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.
Highlights
Dental caries is a common chronic disease among children and adults alike, posing a substantial health burden
Subjects with primary or mixed dentition included in the primary dentition (PRIM) non-parametric linkage (NPL) analysis ranged from 15 months to 22.5 years of age, with a mean of 7.4 years
The distribution of the raw caries index by decade, age-adjusted index by decade, and age-adjusted caries index within all phenotyped individuals compared to those between 2 and 60 years of age are shown for QTOT1 and QTOT2
Summary
Dental 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. Dental caries is one of the most common chronic diseases among children and adults alike. Childhood caries is associated with failure to thrive, and it can affect self-esteem and school performance [1]. For both children and adults, caries is associated with pain and loss of teeth, and caries. There have been numerous studies investigating association of dental caries with candidate genes or with whole-genome Single Nucleotide Polymorphism (SNP) panels [8, 9]. This study found suggestive linkage of low caries experience to chromosome regions 5q13.3, 14q11.2, and 13q27.1, and high caries experience to 13q31.1 and 14q24.3 results of previous studies have, in general, not been extensively replicated, possibly due to relatively small sample sizes [8, 9] and the enumeration of genetic factors is far from complete
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