Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
Nat Genet. 2013 Jul;45(7):822-4. doi: 10.1038/ng.2637. Epub 2013 May 26.
We carried out a genome-wide association study (GWAS) of congenital heart disease (CHD). Our discovery cohort comprised 1,995 CHD cases and 5,159 controls and included affected individuals from each of the 3 major clinical CHD categories (with septal, obstructive and cyanotic defects). When all CHD phenotypes were considered together, no region achieved genome-wide significant association. However, a region on chromosome 4p16, adjacent to the MSX1 and STX18 genes, was associated (P = 9.5 × 10⁻⁷) with the risk of ostium secundum atrial septal defect (ASD) in the discovery cohort (N = 340 cases), and this association was replicated in a further 417 ASD cases and 2,520 controls (replication P = 5.0 × 10⁻⁵; odds ratio (OR) in replication cohort = 1.40, 95% confidence interval (CI) = 1.19-1.65; combined P = 2.6 × 10⁻¹⁰). Genotype accounted for ~9% of the population-attributable risk of ASD.
我们进行了一项先天性心脏病（CHD）的全基因组关联研究（GWAS）。我们的发现队列包括 1995 例 CHD 病例和 5159 例对照，包括来自 3 种主要临床 CHD 类别（间隔缺损、阻塞性和发绀性缺损）的受影响个体。当所有 CHD 表型一起考虑时，没有区域达到全基因组显著关联。然而，在染色体 4p16 上紧邻 MSX1 和 STX18 基因的一个区域与发现队列中继发孔型房间隔缺损（ASD）的风险相关（P = 9.5×10⁻⁷）（N = 340 例），并且这种关联在另外 417 例 ASD 病例和 2520 例对照中得到了复制（复制 P = 5.0×10⁻⁵；复制队列的比值比（OR）= 1.40，95%置信区间（CI）= 1.19-1.65；合并 P = 2.6×10⁻¹⁰）。基因型占 ASD 人群归因风险的约 9%。
