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首页> 外文期刊>International Journal of Molecular Epidemiology and Genetics >Genome-wide and candidate gene association studies of placental abruption
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Genome-wide and candidate gene association studies of placental abruption

机译：胎盘早剥的全基因组和候选基因关联研究

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Placental abruption (PA), a pregnancy-related vascular disorder, is a leading cause of maternal and perinatal morbidity and mortality. The success of identifying genetic susceptibility loci for PA, a multi-factorial heritable disorder, has been limited. We conducted a genome-wide association study (GWAS) and candidate gene association study using 470 PA cases and 473 controls from Lima, Peru. Genotyping for common genetic variations (single nucleotide polymorphisms, SNPs) was conducted using the Illumina Cardio-Metabo Chip platform. Common variations in 35 genes that participate in mitochondrial biogenesis (MB) and oxidative phosphorylation (OS) were selected for the candidate gene study. Regression models were fit to examine associations of each SNP with risk of PA. In pathway analyses, we examined functions and functional relationships of genes represented by the top GWAS hits. Genetic risk scores (GRS), based on top hits of the GWAS and candidate gene analyses, respectively, were computed using the risk allele counting method. The top hit in the GWAS analyses was rs1238566 (empirical emP/em-value=1.04e-4 and FDR-adjusted emP/em-value=5.65E-04) in FLI-1 gene, a megakaryocyte-specific transcription factor. Networks of genes involved in lipid metabolism and cell signaling were significantly enriched by the 51 genes whose SNPs were among the top 200 GWAS hits (emP/em-value <2.1e-3). SNPs known to regulate MB (e.g. CAMK2B, NR1H3, PPARG, PRKCA, and THRB) and OP (e.g., COX5A, and NDUF family of genes) were associated with PA risk (emP/em-value <0.05). GRS was significantly associated with PA risk (trend emP/em-value <0.001 and 0.01 for GWAS and candidate gene based GRS, respectively). Our study suggests that integrating multiple analytical strategies in genetic association studies can provide opportunities for identifying genetic risk factors and novel molecular mechanisms that underlie PA.
机译：胎盘早剥（PA）是一种与妊娠有关的血管疾病，是孕产妇和围产儿发病和死亡的主要原因。鉴定PA的遗传易感基因座（一种多因素遗传性疾病）的成功受到限制。我们使用来自秘鲁利马的470个PA病例和473个对照进行了全基因组关联研究（GWAS）和候选基因关联研究。使用Illumina Cardio-Metabo Chip平台进行常见遗传变异（单核苷酸多态性，SNP）的基因分型。选择了参与线粒体生物发生（MB）和氧化磷酸化（OS）的35个基因的共同变异进行候选基因研究。回归模型适合检验每个SNP与PA风险的关联。在途径分析中，我们检查了由顶级GWAS命中代表的基因的功能和功能关系。使用风险等位基因计数方法分别基于GWAS的最高命中率和候选基因分析来计算遗传风险评分（GRS）。在GWAS分析中，命中率最高的是FLI-1中的rs1238566（经验 P 值= 1.04e-4和FDR调整后的 P 值= 5.65E-04）。基因，一种巨核细胞特异性转录因子。参与脂质代谢和细胞信号转导的基因网络被51个SNP位居200个GWAS命中率最高的基因显着丰富（ P 值＆＃x0003c; 2.1e-3）。已知调控MB的SNP（例如CAMK2B，NR1H3，PPARG，PRKCA和THRB）和OP（例如COX5A和NDUF基因家族）与PA风险（ P 值＆＃x0003c）相关; 0.05）。 GRS与PA风险显着相关（GWAS和基于候选基因的GRS的趋势 P -值＆＃x0003c; 0.001和0.01）。我们的研究表明，将多种分析策略整合到遗传关联研究中可以为识别遗传风险因素和PA潜在的新型分子机制提供机会。

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