Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate.

Content Provider	Europe PMC
Author	Ma, Lan Lou, Shu Miao, Ziyue Yao, Siyue Yu, Xin Kan, Shiyi Zhu, Guirong Yang, Fan Zhang, Chi Zhang, Weibing Wang, Meilin Wang, Lin Pan, Yongchu
Abstract	AbstractAlthough 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.
Page Count	10
ISSN	15821838
Journal	Journal of Cellular and Molecular Medicine
Volume Number	24
PubMed Central reference number	PMC7754035
Issue Number	23
PubMed reference number	33108691
e-ISSN	15824934
DOI	10.1111/jcmm.15878
Language	English
Publisher	John Wiley and Sons Inc.
Publisher Date	2020-10-27
Publisher Place	Hoboken
Access Restriction	Open
Rights License	This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Subject Keyword	association signals molecular genetics orofacial clefts susceptibility zebrafish
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Medicine