Integrative Multi-omics Analysis Identifies Genetic Variants Contributing to Non-syndromic Cleft Lip with or without Cleft Palate.
Chin J Dent Res
; 27(1): 65-73, 2024 Mar 28.
Article
in En
| MEDLINE
| ID: mdl-38546521
ABSTRACT
OBJECTIVE:
To provide novel insights into the aetiology of non-syndromic cleft lip with or without cleft palate (NSCL/P) by integrating multi-omics data and exploring susceptibility genes associated with NSCL/P.METHODS:
A two-stage genome-wide association study (GWAS) of NSCL/P was performed, involving a total of 1,069 cases and 1,724 controls. Using promoter capture Hi-C (pCHi-C) datasets in human embryonic stem cells (hESC) and chromatin immunoprecipitation sequencing (ChIP-seq) in craniofacial tissues, we filtered out single nucleotide polymorphisms (SNPs) with active cis-regulation and their target genes. Additionally, we employed expression quantitative trait loci (eQTL) analysis to identify candidate genes.RESULTS:
Thirteen SNPs were identified as cis-regulation units associated with the risk of NSCL/P. Five of these were proven to be active in chromatin states in early human craniofacial development (rs7218002 odds ratio [OR] 1.50, P = 8.14E-08; rs835367 OR 0.78, P = 3.48E- 05; rs77022994 OR 0.55, P = 1.05E-04; rs961470 OR 0.73, P = 1.38E-04; rs17314727 OR 0.73, P = 1.85E-04). Additionally, pCHi-C and eQTL analysis prioritised three candidate genes (rs7218002 NTN1, rs835367 FGGY, LINC01135). NTN1 and FGGY were expressed in mouse orofacial development. Deficiencies in NTN1, FGGY and LINC01135 were associated with cleft palate and cleft lip, abnormal facial shape and bifid uvula, and abnormality of the face, respectively.CONCLUSION:
Our study identified five SNPs (rs7218002, rs835367, rs77022994, rs961470 and rs17314727) and three susceptibility genes (NTN1, FGGY and LINC01135) associated with NSCL/P. These findings contribute to a better understanding of the genetic factors involved.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cleft Lip
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Cleft Palate
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Ichthyosis, Lamellar
Limits:
Animals
/
Humans
Language:
En
Journal:
Chin J Dent Res
Journal subject:
ODONTOLOGIA
Year:
2024
Document type:
Article
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM