Journal article
The intersection of the genetic architectures of orofacial clefts and normal facial variation
Frontiers in genetics, Vol.12, 626403
02/22/2021
DOI: 10.3389/fgene.2021.626403
PMCID: PMC7937973
PMID: 33692830
Abstract
Unaffected relatives of individuals with non-syndromic cleft lip with or without cleft palate (NSCL/P) show distinctive facial features. The presence of this facial endophenotype is potentially an expression of underlying genetic susceptibility to NSCL/P in the larger unselected population. To explore this hypothesis, we first partitioned the face into 63 partially overlapping regions representing global-to-local facial morphology and then defined endophenotypic traits by contrasting the 3D facial images from 264 unaffected parents of individuals with NSCL/P versus 3,171 controls. We observed distinct facial features between parents and controls across 59 global-to-local facial segments at nominal significance (p ≤ 0.05) and 52 segments at Bonferroni corrected significance (p < 1.2 × 10-3), respectively. Next, we quantified these distinct facial features as univariate traits in another dataset of 8,246 unaffected European individuals and performed a genome-wide association study. We identified 29 independent genetic loci that were associated (p < 5 × 10-8) with at least one of the tested endophenotypic traits, and nine genetic loci also passed the study-wide threshold (p < 8.47 × 10-10). Of the 29 loci, 22 were in proximity of loci previously associated with normal facial variation, 18 were near genes that show strong evidence in orofacial clefting (OFC), and another 10 showed some evidence in OFC. Additionally, polygenic risk scores for NSCL/P showed associations with the endophenotypic traits. This study thus supports the hypothesis of a shared genetic architecture of normal facial development and OFC.
status: published
Details
- Title: Subtitle
- The intersection of the genetic architectures of orofacial clefts and normal facial variation
- Creators
- Karlijne Indencleef - KU LeuvenHanne Hoskens - KU LeuvenMyoung Keun Lee - University of PittsburghJulie D White - Pennsylvania State UniversityChenxing Liu - University of PittsburghRyan J Eller - Indiana University – Purdue University IndianapolisSahin Naqvi - Stanford UniversityGeorge L Wehby - University of IowaLina M Moreno Uribe - University of IowaJacqueline T Hecht - Department of Pediatrics, McGovern Medical School and School of Dentistry, UT Health at Houston, Houston, TX, United States.Ross E Long JrKaare Christensen - University of Southern DenmarkFrederic W Deleyiannis - University of Colorado Colorado SpringsSusan Walsh - Indiana University – Purdue University IndianapolisMark D Shriver - Pennsylvania State UniversityStephen Richmond - Cardiff UniversityJoanna Wysocka - Stanford UniversityHilde Peeters - KU LeuvenJohn R Shaffer - University of PittsburghMary L Marazita - University of PittsburghGreet Hens - KU LeuvenSeth M Weinberg - University of PittsburghPeter Claes - KU Leuven
- Resource Type
- Journal article
- Publication Details
- Frontiers in genetics, Vol.12, 626403
- DOI
- 10.3389/fgene.2021.626403
- PMID
- 33692830
- PMCID
- PMC7937973
- NLM abbreviation
- Front Genet
- ISSN
- 1664-8021
- Publisher
- Frontiers Media
- Language
- English
- Date published
- 02/22/2021
- Academic Unit
- Preventive and Community Dentistry; Orthodontics; Health Management and Policy; Economics; Craniofacial Anomalies Research Center; Public Policy Center (Archive)
- Record Identifier
- 9984229996702771
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