Abstract：
UNASSIGNED: Preeclampsia (PE) mainly occurs in pregnant women and is hereditary. Several genome-wide association studies (GWAS) on Caucasian samples have reported some gene loci that are associated with preeclampsia. However, these studies have not reached consistent conclusions. No previous GWAS has examined preeclampsia in the Chinese Han population.
UNASSIGNED: This study aimed to identify common genetic variations associated with preeclampsia in the Chinese Han population through two-stage case‒control studies. The discovery cohort included 92 patients with severe preeclampsia and 187 healthy controls. The validation cohort included 52 patients with preeclampsia and 104 controls. A genome-wide association study was performed to identify putative preeclampsia genes in the discovery cohort, with validation in the validation cohort.
UNASSIGNED: In the discovery cohort, GWAS demonstrated that 19 single-nucleotide polymorphisms (SNPs) were associated with preeclampsia (P < 10-5). The pathway analysis revealed that these 19 SNP representative genes were mainly enriched in the adenylyl cyclase-inhibiting G-protein coupled receptor signaling pathway. After validation in the validation cohort, rs13176432 and rs13210237 remained closely related to preeclampsia (P<0.05). In the combined data set, the frequency of the G allele in rs13176432 was significantly higher in cases with preeclampsia than in controls (P = 5 × 10-6). The frequency of the A allele in rs13210237 was higher in the preeclampsia group (P = 8 × 10-6). The rs13210237 representative genes include HSF2 and GJA1, while the rs13176432 representative gene is TRIM36. There were no differences in genotype distribution between the early-onset and late-onset preeclampsia groups (P > 0.05). Furthermore, rs13210237 and rs13176432 were related to preeclampsia in the adjusted regression model (P < 0.000).
UNASSIGNED: In this study of two independent cohorts, we found that rs13210237 and rs13176432 might be novel preeclampsia-susceptible genetic factors in the Han population in China. However, there was no association between the onset of preeclampsia and these genotypes.
UNASSIGNED: This study aimed to identify common genetic variations associated with preeclampsia in the Chinese Han population through two-stage case‒control studies. The discovery cohort included 92 patients with severe preeclampsia and 187 healthy controls. The validation cohort included 52 patients with preeclampsia and 104 controls. A genome-wide association study was performed to identify putative preeclampsia genes in the discovery cohort, with validation in the validation cohort.
UNASSIGNED: In the discovery cohort, GWAS demonstrated that 19 single-nucleotide polymorphisms (SNPs) were associated with preeclampsia (P < 10-5). The pathway analysis revealed that these 19 SNP representative genes were mainly enriched in the adenylyl cyclase-inhibiting G-protein coupled receptor signaling pathway. After validation in the validation cohort, rs13176432 and rs13210237 remained closely related to preeclampsia (P<0.05). In the combined data set, the frequency of the G allele in rs13176432 was significantly higher in cases with preeclampsia than in controls (P = 5 × 10-6). The frequency of the A allele in rs13210237 was higher in the preeclampsia group (P = 8 × 10-6). The rs13210237 representative genes include HSF2 and GJA1, while the rs13176432 representative gene is TRIM36. There were no differences in genotype distribution between the early-onset and late-onset preeclampsia groups (P > 0.05). Furthermore, rs13210237 and rs13176432 were related to preeclampsia in the adjusted regression model (P < 0.000).
UNASSIGNED: In this study of two independent cohorts, we found that rs13210237 and rs13176432 might be novel preeclampsia-susceptible genetic factors in the Han population in China. However, there was no association between the onset of preeclampsia and these genotypes.
摘要：
■先兆子痫（PE）主要发生在孕妇中，并且是遗传性的。对高加索样品的一些全基因组关联研究(GWAS)已经报道了一些与先兆子痫相关的基因位点。然而,这些研究没有得出一致的结论。以前没有GWAS在中国汉族人群中检查过先兆子痫。
■本研究旨在通过两阶段病例对照研究确定中国汉族人群中与先兆子痫相关的常见遗传变异。发现队列包括92例重度先兆子痫患者和187例健康对照。验证队列包括52例先兆子痫患者和104例对照。进行了全基因组关联研究，以确定发现队列中推定的先兆子痫基因，在验证队列中进行验证。
■在发现队列中，GWAS显示19个单核苷酸多态性（SNP）与先兆子痫有关（P<10-5）。通路分析显示，这19个SNP代表基因主要富集在腺苷酸环化酶抑制G蛋白偶联受体信号通路中。在验证队列中验证后，rs13176432和rs13210237与子痫前期有密切关系(P<0.05)。在组合数据集中，子痫前期患者rs13176432中G等位基因的频率明显高于对照组（P=5×10-6）。子痫前期组rs13210237中A等位基因频率较高(P=8×10-6)。rs13210237的代表性基因包括HSF2和GJA1,而rs13176432的代表性基因是TRIM36。早发型和晚发型子痫前期组基因型分布差异无统计学意义(P>0.05)。此外，校正回归模型中rs13210237和rs13176432与子痫前期相关(P<0.000)。
■在这项两个独立队列的研究中，我们发现rs13210237和rs13176432可能是中国汉族人群易感先兆子痫的新遗传因素。然而,先兆子痫的发病与这些基因型之间没有关联.
■本研究旨在通过两阶段病例对照研究确定中国汉族人群中与先兆子痫相关的常见遗传变异。发现队列包括92例重度先兆子痫患者和187例健康对照。验证队列包括52例先兆子痫患者和104例对照。进行了全基因组关联研究，以确定发现队列中推定的先兆子痫基因，在验证队列中进行验证。
■在发现队列中，GWAS显示19个单核苷酸多态性（SNP）与先兆子痫有关（P<10-5）。通路分析显示，这19个SNP代表基因主要富集在腺苷酸环化酶抑制G蛋白偶联受体信号通路中。在验证队列中验证后，rs13176432和rs13210237与子痫前期有密切关系(P<0.05)。在组合数据集中，子痫前期患者rs13176432中G等位基因的频率明显高于对照组（P=5×10-6）。子痫前期组rs13210237中A等位基因频率较高(P=8×10-6)。rs13210237的代表性基因包括HSF2和GJA1,而rs13176432的代表性基因是TRIM36。早发型和晚发型子痫前期组基因型分布差异无统计学意义(P>0.05)。此外，校正回归模型中rs13210237和rs13176432与子痫前期相关(P<0.000)。
■在这项两个独立队列的研究中，我们发现rs13210237和rs13176432可能是中国汉族人群易感先兆子痫的新遗传因素。然而,先兆子痫的发病与这些基因型之间没有关联.
