Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Morrison J

PROVIDER: S-EPMC4743689 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Morrison Jean J Laurie Cathy C CC Marazita Mary L ML Sanders Anne E AE Offenbacher Steven S Salazar Christian R CR Conomos Matthew P MP Thornton Timothy T Jain Deepti D Laurie Cecelia A CA Kerr Kathleen F KF Papanicolaou George G Taylor Kent K Kaste Linda M LM Beck James D JD Shaffer John R JR

Human molecular genetics 20151211 4

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 ...[more]

PMID: 26662797

Similar Datasets

Project description:Introduction:Genetic variants associated with nicotine dependence have previously been identified, primarily in European-ancestry populations. No genome-wide association studies (GWAS) have been reported for smoking behaviors in Hispanics/Latinos in the United States and Latin America, who are of mixed ancestry with European, African, and American Indigenous components. Methods:We examined genetic associations with smoking behaviors in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (N = 12 741 with smoking data, 5119 ever-smokers), using ~2.3 million genotyped variants imputed to the 1000 Genomes Project phase 3. Mixed logistic regression models accounted for population structure, sampling, relatedness, sex, and age. Results:The known region of CHRNA5, which encodes the ?5 cholinergic nicotinic receptor subunit, was associated with heavy smoking at genome-wide significance (p ? 5 × 10-8) in a comparison of 1929 ever-smokers reporting cigarettes per day (CPD) > 10 versus 3156 reporting CPD ? 10. The functional variant rs16969968 in CHRNA5 had a p value of 2.20 × 10-7 and odds ratio (OR) of 1.32 for the minor allele (A); its minor allele frequency was 0.22 overall and similar across Hispanic/Latino background groups (Central American = 0.17; South American = 0.19; Mexican = 0.18; Puerto Rican = 0.22; Cuban = 0.29; Dominican = 0.19). CHRNA4 on chromosome 20 attained p < 10-4, supporting prior findings in non-Hispanics. For nondaily smoking, which is prevalent in Hispanic/Latino smokers, compared to daily smoking, loci on chromosomes 2 and 4 achieved genome-wide significance; replication attempts were limited by small Hispanic/Latino sample sizes. Conclusions:Associations of nicotinic receptor gene variants with smoking, first reported in non-Hispanic European-ancestry populations, generalized to Hispanics/Latinos despite different patterns of smoking behavior. Implications:We conducted the first large-scale genome-wide association study (GWAS) of smoking behavior in a US Hispanic/Latino cohort, and the first GWAS of daily/nondaily smoking in any population. Results show that the region of the nicotinic receptor subunit gene CHRNA5, which in non-Hispanic European-ancestry smokers has been associated with heavy smoking as well as cessation and treatment efficacy, is also significantly associated with heavy smoking in this Hispanic/Latino cohort. The results are an important addition to understanding the impact of genetic variants in understudied Hispanic/Latino smokers.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets