ArticleAmerican journal of medical genetics. Part A2019
Association of low-frequency genetic variants in regulatory regions with nonsyndromic orofacial clefts.
Article in American journal of medical genetics. Part A, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Whole Genome Sequencing of Discordant Monozygotic Twins Reveals Regulatory Variants Associated With Nonsyndromic Orofacial Clefts.Human mutation · 2026Article
- Functional Annotation of De Novo Variants Found Near GWAS Loci Associated With Cleft Lip With or Without Cleft Palate.Birth defects research · 2025Article
- Rare variants analyses suggest novel cleft genes in the African population.Scientific reports · 2024Article
- Rare Variants Analyses Suggest Novel Cleft Genes in the African Population.Research square · 2024Article
- Rare variant modifier analysis identifies variants in SEC24D associated with orofacial cleft subtypes.Human genetics · 2023Article
- Rare genetic variants inmedRxiv : the preprint server for health sciences · 2023Article
- Prioritization of non-coding elements involved in non-syndromic cleft lip with/without cleft palate through genome-wide analysis ofHGG advances · 2023Article
- Testing for association with rare variants in the coding and non-coding genome: RAVA-FIRST, a new approach based on CADD deleteriousness score.PLoS genetics · 2022Article
- Integration of multimodal data in the developing tooth reveals candidate regulatory loci driving human odontogenic phenotypes.Frontiers in dental medicine · 2022Article
- Rare variant association testing in the non-coding genome.Human genetics · 2020Review
- Evidence for craniofacial enhancer variation underlying nonsyndromic cleft lip and palate.Human genetics · 2020Article
- FaceBase 3: analytical tools and FAIR resources for craniofacial and dental research.Development (Cambridge, England) · 2020Review
- Craniofacial Analysis May Indicate Co-Occurrence of Skeletal Malocclusions and Associated Risks in Development of Cleft Lip and Palate.Journal of developmental biology · 2020Article
- Regulatory Mechanisms of Soft Palate Development and Malformations.Journal of dental research · 2019Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Genome-wide scans have shown that common risk alleles for orofacial clefts (OFC) tend to be located in noncoding regulatory elements and cumulatively explain only part of the heritability of OFCs. Low-frequency variants may account for some of the "missing" heritability. Therefore, we scanned low-frequency variants located within putative craniofacial enhancers to identify novel OFC risk variants and implicate new regulatory elements in OFC pathogenesis. Analyses were performed in a multiethnic sample of 1,995 cases of cleft lip with or without cleft palate (CL/P), 221 cases with cleft palate (CP) only, and 1,576 unaffected controls. One hundred and nineteen putative craniofacial enhancers identified from ChIP-Seq studies in craniofacial tissues or cell lines contained multiple low-frequency (0.01-1%) variants, which we genotyped in participants using a custom Illumina panel. Two complementary statistical approaches, sequence kernel association test and combined multivariate and collapsing, were used to test association of the aggregated low-frequency variants across each enhancer region with CL/P and CP. We discovered a significant association between CP and a branchial arch enhancer near FOXP1 (mm60; p-value = .0002). Additionally, we observed a suggestive association between CL/P and a forebrain enhancer near FOXE1 (hs1717; p-value = .001). These findings suggest that low-frequency variants in craniofacial enhancer regions contribute to the complex etiology of nonsyndromic OFCs.
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