PUBLICATION
Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate
- Authors
- Ma, L., Lou, S., Miao, Z., Yao, S., Yu, X., Kan, S., Zhu, G., Yang, F., Zhang, C., Zhang, W., Wang, M., Wang, L., Pan, Y.
- ID
- ZDB-PUB-201028-10
- Date
- 2020
- Source
- Journal of Cellular and Molecular Medicine 24(23): 13669-13678 (Journal)
- Registered Authors
- Keywords
- association signals, molecular genetics, orofacial clefts, susceptibility, zebrafish
- MeSH Terms
-
- Alleles
- Animals
- Case-Control Studies
- Cleft Lip/diagnosis*
- Cleft Lip/genetics*
- Cleft Palate/diagnosis*
- Cleft Palate/genetics*
- Computational Biology/methods
- Disease Models, Animal
- Female
- Gene Editing
- Genetic Association Studies*/methods
- Genetic Predisposition to Disease*
- Genome-Wide Association Study
- Genotype
- Humans
- Male
- Molecular Sequence Annotation
- Odds Ratio
- Phenotype
- Polymorphism, Single Nucleotide
- Quantitative Trait Loci*
- Zebrafish
- PubMed
- 33108691 Full text @ J. Cell. Mol. Med.
Citation
Ma, L., Lou, S., Miao, Z., Yao, S., Yu, X., Kan, S., Zhu, G., Yang, F., Zhang, C., Zhang, W., Wang, M., Wang, L., Pan, Y. (2020) Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate. Journal of Cellular and Molecular Medicine. 24(23):13669-13678.
Abstract
Although several genome-wide association studies (GWAS) of non-syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in-depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case-parent trios and another in-house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3' of SERTAD4, P = 6.44 × 10-14 ; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10-13 and 2.80 × 10-11 , respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10-6 ; rs2095293: intron of NR6A1, P = 2.98 × 10-5 ). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10-16 ). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down-regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping