Duplication of the SLIT3 locus on 5q35.1 predisposes to major depressive disorder.
Duplication of the SLIT3 locus on 5q35.1 predisposes to major depressive disorder.
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DOI：
10.1371/journal.pone.0015463
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发表时间：
2010-12-01
期刊：
影响因子：
3.7
通讯作者：
Hakonarson H
中科院分区：
文献类型：
--
作者：
Glessner JT;Wang K;Sleiman PM;Zhang H;Kim CE;Flory JH;Bradfield JP;Imielinski M;Frackelton EC;Qiu H;Mentch F;Grant SF;Hakonarson H
重度抑郁症是一种常见的精神和行为障碍。为了发现赋予MDD风险的新变异，我们进行了拷贝数变异（CNV）的全基因组扫描，包括在Perlegen 600K平台上进行基因分型的1，693例MDD病例和4，506例对照。在5q35.1上观察到最显著的位点，包含SLIT 3基因（P = 2×10−3）。 将对照组扩展到Illumina 550 k阵列上的30，000名受试者，我们发现CNV仍然仅限于MDD病例（P = 3.2×10−9）。 在5例不相关的MDD病例中观察到重复，包含646 kb，具有高度相似的断点。SLIT3是基于与Roundabout受体结合的排斥性轴突引导的组成部分。5q35.1的重复是一种高度渗透性变异，占647例携带大CNVs病例子集的0.7%，使用最小10个SNP和100 kb的阈值。本研究利用MDD病例和对照的大型数据集分析具有匹配平台和种族的CNV。SLIT 3重复是一种新的关联，它解释了MDD的一个确定的比例，主要是未知的病因。
Major depressive disorder (MDD) is a common psychiatric and behavioral disorder. To discover novel variants conferring risk to MDD, we conducted a whole-genome scan of copy number variation (CNV), including 1,693 MDD cases and 4,506 controls genotyped on the Perlegen 600K platform. The most significant locus was observed on 5q35.1, harboring the SLIT3 gene (P = 2×10−3). Extending the controls with 30,000 subjects typed on the Illumina 550 k array, we found the CNV to remain exclusive to MDD cases (P = 3.2×10−9). Duplication was observed in 5 unrelated MDD cases encompassing 646 kb with highly similar breakpoints. SLIT3 is integral to repulsive axon guidance based on binding to Roundabout receptors. Duplication of 5q35.1 is a highly penetrant variation accounting for 0.7% of the subset of 647 cases harboring large CNVs, using a threshold of a minimum of 10 SNPs and 100 kb. This study leverages a large dataset of MDD cases and controls for the analysis of CNVs with matched platform and ethnicity. SLIT3 duplication is a novel association which explains a definitive proportion of the largely unknown etiology of MDD.
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影响因子：
20.3
作者：
Zhang, Bing;Dietrich, Ursula M.;Wang, Lianchun
通讯作者：
Wang, Lianchun
影响因子：
14.9
作者：
Diskin SJ;Li M;Hou C;Yang S;Glessner J;Hakonarson H;Bucan M;Maris JM;Wang K
通讯作者：
Wang K
影响因子：
7
作者：
Wang, Kai;Li, Mingyao;Bucan, Maja
通讯作者：
Bucan, Maja
影响因子：
64.8
作者：
Glessner, Joseph T.;Wang, Kai;Cai, Guiqing;Korvatska, Olena;Kim, Cecilia E.;Wood, Shawn;Zhang, Haitao;Estes, Annette;Brune, Camille W.;Bradfield, Jonathan P.;Imielinski, Marcin;Frackelton, Edward C.;Reichert, Jennifer;Crawford, Emily L.;Munson, Jeffrey;Sleiman, Patrick M. A.;Chiavacci, Rosetta;Annaiah, Kiran;Thomas, Kelly;Hou, Cuiping;Glaberson, Wendy;Flory, James;Otieno, Frederick;Garris, Maria;Soorya, Latha;Klei, Lambertus;Piven, Joseph;Meyer, Kacie J.;Anagnostou, Evdokia;Sakurai, Takeshi;Game, Rachel M.;Rudd, Danielle S.;Zurawiecki, Danielle;McDougle, Christopher J.;Davis, Lea K.;Miller, Judith;Posey, David J.;Michaels, Shana;Kolevzon, Alexander;Silverman, Jeremy M.;Bernier, Raphael;Levy, Susan E.;Schultz, Robert T.;Dawson, Geraldine;Owley, Thomas;McMahon, William M.;Wassink, Thomas H.;Sweeney, John A.;Nurnberger, John I., Jr.;Coon, Hilary;Sutcliffe, James S.;Minshew, Nancy J.;Grant, Struan F. A.;Bucan, Maja;Cook, Edwin H., Jr.;Buxbaum, Joseph D.;Devlin, Bernie;Schellenberg, Gerard D.;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
DOI：
10.1083/jcb.200812167
发表时间：
2009-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chan YW;Fava LL;Uldschmid A;Schmitz MH;Gerlich DW;Nigg EA;Santamaria A
通讯作者：
Santamaria A