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Genome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL).

TitleGenome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL).
Publication TypePublication
AuthorsMorrison J, Laurie CC, Marazita ML, Sanders AE, Offenbacher S, Salazar CR, Conomos MP, Thornton T, Jain D, Laurie CA, Kerr KF, Papanicolaou G, Taylor K, Kaste LM, Beck JD, Shaffer JR
JournalHum Mol Genet
Date Published2016 Feb 15
KeywordsAdult, Aged, Community Health Centers, Dental Caries, Female, Genetic Predisposition to Disease, genome-wide association study, Hispanic or Latino, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18-74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20-53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10(-10)), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10(-8)) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata.

Alternate JournalHum Mol Genet
PubMed ID26662797
PubMed Central IDPMC4743689
Grant ListP01 GM099568 / GM / NIGMS NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
K01 CA148958 / CA / NCI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
T32 GM081062 / GM / NIGMS NIH HHS / United States
WT098017 / WT_ / Wellcome Trust / United Kingdom
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
Manuscript Status: