Integrated genomic analyses in bronchopulmonary dysplasia.
Integrated genomic analyses in bronchopulmonary dysplasia.
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DOI：
10.1016/j.jpeds.2014.09.052
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发表时间：
2015-03
影响因子：
5.1
通讯作者：
Higgins, Rosemary D.
中科院分区：
文献类型：
--
作者：
Ambalavanan, Namasivayam;Cotten, C. Michael;Page, Grier P.;Carlo, Waldemar A.;Murray, Jeffrey C.;Bhattacharya, Soumyaroop;Mariani, Thomas J.;Cuna, Alain C.;Faye-Petersen, Ona M.;Kelly, David;Higgins, Rosemary D.
探讨单核苷酸多态(SNPs)与支气管肺发育不良(BPD)的关系，因为绝经后36周的氧耗量受遗传因素的影响很大。对120万个基因分型的SNPs和另外700万个SNPs进行了全基因组扫描，使用的是极低出生体重婴儿的DNA储存库。对存活者的BPD或死亡、重度BPD或死亡以及重度BPD进行全基因组关联和基因集分析。利用BPD肺组织和小鼠模型中的基因表达来验证特定的靶点。在分析的751名婴儿中，有428名患上BPD或死亡。没有SNPs获得全基因组意义(p<；10−8)，尽管腺苷脱氨酶、CD44和其他基因中的多个SNP略低于p<；10−6。在大约8,000条通路中，75条对bpd/死亡有显著的假发现率，p<；0.001对bpd/死亡有显著意义，95条对重度bpd/死亡有显著意义，90条对存活的严重bpd有显著意义。对于重度BPD/死亡(p=5.68E-08，FDR 0.00019)和存活的重度BPD(p=3.91E-08，FDR 0.00013)，最低FDR219靶点(p=1.41E-08，FDR 9.5E-05)是BPD/死亡和磷酸氧裂解酶(包括腺苷和鸟苷环化酶)活性的靶点。基因表达分析证实BPD患者miR-219和CD44表达显著增加。通路分析证实了已知的肺发育和修复通路(CD44，磷氧裂解酶活性)的参与，并表明新的分子和通路(ADARB2，miR-219的靶标)参与了BPD的遗传易感性。
To identify single nucleotide polymorphisms (SNPs) and pathways associated with bronchopulmonary dysplasia (BPD) because O2 requirement at 36 weeks’ post-menstrual age risk is strongly influenced by heritable factors. A genome-wide scan was conducted on 1.2 million genotyped SNPs, and an additional 7 million imputed SNPs, using a DNA repository of extremely low birth weight infants. Genome-wide association and gene set analysis was performed for BPD or death, severe BPD or death, and severe BPD in survivors. Specific targets were validated using gene expression in BPD lung tissue and in mouse models. Of 751 infants analyzed, 428 developed BPD or died. No SNPs achieved genome-wide significance (p<10−8) although multiple SNPs in adenosine deaminase (ADARB2), CD44, and other genes were just below p<10−6. Of approximately 8000 pathways, 75 were significant at False Discovery Rate (FDR) <0.1 and p<0.001 for BPD/death, 95 for severe BPD/death, and 90 for severe BPD in survivors. The pathway with lowest FDR was miR-219 targets (p=1.41E-08, FDR 9.5E-05) for BPD/death and Phosphorous Oxygen Lyase Activity (includes adenylate and guanylate cyclases) for both severe BPD/death (p=5.68E-08, FDR 0.00019) and severe BPD in survivors (p=3.91E-08, FDR 0.00013). Gene expression analysis confirmed significantly increased miR-219 and CD44 in BPD. Pathway analyses confirmed involvement of known pathways of lung development and repair (CD44, Phosphorus Oxygen Lyase Activity) and indicated novel molecules and pathways (ADARB2, Targets of miR-219) involved in genetic predisposition to BPD.
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影响因子：
5.1
作者：
Carlo, Waldemar A.;McDonald, Scott A.;Tyson, Jon E.;Stoll, Barbara J.;Ehrenkranz, Richard A.;Shankaran, Seetha;Goldberg, Ronald N.;Das, Abhik;Schendel, Diana;Thorsen, Poul;Skogstrand, Kristin;Hougaard, David M.;Oh, William;Laptook, Abbot R.;Duara, Shahnaz;Fanaroff, Avroy A.;Donovan, Edward F.;Korones, Sheldon B.;Stevenson, David K.;Papile, Lu-Ann;Finer, Neil N.;O'Shea, T. Michael;Poindexter, Brenda B.;Wright, Linda L.;Ambalavanan, Namasivayam;Higgins, Rosemary D.
通讯作者：
Higgins, Rosemary D.
影响因子：
4.8
作者：
Recchiuti, Antonio;Krishnamoorthy, Sriram;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
影响因子：
9.8
作者：
Wang, Kai;Li, Mingyao;Bucan, Maja
通讯作者：
Bucan, Maja
影响因子：
3.1
作者：
Chetty, A;Andersson, S;Nielsen, HC
通讯作者：
Nielsen, HC
影响因子：
4.8
作者：
Melcher, T;Maas, S;Seeburg, PH
通讯作者：
Seeburg, PH