Novel caries loci in children and adults implicated by genome-wide analysis of families

Abstract

BackgroundDental caries is a common chronic disease among children and adults alike, posing a substantial health burden. Caries is affected by multiple genetic and environmental factors, and prior studies have found that a substantial proportion of caries susceptibility is genetically inherited.MethodsTo identify such genetic factors, we conducted a genome-wide linkage scan in 464 extended families with 2616 individuals from Iowa, Pennsylvania and West Virginia for three dental caries phenotypes: (1) PRIM: dichotomized as zero versus one or more affected primary teeth, (2) QTOT1: age-adjusted quantitative caries measure for both primary and permanent dentitions including pre-cavitated lesions, and (3) QTOT2: age-adjusted quantitative caries excluding pre-cavitated lesions. Genotyping was conducted for approximately 600,000 SNPs on an Illumina platform, pruned to 127,511 uncorrelated SNPs for the analyses reported here.ResultsMultipoint non-parametric linkage analyses generated peak LOD scores exceeding 2.0 for eight genomic regions, but no LOD scores above 3.0 were observed. The maximum LOD score for each of the three traits was 2.90 at 1q25.3 for PRIM, 2.38 at 6q25.3 for QTOT1, and 2.76 at 5q23.3 for QTOT2. Some overlap in linkage regions was observed among the phenotypes. Genes with a potential role in dental caries in the eight chromosomal regions include CACNA1E, LAMC2, ALMS1, STAMBP, GXYLT2, SLC12A2, MEGF10, TMEM181, ARID1B, and, as well as genes in several immune gene families. Our results are also concordant with previous findings from association analyses on chromosomes 11 and 19.ConclusionsThese multipoint linkage results provide evidence in favor of novel chromosomal regions, while also supporting earlier association findings for these data. Understanding the genetic etiology of dental caries will allow designing personalized treatment plans based on an individual’s genetic risk of disease.Electronic supplementary materialThe online version of this article (10.1186/s12903-018-0559-6) contains supplementary material, which is available to authorized users.

Current State and Challenges of the Global Outcomes of Dental Caries Research in the Meta-Omics Era

“…Second, the phenotypic definitions used in this study did not depict the caries extent or severity, which might have contributed to the low statistical power of analysis (Haworth et al, 2018;Docherty et al, 2016). Govil et al, 2018 conducted the first study applying the genome-wide multipoint linkage approach to make full use of familial inheritance to explore the genetic etiology of caries. Promisingly, the linkage findings nominated genes on six chromosomes as having potential involvement in caries etiology, either directly or via an indirect contribution in human immune and host defense response, blood glucose levels, and secretory function of the salivary glands (Govil et al, 2018).…”

“…Govil et al, 2018 conducted the first study applying the genome-wide multipoint linkage approach to make full use of familial inheritance to explore the genetic etiology of caries. Promisingly, the linkage findings nominated genes on six chromosomes as having potential involvement in caries etiology, either directly or via an indirect contribution in human immune and host defense response, blood glucose levels, and secretory function of the salivary glands (Govil et al, 2018). In another approach, the Vieira group presented the first study to separate dental caries into more discrete sub-phenotypes, defined from longitudinal data, to better aid in gene identification studies.…”

Genetic and epigenetic factors of caries

“…Серед досліджуваних генів-кандидатів, потенційно асоційованих з розвитком каріозного процесу, можна категоризувати такі чотири категорії: 1) гени, що визначають розвиток і формування емалі; 2) гени, що визначають структуру та процес формування слини; 3) гени, що визначають особливості імунної відповіді; 4) гени, що впливають на метаболізм вуглеводів [1,5,7,12,15,16]. Удальцова К.О.…”

Amylase Alpha 1 Gene (<b><i>AMY1</i></b>) Copy Number Variation and Dental Caries Experience: A Pilot Study among Adults in Lithuania

“…Even though genome-wide studies on dental caries have not identified an association between the genomic region where AMY1 is located and dental caries Shaffer et al, 2013;Zeng et al, 2013;Govil et al, 2018;Orlova et al, 2019;Shungin et al, 2019], as early as 1959, Goodman et al [1959] showed that α-amylase activity is hereditary and suggested that it is related to higher dental caries experience in a twin study. However, there is a lack of studies on how individual differences in AMY1 CNV affect caries experience and whether AMY1 CNV could be used as a genetic biomarker for patients with a high caries risk.…”