Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate.
J Cell Mol Med
; 24(23): 13669-13678, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-33108691
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenda Labial
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Fissura Palatina
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Predisposição Genética para Doença
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Locos de Características Quantitativas
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Estudos de Associação Genética
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China