor Feingold; Margaret Cooper; Michael M Vanyukov; Brion S Maher; Rebecca L Slayton; Marcia C Willing; Steven E Reis; Daniel W McNeil; Richard J Crout; Robert J Weyant; Steven M Levy; Alexandre R Vieira; Mary L Marazita; John R Shaffer

doi:10.1038/jhg.2016.161

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Variants on chromosome 4q21 near PKD2 and SIBLINGs are associated with dental caries

Journal article

Peer reviewed

Variants on chromosome 4q21 near PKD2 and SIBLINGs are associated with dental caries

Scott Eckert, Eleanor Feingold, Margaret Cooper, Michael M Vanyukov, Brion S Maher, Rebecca L Slayton, Marcia C Willing, Steven E Reis, Daniel W McNeil, Richard J Crout, …

Journal of human genetics, Vol.62(4), pp.491-496

04/2017

DOI: 10.1038/jhg.2016.161

PMCID: PMC5367940

PMID: 28100911

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Abstract

A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family. In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089). Participants were assessed for dental caries via intraoral examination and 49 tag-SNPs were genotyped capturing much of the variation in the 4q21 locus. Linear models were used to test for genetic association, while adjusting for sex, age and components of ancestry. SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003). Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect. In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002). Our results show evidence of regional replication, though no single variant clearly accounted for the original GWAS signal. Therefore, while we interpret our results as strengthening the hypothesis that chromosome 4q21 may impact dental caries, additional work is needed.

European Continental Ancestry Group - genetics

Genetic Predisposition to Disease

Protein Kinases - genetics

Genetic Association Studies

Humans

Middle Aged

African Americans - genetics

Genotype

Male

Chromosome Mapping

Chromosomes, Human, Pair 4 - genetics

Dental Caries - genetics

ATP Binding Cassette Transporter, Sub-Family G, Member 2 - genetics

Dental Caries - pathology

Adult

Female

Polymorphism, Single Nucleotide

Neoplasm Proteins - genetics

Details

Title: Subtitle: Variants on chromosome 4q21 near PKD2 and SIBLINGs are associated with dental caries
Creators: Scott Eckert - Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Eleanor Feingold - Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
Margaret Cooper - Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Michael M Vanyukov - Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Brion S Maher - Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Rebecca L Slayton - Department of Pediatric Dentistry, School of Dentistry, University of Washington, Seattle, WA, USA
Marcia C Willing - Division of Genetics and Genomics, Department of Pediatrics, School of Medicine, Washington University at St Louis, St Louis, MO, USA
Steven E Reis - Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Daniel W McNeil - Department of Psychology, West Virginia University, Morgantown, WV, USA
Richard J Crout - Department of Periodontics, School of Dentistry, West Virginia University, Morgantown, WV, USA
Robert J Weyant - Department of Dental Public Health and Information Management, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Steven M Levy - Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA
Alexandre R Vieira - Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Mary L Marazita - Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
John R Shaffer - Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
Resource Type: Journal article
Publication Details: Journal of human genetics, Vol.62(4), pp.491-496
DOI: 10.1038/jhg.2016.161
PMID: 28100911
PMCID: PMC5367940
NLM abbreviation: J Hum Genet
ISSN: 1435-232X
eISSN: 1435-232X
Publisher: England
Grant note: R01 DE014899 / NIDCR NIH HHS R03 DE024264 / NIDCR NIH HHS U01 DE018903 / NIDCR NIH HHS R01 DE009551 / NIDCR NIH HHS R01 DE018914 / NIDCR NIH HHS R01 DE012101 / NIDCR NIH HHS R56 DE012101 / NIDCR NIH HHS R01 DA019157 / NIDA NIH HHS P50 DA005605 / NIDA NIH HHS
Language: English
Date published: 04/2017
Academic Unit: Preventive and Community Dentistry; Epidemiology; Pediatric Dentistry
Record Identifier: 9983917788502771

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