Dataset Information

Systems genetics of nonsyndromic orofacial clefting provides insights into its complex aetiology.

ABSTRACT: Nonsyndromic oral clefting (NSOC) is although one of the most common congenital disorders worldwide, its underlying molecular basis remains elusive. This process has been hindered by the overwhelmingly high level of heterogeneity observed. Given that hitherto multiple loci and genes have been associated with NSOC, and that complex diseases are usually polygenic and show a considerable level of missing heritability, we used a systems genetics approach to reconstruct the NSOC network by integrating human-based physical and regulatory interactome with whole-transcriptome microarray data. We show that the network component contains 53% (23/43) of the curated NSOC-implicated gene set and displays a highly significant propinquity (P?

SUBMITTER: Razaghi-Moghadam Z

PROVIDER: S-EPMC6336842 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Systems genetics of nonsyndromic orofacial clefting provides insights into its complex aetiology.

Razaghi-Moghadam Zahra Z Namipashaki Atefeh A Farahmand Saman S Ansari-Pour Naser N

European journal of human genetics : EJHG 20180925 2

Nonsyndromic oral clefting (NSOC) is although one of the most common congenital disorders worldwide, its underlying molecular basis remains elusive. This process has been hindered by the overwhelmingly high level of heterogeneity observed. Given that hitherto multiple loci and genes have been associated with NSOC, and that complex diseases are usually polygenic and show a considerable level of missing heritability, we used a systems genetics approach to reconstruct the NSOC network by integratin ...[more]

PMID: 30254216

Similar Datasets

Project description:Although children with oral clefts have a higher risk for dental anomalies when compared with the general population, prior studies have shown conflicting results regarding their dental decay risk. Also, few studies have assessed dental decay risk in unaffected relatives of children with clefts. Thus, the question of increased risk of dental decay in individuals with oral clefts or their unaffected relatives is still open for empirical investigation. This study characterizes dental decay in the largest international cohort to date of children with nonsyndromic clefts and their relatives, as compared with controls, and it addresses whether families with oral clefts have a significantly increased risk for dental decay versus the general population. A total of 3,326 subjects were included: 639 case probands, 1,549 unaffected relatives, and 1,138 controls. Decay was identified from in-person dental examinations or intraoral photographs. Case-control differences were tested with regression analysis. No significant differences were shown in percentage decayed and filled teeth and decayed teeth in the primary dentition (dft, dt) and permanent dentition (DFT, DT) in cases versus controls. In the cleft region, no significant differences were seen in primary or permanent decay (dt, DT) when compared with controls. No difference was found with regard to cleft type and percentage dft, dt, DFT, and DT in case probands. Nonsignificant differences were found in unaffected siblings and parents versus controls (primary and permanent dentitions). Collectively, these findings indicate that individuals with nonsyndromic oral clefts and their families do not have a higher dental decay risk as compared with the general population. These results suggest that either genetic or environmental factors underlying a higher susceptibility for dental anomalies do not increase caries risk or that the seemingly higher risk for dental decay associated with increased dental anomalies in case probands may be superseded by possible greater access to dental care.

Project description:Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ(2) statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10(-8)) and permanent dentitions (51% vs. 8%, P = 4 × 10(-62)) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the cleft and surgical interventions.

Dataset Information

Systems genetics of nonsyndromic orofacial clefting provides insights into its complex aetiology.

Publications

Systems genetics of nonsyndromic orofacial clefting provides insights into its complex aetiology.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets