Open AccessIdentification of novel susceptibility loci for non‐syndromic cleft lip with or without cleft palate
Author(s) -
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
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15878
Subject(s) - genome wide association study , single nucleotide polymorphism , genetics , medicine , cohort , intron , genetic association , biology , han chinese , etiology , bioinformatics , genotype , gene
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.