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
-
- Phenotype
- Alleles
- Molecular Sequence Annotation
- Genome-Wide Association Study
- Quantitative Trait Loci*
- PubMed
- 33108691 Full text @ J. Cell. Mol. Med.
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