PAS Pedigrees: Identification of novel genetic variants contributing to cardiovascular disease in pedigrees with premature atherosclerosis.

The heritability of CVD has been estimated to be between 40 and 55%. Due to the low MAF, PAS-causing mutations cannot be identified by indirect genotyping because their presence cannot be inferred from common haplotypes, as has been done successfully to uncover common risk variants by GWAS. It has been shown by Ng et al that the causative gene for rare syndromes can be unequivocally identified by sequencing the exomes of only four cases and eight controls. We expect exome sequencing to result in a high number of mutations and non-causitive coding variants.EGA study EGAS00001000052

心血管疾病（CVD）的遗传力估计介于40%至55%之间。由于次要等位基因频率（Minor Allele Frequency, MAF）较低，致肺动脉狭窄（Pulmonary Artery Stenosis, PAS）的突变无法通过间接基因分型技术鉴定，原因在于无法从常见单倍型中推断此类突变的存在——而全基因组关联研究（Genome-Wide Association Study, GWAS）正是通过该策略成功发掘了常见心血管疾病的风险变异。Ng等人的研究已证实，仅对4例病例与8例对照的外显子组进行测序，即可明确鉴定出罕见综合征的致病基因。我们预期外显子组测序将检出大量突变及非致病编码变异。本研究为欧洲基因组-表型组档案馆（European Genome-phenome Archive, EGA）收录的研究EGAS00001000052。