Abstract：
Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies, with atrial septal defect (ASD) and ventricular septal defect (VSD) being the most common forms of simple CHD, which involve a large number of susceptibility genes. However, despite extensive research, the etiology of ASD and VSD remains unclear. Yunnan Province has advantages in exploring CHD pathogenesis due to its unique genetic background. Therefore, we aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of genes and susceptibility to simple CHD in a specific population by means of a case-control study. A total of 337 healthy controls and 767 patients with simple CHD (501 ASD and 266 VSD) from China were recruited. Candidate SNPs were identified through whole-genome sequencing of pooled CHD patients and controls (pool-seq). Genotyping from 1,104 samples was performed, and stratified analysis was conducted to explore the association between positive SNPs and CHD subtypes. χ2 tests and logistic regression were used to analyze the relationship between each SNP and simple CHD. Of 11 SNPs identified, SOD2 rs62437333 (P = 0.005) and POU5F1 rs3130504 (P = 0.017) showed differences between the control and ASD cohorts. In the dominant inheritance model hypothesis, rs62437333 allele C carriers had increased ASD (odds ratio (OR) = 2.04, P = 0.005) and combined simple CHD risk (OR = 2.33, P = 0.012) compared to DD genotype, while rs3130504 allele C carriers had increased ASD risk (OR = 1.121, P = 0.045) compared to DD genotype.
摘要：
先天性心脏病（CHD）占所有主要先天性异常的近三分之一，房间隔缺损（ASD）和室间隔缺损（VSD）是最常见的单纯性CHD，其中涉及大量的易感基因。然而,尽管进行了广泛的研究，ASD和VSD的病因尚不清楚.云南省因其独特的遗传背景,在探索CHD发病机制方面具有优势。因此,我们旨在通过病例对照研究评估特定人群中基因单核苷酸多态性(SNPs)与单纯性CHD易感性之间的关联.共纳入来自中国的337名健康对照和767名单纯性CHD患者(501名ASD和266名VSD)。通过汇集的CHD患者和对照的全基因组测序鉴定候选SNP(pool-seq)。从1,104个样本进行基因分型，并进行分层分析以探讨阳性SNP与CHD亚型之间的关联。采用χ2检验和logistic回归分析各SNP与单纯冠心病的关系。在确定的11个SNP中，SOD2rs62437333（P=0.005）和POU5F1rs3130504（P=0.017）显示对照组和ASD队列之间的差异。在显性继承模型假设中，rs62437333等位基因C携带者与DD基因型相比，ASD（比值比（OR）=2.04，P=0.005）和合并简单CHD风险（OR=2.33，P=0.012）增加，与DD基因型相比，rs3130504等位基因C携带者的ASD风险增加（OR=1.121，P=0.045）。
