Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia.
Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia.
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DOI：
10.1038/mp.2011.117
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发表时间：
2012-10
影响因子：
11
通讯作者：
Posthuma, D.
中科院分区：
文献类型：
--
作者：
Lips, E. S.;Cornelisse, L. N.;Toonen, R. F.;Min, J. L.;Hultman, C. M.;Holmans, P. A.;O'Donovan, M. C.;Purcell, S. M.;Smit, A. B.;Verhage, M.;Sullivan, P. F.;Visscher, P. M.;Posthuma, D.
精神分裂症是一种高度遗传性疾病，具有多基因遗传模式，人群患病率约为1%。先前的研究表明，精神分裂症中存在突触功能障碍。我们使用功能基因组分析，测试了4673例和4965例健康对照者中专家整理的突触基因群中遗传变异与精神分裂症的累积关联。识别具有相似细胞功能的基因群，而不是孤立的基因，可能对寻找其他药物靶点具有临床意义。我们发现，一组1026个突触基因与精神分裂症的风险显著相关（P=7.6 × 10−11），并且比随机抽取的100个匹配的遗传变异对照组的相关性更强（P<0.01）。随后对突触亚群的分析表明，最强的关联信号来自三个突触基因群：细胞内信号转导（P=2.0 × 10−4）、兴奋性（P=9.0 × 10−4）和细胞粘附和跨突触信号（P=2.4 × 10−3）。这些结果与突触功能障碍在精神分裂症中的作用一致，并暗示突触细胞内信号转导、突触兴奋性和细胞粘附以及跨突触信号传导的受损在精神分裂症的病理中起作用。
Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of ∼1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association of genetic variants in expert-curated synaptic gene groups with schizophrenia in 4673 cases and 4965 healthy controls, using functional gene group analysis. Identifying groups of genes with similar cellular function rather than genes in isolation may have clinical implications for finding additional drug targets. We found that a group of 1026 synaptic genes was significantly associated with the risk of schizophrenia (P=7.6 × 10−11) and more strongly associated than 100 randomly drawn, matched control groups of genetic variants (P<0.01). Subsequent analysis of synaptic subgroups suggested that the strongest association signals are derived from three synaptic gene groups: intracellular signal transduction (P=2.0 × 10−4), excitability (P=9.0 × 10−4) and cell adhesion and trans-synaptic signaling (P=2.4 × 10−3). These results are consistent with a role of synaptic dysfunction in schizophrenia and imply that impaired intracellular signal transduction in synapses, synaptic excitability and cell adhesion and trans-synaptic signaling play a role in the pathology of schizophrenia.
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影响因子：
64.8
作者：
Stefansson, Hreinn;Ophoff, Roel A.;Steinberg, Stacy;Andreassen, Ole A.;Cichon, Sven;Rujescu, Dan;Werge, Thomas;Pietilainen, Olli P. H.;Mors, Ole;Mortensen, Preben B.;Sigurdsson, Engilbert;Gustafsson, Omar;Nyegaard, Mette;Tuulio-Henriksson, Annamari;Ingason, Andres;Hansen, Thomas;Suvisaari, Jaana;Lonnqvist, Jouko;Paunio, Tiina;Borglum, Anders D.;Hartmann, Annette;Fink-Jensen, Anders;Nordentoft, Merete;Hougaard, David;Norgaard-Pedersen, Bent;Bottcher, Yvonne;Olesen, Jes;Breuer, Rene;Moeller, Hans-Jurgen;Giegling, Ina;Rasmussen, Henrik B.;Timm, Sally;Mattheisen, Manuel;Bitter, Istvan;Rethelyi, Janos M.;Magnusdottir, Brynja B.;Sigmundsson, Thordur;Olason, Pall;Mason, Gisli;Gulcher, Jeffrey R.;Haraldsson, Magnus;Fossdal, Ragnheidur;Thorgeirsson, Thorgeir E.;Thorsteinsdottir, Unnur;Ruggeri, Mirella;Tosato, Sarah;Franke, Barbara;Strengman, Eric;Kiemeney, Lambertus A.;Melle, Ingrid;Djurovic, Srdjan;Abramova, Lilia;Kaleda, Vasily;Sanjuan, Julio;de Frutos, Rosa;Bramon, Elvira;Vassos, Evangelos;Fraser, Gillian;Ettinger, Ulrich;Picchioni, Marco;Walker, Nicholas;Toulopoulou, Timi;Need, Anna C.;Ge, Dongliang;Yoon, Joeng Lim;Shianna, Kevin V.;Freimer, Nelson B.;Cantor, Rita M.;Murray, Robin;Kong, Augustine;Golimbet, Vera;Carracedo, Angel;Arango, Celso;Costas, Javier;Joensson, Erik G.;Terenius, Lars;Agartz, Ingrid;Petursson, Hannes;Nothen, Markus M.;Rietschel, Marcella;Matthews, Paul M.;Muglia, Pierandrea;Peltonen, Leena;St Clair, David;Goldstein, David B.;Stefansson, Kari;Collier, David A.
通讯作者：
Collier, David A.
影响因子：
--
作者：
Sullivan, PF;Kendler, KS;Neale, MC
通讯作者：
Neale, MC
影响因子：
11
作者：
Mowry, BJ;Holmans, PA;Levinson, DF
通讯作者：
Levinson, DF
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick
DOI：
10.1073/pnas.0903103106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Hindorff, Lucia A.;Sethupathy, Praveen;Manolio, Teri A.
通讯作者：
Manolio, Teri A.