Dental Caries: Whole Genome Association and Gene x Environment Studies

描述（由申请人提供）：龋齿（也称为蛀牙）仍然是儿童最常见的慢性疾病。虽然在过去的40年里，龋齿的总体患病率有所下降，但是在过去的12年里，2-11岁儿童的初级牙列龋齿和平均龋齿率显著增加。儿童龋齿是一个严重的公共卫生问题，因为它带来了相关的健康问题，而且口腔健康方面的差异导致贫困儿童和得不到充分服务的种族和族裔群体的平均患病率高得多。这些问题引起了人们的关注，2005年，美国儿科学会将儿童口腔健康作为他们最关注的领域之一，就像大多数NIDCR“差异中心”一样。一个人患龋齿的风险有多种因素，包括环境因素，如饮食、口腔卫生、氟化物暴露和致龋齿细菌的定植水平，以及宿主因素，如唾液流。无论他们所接触的环境风险因素如何，仍然有一些人似乎更容易患龋齿，有些人对龋齿具有极强的抵抗力，这意味着遗传因素在龋齿病因学中也起着重要作用。这一结论得到了对人类和动物的研究的支持，最令人信服的证据来自对分开抚养的双胞胎的研究，研究人员发现，在单卵双胞胎（MZ）中，牙齿和表面恢复或龋齿的比例有显著的相似性，而在异卵双胞胎（DZ）中则没有，并估计遗传对龋齿的贡献为40%。尽管有强有力的证据表明遗传因素与龋齿风险有关，但对龋齿候选基因的研究很少，也没有公布全基因组扫描结果。因此，本研究的目标是通过多个美国站点确定的家庭和个人中的大量snp（500,000或更多），对龋齿进行全基因组关联（GWA）研究。将对来自三个地点（匹兹堡大学、爱荷华大学和华盛顿大学）的样品进行初始GWA扫描，并在其他合作地点（密歇根大学和加州大学旧金山分校）进行后续研究。这项研究的成功完成将使人们更好地了解龋齿的生物学，并将导致早期识别有龋齿风险的儿童，从而允许改进和有针对性的干预措施。

DESCRIPTION (provided by applicant): Dental caries (also known as tooth decay) remains the most common chronic disease of childhood. Although overall caries prevalence has declined over the last 40 years, dental caries in the primary dentition and mean caries rates in children ages 2-11 has increased markedly over the past 12 years. Childhood caries is a serious public health issue because of associated health problems and because disparities in oral health have led to substantially higher average disease prevalence among children in poverty and in underserved racial and ethnic groups. These issues are of such concern that in 2005, the American Academy of Pediatrics made children's oral health one of their top areas of focus, as it is for the majority of the NIDCR "Disparities Centers." Multiple factors contribute to a person's risk for caries, including environmental factors such as diet, oral hygiene, fluoride exposure and the level of colonization of cariogenic bacteria and host factors such as salivary flow. There are still individuals who appear to be more susceptible to caries and those that are extremely resistant, regardless of the environmental risk factors to which they are exposed, implying that genetic factors also play an important role in caries etiology. This conclusion is supported by studies in both humans and animals, with the most compelling evidence coming from studies of twins reared apart in which investigators found significant resemblance within monozygotic (MZ) but not dizygotic (DZ) twin pairs for percentage of teeth and surfaces restored or carious and estimated the genetic contribution to caries as 40%. Despite the strong evidence of a genetic component to risk for dental caries, there have been only a few studies of candidate genes in caries, and no published genome-wide scans. Therefore, the goal of this study is to perform genome-wide association (GWA) studies of dental caries with a large panel of SNPs (500,000 or more) in families and individuals ascertained through multiple US sites. There will be an initial GWA scan in samples from three sites (University of Pittsburgh, University of Iowa, and University of Washington), with follow-up studies in additional collaborating sites (University of Michigan and UCSF). Successful completion of this study will allow a better understanding of the biology of dental caries, and will lead to earlier identification of children at risk for dental caries, thereby allowing improved and targeted interventions.