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Candidate genes and replication studies of dental caries

Lewis, Deyana (2016) Candidate genes and replication studies of dental caries. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Motivation: Dental caries (cavities) constitutes as a significant public health problem that begins in early childhood and that is steadily increasing in the US. It remains the most common chronic childhood disease, five times more common than asthma and four times more common than childhood obesity. Untreated caries disproportionately affects low socioeconomic populations and some racial/ethnic minority groups. Furthermore, dental caries is a multifactorial disease that involves many interacting variables to promote its development. Unlike other diseases, dental caries is highly preventable. However, there are still some individuals who seem to be more susceptible to caries, and those who appear to be extremely resistant, thus implying a genetic component. Therefore, we investigated a subset of genes that have some biologically plausible role in oral health for evidence of association with dental caries experience in 13 race- and age-stratified samples from six independent studies (n =3600).
Methods: Participants were genotyped for a custom panel of single nucleotide polymorphisms (SNPs) using the Illumina Golden Gate platform by the Center for Inherited Disease Research (CIDR). We tested association of these genes with dental caries in 13 race- and age-stratified samples from six independent studies of whites and blacks adults and children. We performed analyses independently for each cohort and synthesized results by meta-analysis across five childhood cohorts and across eight adult cohorts.
Results: Linear regression used to detect genetic association for a selection of candidate ion channel genes revealed two SNPs in CACNA2D1 were significantly associated with dental caries via meta-analysis across the five childhood cohorts, and in one individual childhood cohort (p < 7.1 x 10-4). In adults, genetic association was observed in three individual cohorts for potassium channel genes KCNH1 and KCNK5 (p-values<0.001). Significant associations for variants in CNIH, BCOR and IFT88 corroborate the findings of caries GWAS (Genome-Wide-Association Studies) hits from published papers in the permanent dentition. This research demonstrates the importance of genes in the etiology of dental caries which is of public health relevance. Understanding genetic determinants of dental caries could lead to new strategies to reduce caries risk and improve oral health.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lewis, Deyanaddl8@pitt.eduDDL8
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFeingold, Eleanorfeingold@pitt.eduFEINGOLD
Committee MemberMarazita, Mary Lmarazita@pitt.eduMARAZITA
Committee MemberKammerer, Candace Mcmk3@pitt.eduCMK3
Committee MemberShaffer, John Rjrs51@pitt.eduJRS51
Date: 27 January 2016
Date Type: Publication
Defense Date: 19 August 2015
Approval Date: 27 January 2016
Submission Date: 8 September 2015
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 110
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Genetics, Caries, Replication, Candidate Genes
Date Deposited: 27 Jan 2016 22:03
Last Modified: 01 Jan 2018 06:15
URI: http://d-scholarship.pitt.edu/id/eprint/26110

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