Abstract：
Congenital heart disease (CHD) is the most frequently occurring birth defect. Majority of the earlier reviews focussed on the association of genetic factors with CHD. A few epidemiological studies provide convincing evidence for environmental factors in the causation of CHD. Although the multifactorial theory of gene-environment interaction is the prevailing explanation, explicit understanding of the biological mechanism(s) involved, remains obscure. Nonetheless, integration of all the information into one platform would enable us to better understand the collective risk implicated in CHD development.
Great strides in novel genomic technologies namely, massive parallel sequencing, whole exome sequencing, multiomics studies supported by system-biology have greatly improved our understanding of the aetiology of CHD. Molecular genetic studies reveal that cardiac specific gene variants in transcription factors or signalling molecules, or structural proteins could cause CHD. Additionally, non-hereditary contributors such as exposure to teratogens, maternal nutrition, parental age and lifestyle factors also contribute to induce CHD. Moreover, DNA methylation and non-coding RNA are also correlated with CHD. Here, we inform that a complex combination of genetic, environmental and epigenetic factors interact to interfere with morphogenetic processes of cardiac development leading to CHD. It is important, not only to identify individual genetic and non-inherited risk factors but also to recognize which factors interact mutually, causing cardiac defects.
Great strides in novel genomic technologies namely, massive parallel sequencing, whole exome sequencing, multiomics studies supported by system-biology have greatly improved our understanding of the aetiology of CHD. Molecular genetic studies reveal that cardiac specific gene variants in transcription factors or signalling molecules, or structural proteins could cause CHD. Additionally, non-hereditary contributors such as exposure to teratogens, maternal nutrition, parental age and lifestyle factors also contribute to induce CHD. Moreover, DNA methylation and non-coding RNA are also correlated with CHD. Here, we inform that a complex combination of genetic, environmental and epigenetic factors interact to interfere with morphogenetic processes of cardiac development leading to CHD. It is important, not only to identify individual genetic and non-inherited risk factors but also to recognize which factors interact mutually, causing cardiac defects.
摘要：
目的：先天性心脏病（CHD）是最常见的出生缺陷。大多数早期综述集中在遗传因素与CHD的关系上。一些流行病学研究为环境因素在CHD的病因中提供了令人信服的证据。尽管基因-环境相互作用的多因素理论是普遍的解释，明确了解所涉及的生物学机制，仍然晦涩难懂。尽管如此，将所有信息整合到一个平台中，将使我们能够更好地了解CHD发展中涉及的集体风险。
结果：新型基因组技术取得了长足的进步，即大规模平行测序，整个外显子组测序，由系统生物学支持的多组学研究极大地改善了我们对CHD病因的认识.分子遗传学研究表明，转录因子或信号分子中的心脏特异性基因变异，或结构蛋白可能导致冠心病。此外,非遗传因素，如暴露于致畸剂，产妇营养,父母年龄和生活方式因素也有助于诱发冠心病。此外，DNA甲基化和非编码RNA也与CHD相关。这里,我们告知复杂的遗传组合，环境因素和表观遗传因素相互作用，干扰心脏发育的形态发生过程，导致冠心病。这很重要,不仅要识别个体遗传和非遗传危险因素，还要识别哪些因素相互作用，导致心脏缺陷.
结果：新型基因组技术取得了长足的进步，即大规模平行测序，整个外显子组测序，由系统生物学支持的多组学研究极大地改善了我们对CHD病因的认识.分子遗传学研究表明，转录因子或信号分子中的心脏特异性基因变异，或结构蛋白可能导致冠心病。此外,非遗传因素，如暴露于致畸剂，产妇营养,父母年龄和生活方式因素也有助于诱发冠心病。此外，DNA甲基化和非编码RNA也与CHD相关。这里,我们告知复杂的遗传组合，环境因素和表观遗传因素相互作用，干扰心脏发育的形态发生过程，导致冠心病。这很重要,不仅要识别个体遗传和非遗传危险因素，还要识别哪些因素相互作用，导致心脏缺陷.
