School of Public Health, Peking University, Beijing 100191, China.
School of Stomatology, Peking University, Beijing 100081, China.
Int J Environ Res Public Health. 2019 Feb 15;16(4):557. doi: 10.3390/ijerph16040557.
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of common birth defects in China, with genetic and environmental components contributing to the etiology. Genome wide association studies (GWASs) have identified and to be associated with NSCL/P among Chinese populations. This study aimed to further explore potential genetic effect and gene-environment interaction among genes based on haplotype analysis, using 806 Chinese case-parent NSCL/P trios drawn from an international consortium which conducted a genome-wide association study. After the process of quality control, 190 single nucleotide polymorphisms (SNPs) of genes were included for analyses. Haplotype and haplotype-environment interaction analyses were conducted in Population-Based Association Test (PBAT) software. A 2-SNP haplotype and three 3-SNP haplotypes showed a significant association with the risk of NSCL/P after Bonferroni correction (corrected significance level = 2.6 × 10). Moreover, haplotype-environment interaction analysis identified these haplotypes respectively showing statistically significant interactions with maternal multivitamin supplementation or maternal environmental tobacco smoke. This study showed SPRY2 to be associated with NSCL/P among the Chinese population through not only gene effects, but also a gene-environment interaction, highlighting the importance of considering environmental exposures in the genetic etiological study of NSCL/P.
非综合征性唇裂伴或不伴腭裂（NSCL/P）是中国常见的出生缺陷之一，其病因涉及遗传和环境因素。全基因组关联研究（GWAS）已经鉴定出和与中国人群中的 NSCL/P 相关。本研究旨在通过单体型分析进一步探讨基于单体型分析的 基因之间的潜在遗传效应和基因-环境相互作用，使用来自国际联盟的 806 个中国病例-父母 NSCL/P 三核苷酸进行研究，该联盟进行了全基因组关联研究。经过质量控制过程，纳入了 基因的 190 个单核苷酸多态性（SNP）进行分析。单体型和单体型-环境相互作用分析在基于人群的关联测试（PBAT）软件中进行。经过 Bonferroni 校正（校正显著水平=2.6×10），一个 2-SNP 单体型和三个 3-SNP 单体型与 NSCL/P 的风险显著相关。此外，单体型-环境相互作用分析确定这些单体型分别与母体多种维生素补充或母体环境烟草烟雾存在统计学上显著的相互作用。本研究表明，SPRY2 不仅通过基因效应，而且通过基因-环境相互作用与中国人群中的 NSCL/P 相关，强调了在 NSCL/P 的遗传病因学研究中考虑环境暴露的重要性。
