Genome-wide association study identifies a maternal copy-number deletion in PSG11 enriched among preeclampsia patients.
Genome-wide association study identifies a maternal copy-number deletion in PSG11 enriched among preeclampsia patients.
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DOI：
10.1186/1471-2393-12-61
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发表时间：
2012-06-29
影响因子：
3.1
通讯作者：
Dewan AT
中科院分区：
文献类型：
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作者：
Zhao L;Triche EW;Walsh KM;Bracken MB;Saftlas AF;Hoh J;Dewan AT
先兆子痫（PE）的具体遗传贡献目前尚不清楚。这项全基因组关联研究（GWAS）旨在确定与PE病因相关的母体单核苷酸多态性（SNP）和拷贝数变异（CNV）。对177例PE病例（根据国家心肺血液研究所指南诊断）和116例血压正常的对照者进行了全基因组扫描。来自爱荷华州的白色女性研究受试者在AffyssSNP 6.0微阵列上进行基因分型。使用CNVision合并使用四种检测算法（Birdseye、Canary、PennCNV和QuantiSNP）的组合进行的CNV调用，并使用严格的优先级标准进行筛选。由于有限的DNA量和拷贝数缺失的有害性质，先验地决定仅选择缺失用于使用定量实时PCR对整个病例对照数据集进行测定。前四个SNP候选者的等位基因或基因型p值在10-5和10-6之间，然而，没有一个超过Bonferroni校正的显著性阈值。选择在多个病例中检测到的符合优先级标准的三个复发性罕见缺失进行靶向基因分型。发现了一个特别感兴趣的基因座，显示19q13.31中病例缺失的富集（5/169例和1/114对照），其包括与高度可塑性基因组区域相邻的PSG 11基因。这些区域的所有算法调用均经试验确认。CNVs可能会带来PE的风险，并代表值得进一步研究的有趣区域。从GWAS中鉴定出的最佳SNP候选者，尽管不是全基因组显著的，但可能有助于为PE遗传学的未来研究提供信息。
Specific genetic contributions for preeclampsia (PE) are currently unknown. This genome-wide association study (GWAS) aims to identify maternal single nucleotide polymorphisms (SNPs) and copy-number variants (CNVs) involved in the etiology of PE. A genome-wide scan was performed on 177 PE cases (diagnosed according to National Heart, Lung and Blood Institute guidelines) and 116 normotensive controls. White female study subjects from Iowa were genotyped on Affymetrix SNP 6.0 microarrays. CNV calls made using a combination of four detection algorithms (Birdseye, Canary, PennCNV, and QuantiSNP) were merged using CNVision and screened with stringent prioritization criteria. Due to limited DNA quantities and the deleterious nature of copy-number deletions, it was decided a priori that only deletions would be selected for assay on the entire case-control dataset using quantitative real-time PCR. The top four SNP candidates had an allelic or genotypic p-value between 10-5 and 10-6, however, none surpassed the Bonferroni-corrected significance threshold. Three recurrent rare deletions meeting prioritization criteria detected in multiple cases were selected for targeted genotyping. A locus of particular interest was found showing an enrichment of case deletions in 19q13.31 (5/169 cases and 1/114 controls), which encompasses the PSG11 gene contiguous to a highly plastic genomic region. All algorithm calls for these regions were assay confirmed. CNVs may confer risk for PE and represent interesting regions that warrant further investigation. Top SNP candidates identified from the GWAS, although not genome-wide significant, may be useful to inform future studies in PE genetics.
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