| http://purl.uniprot.org/citations/35147171 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35147171 | http://www.w3.org/2000/01/rdf-schema#comment | "Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common, severe craniofacial malformation that imposes significant medical, psychosocial and financial burdens. NSCL/P is a multifactorial disorder with genetic and environmental factors playing etiologic roles. Currently, only 25% of the genetic variation underlying NSCL/P has been identified by linkage, candidate gene and genome-wide association studies. In this study, whole-genome sequencing and genome-wide genotyping followed by polygenic risk score (PRS) and linkage analyses were used to identify the genetic etiology of NSCL/P in a large three-generation family. We identified a rare missense variant in PDGFRA (c.C2740T; p.R914W) as potentially etiologic in a gene-based association test using pVAAST (P = 1.78 × 10-4) and showed decreased penetrance. PRS analysis suggested that variant penetrance was likely modified by common NSCL/P risk variants, with lower scores found among unaffected carriers. Linkage analysis provided additional support for PRS-modified penetrance, with a 7.4-fold increase in likelihood after conditioning on PRS. Functional characterization experiments showed that the putatively causal variant was null for signaling activity in vitro; further, perturbation of pdgfra in zebrafish embryos resulted in unilateral orofacial clefting. Our findings show that a rare PDGFRA variant, modified by additional common NSCL/P risk variants, have a profound effect on NSCL/P risk. These data provide compelling evidence for multifactorial inheritance long postulated to underlie NSCL/P and may explain some unusual familial patterns."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddac037"xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Yu Y."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Hecht J.T."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Huff C.D."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Below J.E."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Ruiz O.E."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Kiss D.L."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Tandon B."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Letra A."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Petty L.E."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Eisenhoffer G.T."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Alvarado R."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Shaw D.M."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Bejar N."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/author | "Bohlender R.J."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/pages | "2348-2357"xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/title | "Polygenic risk impacts PDGFRA mutation penetrance in non-syndromic cleft lip and palate."xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://purl.uniprot.org/core/volume | "31"xsd:string |
| http://purl.uniprot.org/citations/35147171 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35147171 |
| http://purl.uniprot.org/citations/35147171 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35147171 |
| http://purl.uniprot.org/uniprot/#_Q9DE49-mappedCitation-35147171 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35147171 |