Study regarding the parent-of-origin effect of WNT pathway genes on non-syndromic cleft lip with or without cleft palate among the Chinese population

Siyue Wang; Mengying Wang; Wenyong LI; Ren Zhou; Hongchen Zheng; Dongjing Liu; Nan LI; Zhibo Zhou; Hongping Zhu; Tao WU

Return

Study regarding the parent-of-origin effect of WNT pathway genes on non-syndromic cleft lip with or without cleft palate among the Chinese population

VernacularTitle: 中国人群WNT代谢通路与非综合征型唇腭裂的亲源效应分析
Author: Siyue WANG ¹ ; Mengying WANG ¹ ; Wenyong LI ¹ ; Ren ZHOU ¹ ; Hongchen ZHENG ¹ ; Dongjing LIU ¹ ; Nan LI ² ; Zhibo ZHOU ² ; Hongping ZHU ² ; Tao WU ¹
Author Information

1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
2. Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University, Beijing 100081, China
Publication Type:Journal Article
Keywords: Non-syndromic oral clefts; Parent of origin; Association study; Case-parent trio; WNT pathway genes
From:Chinese Journal of Epidemiology 2019;40(6):670-675
CountryChina
Language:Chinese
Abstract: Objective:Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with its genetic evidence widely explored. This study explored the potential the parent-of-origin (PoO) effect of WNT pathway on the risks of NSCL/P, using a case-parent trio design.
Methods:Data on the single nucleotide polymorphism (SNP) of WNT genes were selected from a genome-wide association study (GWAS). A total of 806 Chinese non-syndromic cleft lip patients, with or without cleft palate (NSCL/P) case-parent trios, were gathered from an international consortium. PoO effect of WNT pathway genes and its haplotypes were explored by log-linear models. Additional Wald tests were performed to assess: a) the heterogeneity of PoO effect between different maternal exposures, b) the interaction between PoO effect, c) maternal exposure to environmental tobacco smoke (ETS), and d) multivitamin supplementation during pregnancy. The threshold for statistical significance was adjusted as 3.47×10^-4, according to Bonferroni correction.
Results:After quality control, a total of 144 SNPs within seven genes were included for analyses, among which 8 SNPs were of potential PoO effect (P<0.05). However, none of them achieved the statistical significance after Bonferroni correction. The haplotype rs4074668-rs12725747 (T-A) on WNT9A showed significant PoO effect, based on the haplotype test for PoO (P=2.74×10^-4). In addition, no statistically significant interaction was found in further exploration of this haplotype under environmental exposures as ETS or multivitamin supplementation.
Conclusions:Genes in the WNT pathway may influence the NSCL/P risks through the potential PoO effect. Particularly, the haplotype rs4074668-rs12725747 (T-A) on WNT9A presented significant PoO effect on NSCL/P, statistically. From this current study, findings on WNT pathway related risks among the NSCL/P, need to be further validated by independent samples in the future.