Large recurrent microdeletions associated with schizophrenia.
Large recurrent microdeletions associated with schizophrenia.
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与精神分裂症相关的大的复发性微缺失
DOI：
10.1038/nature07229
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发表时间：
2008-09-11
期刊：
影响因子：
64.8
通讯作者：
Stefansson, Kari
中科院分区：
文献类型：
--
作者：
Stefansson, Hreinn;Rujescu, Dan;Cichon, Sven;Pietilainen, Olli P. H.;Ingason, Andres;Steinberg, Stacy;Fossdal, Ragnheidur;Sigurdsson, Engilbert;Sigmundsson, Thordur;Buizer-Voskamp, Jacobine E.;Hansen, Thomas;Jakobsen, Klaus D.;Muglia, Pierandrea;Francks, Clyde;Matthews, Paul M.;Gylfason, Arnaldur;Halldorsson, Bjarni V.;Gudbjartsson, Daniel;Thorgeirsson, Thorgeir E.;Sigurdsson, Asgeir;Jonasdottir, Adalbjorg;Jonasdottir, Aslaug;Bjornsson, Asgeir;Mattiasdottir, Sigurborg;Blondal, Thorarinn;Haraldsson, Magnus;Magnusdottir, Brynja B.;Giegling, Ina;Moeller, Hans-Juergen;Hartmann, Annette;Shianna, Kevin V.;Ge, Dongliang;Need, Anna C.;Crombie, Caroline;Fraser, Gillian;Walker, Nicholas;Lonnqvist, Jouko;Suvisaari, Jaana;Tuulio-Henriksson, Annamarie;Paunio, Tiina;Toulopoulou, Timi;Bramon, Elvira;Di Forti, Marta;Murray, Robin;Ruggeri, Mirella;Vassos, Evangelos;Tosato, Sarah;Walshe, Muriel;Li, Tao;Vasilescu, Catalina;Muehleisen, Thomas W.;Wang, August G.;Ullum, Henrik;Djurovic, Srdjan;Melle, Ingrid;Olesen, Jes;Kiemeney, Lambertus A.;Franke, Barbara;Sabatti, Chiara;Freimer, Nelson B.;Gulcher, Jeffrey R.;Thorsteinsdottir, Unnur;Kong, Augustine;Andreassen, Ole A.;Ophoff, Roel A.;Georgi, Alexander;Rietschel, Marcella;Werge, Thomas;Petursson, Hannes;Goldstein, David B.;Noethen, Markus M.;Peltonen, Leena;Collier, David A.;St Clair, David;Stefansson, Kari
与严重精神障碍相关的生育力下降，对风险等位基因施加了负选择压力，这可能部分解释了为什么没有发现常见的变异，这些变异会导致自闭症，精神分裂症和精神发育迟滞等疾病的风险。因此，罕见变异可能比以前假设的占整体遗传风险的更大比例。与罕见的单核苷酸突变相反，罕见的拷贝数变异（CNVs）可以使用全基因组单核苷酸多态性阵列检测。这导致了与精神发育迟滞和自闭症相关的CNV的鉴定。在全基因组搜索与精神分裂症相关的CNVs中，我们使用基于人群的样本，通过分析父母向后代的9，878次传播来识别新的CNVs。在1，433名精神分裂症患者和33，250名对照者的样本中，对鉴定出的66个de novoCNVs进行了相关性测试。在第一个样本（I期）中显示与精神分裂症名义相关的1q21.1、15q11.2和15q13.3处的三个缺失在第二个样本（3,285例病例和7,951例对照）中进行了随访（II期）。在合并样本中，所有三种缺失均与精神分裂症和相关精神病显著相关。识别这些罕见的、反复出现的风险变异，这些变异在多个创始人中独立发生，并受到负选择的影响，这本身就很重要。CNV分析也可能为鉴定精神分裂症相关基因和途径中额外的和更普遍的风险变异指明了方向。
Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation,and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identifyde novoCNVs by analysing 9,878 transmissions from parents to offspring. The 66de novoCNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.
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染色体微阵列分析的临床实施：2513例产后病例的摘要。
影响因子：
3.7
作者：
Lu, Xinyan;Shaw, Chad A.;Patel, Ankita;Li, Jiangzhen;Cooper, M. Lance;Wells, William R.;Sullivan, Cathy M.;Sahoo, Trilochan;Yatsenko, Svetlana A.;Bacino, Carlos A.;Stankiewicz, Pawel;Ou, Zhishu;Chinault, A. Craig;Beaudet, Arthur L.;Lupski, James R.;Cheung, Sau W.;Ward, Patricia A.
通讯作者：
Ward, Patricia A.
影响因子：
158.5
作者：
Weiss, Lauren A.;Shen, Yiping;Daly, Mark J.
通讯作者：
Daly, Mark J.
影响因子：
9.8
作者：
Gurling, HMD;Kalsi, G;Curtis, D
通讯作者：
Curtis, D
DOI：
10.1097/01.dbp.0000267563.18952.c9
发表时间：
2007-04-01
影响因子：
2.4
作者：
Nowicki, Stephen T.;Tassone, Flora;Hagerman, Randi J.
通讯作者：
Hagerman, Randi J.
影响因子：
2
作者：
Erdogan, Fikret;Ullmann, Reinhard;Tzschach, Andreas
通讯作者：
Tzschach, Andreas