Genetic variations and risk of placental abruption: A genome-wide association study and meta-analysis of genome-wide association studies.
Genetic variations and risk of placental abruption: A genome-wide association study and meta-analysis of genome-wide association studies.
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遗传变异和胎盘破裂的风险：全基因组关联研究和全基因组关联研究的荟萃分析。
DOI：
10.1016/j.placenta.2018.04.008
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发表时间：
2018-06
期刊：
影响因子：
3.8
通讯作者：
Williams MA
中科院分区：
文献类型：
--
作者：
Workalemahu T;Enquobahrie DA;Gelaye B;Sanchez SE;Garcia PJ;Tekola-Ayele F;Hajat A;Thornton TA;Ananth CV;Williams MA
越来越多的流行病学证据表明胎盘早剥（PA）具有很强的遗传易感性。然而，与PA相关的基因表征仍然不完整。我们进行了PA的全基因组关联研究（GWAS）和GWAS的荟萃分析。胎盘早剥遗传流行病学（PAGE）研究是在秘鲁利马进行的一项基于人群的PA病例对照研究，参与者使用Illumina HumanCore-24 BeadChip平台进行基因分型。利用1000个基因组参考面板进行基因型估算，并对通过质量控制的490万个snp进行分析。我们对PAGE参与者（507例PA病例和1090例对照）进行了GWAS，并对2512名参与者（959例PA病例和1553例对照）进行了GWAS荟萃分析，其中包括PAGE和先前报道的秘鲁胎盘早剥流行病学（PAPE）研究。我们拟合了人口分层调整后的逻辑回归模型和使用反方差加权的固定效应荟萃分析。与PA相关（p值< 5e-5）的独立位点包括ABCC8中的rs4148646和rs2074311， ZNF28中的rs7249210、rs7250184、rs7249100和rs10401828， CTNND2中的rs11133659， PAGE GWAS中KCNJ11附近的rs2074314和rs35271178。同样，GWAS meta分析中与PA相关的独立基因座包括IRX1附近的rs76258369， ADAM12中的rs7094759和rs12264492。这些基因的功能分析显示滋养细胞样细胞相互作用，以及参与内分泌系统疾病、心血管疾病和细胞功能的网络。我们确定了几个可能在PA风险中起作用的遗传位点和相关功能。了解PA病理生理机制的遗传因素可能有助于预防和早期诊断。
Accumulating epidemiological evidence points to strong genetic susceptibility to placental abruption (PA). However, characterization of genes associated with PA remains incomplete. We conducted a genome-wide association study (GWAS) of PA and a meta-analysis of GWAS. Participants of the Placental Abruption Genetic Epidemiology (PAGE) study, a population based case-control study of PA conducted in Lima, Peru, were genotyped using the Illumina HumanCore-24 BeadChip platform. Genotypes were imputed using the 1000 genomes reference panel, and >4.9 million SNPs that passed quality control were analyzed. We performed a GWAS in PAGE participants (507 PA cases and 1,090 controls) and a GWAS meta-analysis in 2,512 participants (959 PA cases and 1,553 controls) that included PAGE and the previously reported Peruvian Abruptio Placentae Epidemiology (PAPE) study. We fitted population stratification-adjusted logistic regression models and fixed-effects meta-analyses using inverse-variance weighting. Independent loci (linkage-disequilibrium<0.80) suggestively associated with PA (P-value< 5e-5) included rs4148646 and rs2074311 in ABCC8, rs7249210, rs7250184, rs7249100 and rs10401828 in ZNF28, rs11133659 in CTNND2, and rs2074314 and rs35271178 near KCNJ11 in the PAGE GWAS. Similarly, independent loci suggestively associated with PA in the GWAS meta-analysis included rs76258369 near IRX1, and rs7094759 and rs12264492 in ADAM12. Functional analyses of these genes showed trophoblast-like cell interaction, as well as networks involved in endocrine system disorders, cardiovascular diseases, and cellular function. We identified several genetic loci and related functions that may play a role in PA risk. Understanding genetic factors underlying pathophysiological mechanisms of PA may facilitate prevention and early diagnostic efforts.
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影响因子：
4.3
作者：
Haghvirdizadeh P;Mohamed Z;Abdullah NA;Haghvirdizadeh P;Haerian MS;Haerian BS
通讯作者：
Haerian BS
影响因子：
14.9
作者：
Cariaso M;Lennon G
通讯作者：
Lennon G
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
DOI：
10.1016/s0002-9378(97)70205-9
发表时间：
1997-08-01
影响因子：
9.8
作者：
DizonTomson, DS;Meline, L;Ward, K
通讯作者：
Ward, K
DOI：
10.1111/j.1471-0528.1992.tb13848.x
发表时间：
1992-08-01
期刊：
BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY
影响因子：
--
作者：
DOMMISSE, J;TILTMAN, AJ
通讯作者：
TILTMAN, AJ