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Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (5): 815-820. doi: 10.19723/j.issn.1671-167X.2020.05.004

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Evaluating the effect of WNT pathway genes considering interactions on the risk of non-syndromic oral clefts among Chinese populations

Meng-ying WANG1,Wen-yong LI1,Ren ZHOU1,Si-yue WANG1,Dong-jing LIU1,Hong-chen ZHENG1,Jing LI2,Nan LI3,Zhi-bo ZHOU3,Hong-ping ZHU3,Tao WU1,∆(),Yong-hua HU1   

  1. 1. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China
    2. Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
    3. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China
  • Received:2018-07-10 Online:2020-10-18 Published:2020-10-15
  • Contact: Tao WU E-mail:twu@bjmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(81102178);National Natural Science Foundation of China(81573225);Beijing Municipal Natural Science Foundation(7172115)

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Abstract:

Objective: In this study, we used genome-wide association study (GWAS) data to explore whether WNT pathway genes were associated with non-syndromic oral clefts (NSOC) considering gene-gene interaction and gene-environment interaction. Methods: We conducted the analysis using 806 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios and 202 non-syndromic cleft palate (NSCP) case-parent trios among Chinese populations selected from an international consortium established for a GWAS of non-syndromic oral clefts. Genotype data and maternal environmental exposures were collected through DNA samples and questionnaires. Conditional Logistic regression models were adopted to explore gene-gene interaction and gene-environment interaction using trio package in R software. The threshold of significance level was set as 3.47×10-4 using Bonferroni correction. Results: A total of 144 single nucleotide polymorphisms (SNPs) in seven genes passed the quality control process in NSCL/P trios and NSCP trios, respectively. Totally six pairs of SNPs interactions showed statistically significant SNP-SNP interaction (P<3.47×10-4) after Bonferroni correction, which were rs7618735 (WNT5A) and rs10848543 (WNT5B), rs631948 (WNT11) and rs556874 (WNT5A), and rs631948 (WNT11) and rs472631 (WNT5A) among NSCL/P trios; rs589149 (WNT11) and rs4765834 (WNT5B), rs1402704 (WNT11) and rs358792 (WNT5A), and rs1402704 (WNT11) and rs358793 (WNT5A) among NSCP trios, respectively. In addition, no significant result was found for gene-environment interaction analysis in both of the NSCL/P trios and NSCP trios. Conclusion: Though this study failed to detect significant association based on gene-environment interactions of seven WNT pathway genes and the risk of NSOC, WNT pathway genes may influence the risk of NSOC through potential gene-gene interaction.

Key words: Non-syndromic oral clefts, Genome-wide association studies, WNT signaling pathway

CLC Number: 

  • R181.33

Table 1

The distribution of NSOC trios in China"

Site Male Female Total
CL/P CP CL/P CP
Taiwan 139 29 94 50 312
Shandong 193 16 81 22 312
Hubei 132 19 55 26 232
Sichuan 75 18 37 22 152
Total 539 82 267 120 1 008

Table 2

Information of the seven genes in the WNT pathway"

Subtypes Gene Chromosome Number of SNPs
NSCL/P WNT3 17 7
WNT3A 1 8
WNT5A 3 45
WNT5B 12 28
WNT9A 1 13
WNT9B 17 9
WNT11 11 34
Total 144
NSCP WNT3 17 7
WNT3A 1 7
WNT5A 3 46
WNT5B 12 28
WNT9A 1 13
WNT9B 17 9
WNT11 11 34
Total 144

Table 3

The results of gene-gene interaction analysis"

Subtypes Gene1 SNP1 MAF1 P1 Gene2 SNP2 MAF2 P2 Pinteraction RR Empirical P
NSCL/P WNT5A rs7618735 0.153 0.250 WNT5B rs10848543 0.268 0.355 2.66×10-4 1.01 2.00×10-4
WNT11 rs631948 0.360 0.601 WNT5A rs556874 0.318 0.540 3.10×10-4 1.06 3.00×10-4
WNT11 rs631948 0.360 0.601 WNT5A rs472631 0.321 0.441 3.42×10-4 1.07 4.00×10-4
NSCP WNT11 rs589149 0.444 0.940 WNT5B rs4765834 0.306 0.153 1.08×10-4 1.19 1.00×10-4
WNT11 rs1402704 0.434 0.178 WNT5A rs358792 0.273 0.502 1.37×10-4 1.10 1.00×10-4
WNT11 rs1402704 0.434 0.178 WNT5A rs358793 0.275 0.452 1.71×10-3 1.56 1.00×10-4
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