Gene-gene/gene-environment interaction of transforming growth factor-β signaling pathway and the risk of non-syndromic oral clefts
10.19723/j.issn.1671-167X.2024.03.002
- VernacularTitle:转化生长因子β信号通路与非综合征型唇腭裂发病风险的基因-基因及基因-环境交互作用
- Author:
Tianjiao HOU
1
,
2
;
Zhibo ZHOU
;
Zhuqing WANG
;
Mengying WANG
;
Siyue WANG
;
Hexiang PENG
;
Huangda GUO
;
Yixin LI
;
Hanyu ZHANG
;
Xueying QIN
;
Yiqun WU
;
Hongchen ZHENG
;
Jing LI
;
Tao WU
;
Hongping ZHU
Author Information
1. 北京大学公共卫生学院流行病与卫生统计学系,北京 100191
2. 重大疾病流行病学教育部重点实验室(北京大学),北京 100191
- Keywords:
Non-syndromic cleft lip with or without cleft palate;
Transforming growth factor-β signaling pathway;
Genome-wide association study;
Case-parent trio
- From:
Journal of Peking University(Health Sciences)
2024;56(3):384-389
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the association between polymorphisms of transforming growth factor-β(TGF-β)signaling pathway and non-syndromic cleft lip with or without cleft palate(NSCL/P)among Asian populations,while considering gene-gene interaction and gene-environment interaction.Methods:A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium,which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P.After stringent quality control measures,343 single nucleotide polymorphism(SNP)spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS)dataset for further analysis.The transmission disequilibrium test(TDT)was used to test for SNP effects.The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction.Environmental factors collected for the study in-cluded smoking during pregnancy,passive smoking during pregnancy,alcohol intake during pregnancy,and vitamin use during pregnancy.Due to the low rates of exposure to smoking during pregnancy and al-cohol consumption during pregnancy(＜3％),only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed.The threshold for statistical significance was rigorously set at P=1.46 × 10-4,applying Bonferroni correction to account for multiple testing.Results:A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P(P＜0.05),but none of these associations was statistically significant after Bonferroni's multiple test correction.How-ever,there were 6 pairs of SNPs rs4939874(SMAD2)and rs1864615(TGFBR2),rs2796813(TGFB2)and rs2132298(TGFBR2),rs4147358(SMAD3)and rs1346907(TGFBR2),rs4939874(SMAD2)and rs1019855(TGFBR2),rs4939874(SMAD2)and rs12490466(TGFBR2),rs2009112(TGFB2)and rs4075748(TGFBR2)showed statistically significant SNP-SNP interaction(P＜1.46 × 10-4).In contrast,the analysis of gene-environment interactions did not yield any significant results after being cor-rected by multiple testing.Conclusion:The comprehensive evaluation of SNP associations and interac-tions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations.However,the significant gene-gene interactions identified suggest that the genetic architec-ture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling path-way.These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.
