Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.
Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.
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DOI：
10.1016/j.jaac.2014.04.022
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发表时间：
2014-08
影响因子：
13.3
通讯作者：
Scharf, Jeremiah M.
中科院分区：
文献类型：
--
作者：
McGrath, Lauren M.;Yu, Dongmei;Marshall, Christian;Davis, Lea K.;Thiruvahindrapuram, Bhooma;Li, Bingbin;Cappi, Carolina;Gerber, Gloria;Wolf, Aaron;Schroeder, Frederick A.;Osiecki, Lisa;O'Dushlaine, Colm;Kirby, Andrew;Illmann, Cornelia;Haddad, Stephen;Gallagher, Patience;Fagerness, Jesen A.;Barr, Cathy L.;Bellodi, Laura;Benarroch, Fortu;Bienvenu, O. Joseph;Black, Donald W.;Bloch, Michael H.;Bruun, Ruth D.;Budman, Cathy L.;Camarena, Beatriz;Cath, Danielle C.;Cavallini, Maria C.;Chouinard, Sylvain;Coric, Vladimir;Cullen, Bernadette;Delorme, Richard;Denys, Damiaan;Derks, Eske M.;Dion, Yves;Rosario, Maria C.;Eapen, Valsama;Evans, Patrick;Falkai, Peter;Fernandez, Thomas V.;Garrido, Helena;Geller, Daniel;Grabe, Hans J.;Grados, Marco A.;Greenberg, Benjamin D.;Gross-Tsur, Varda;Gruenblatt, Edna;Heiman, Gary A.;Hemmings, Sian M. J.;Herrera, Luis D.;Hounie, Ana G.;Jankovic, Joseph;Kennedy, James L.;King, Robert A.;Kurlan, Roger;Lanzagorta, Nuria;Leboyer, Marion;Leckman, James F.;Lennertz, Leonhard;Lochner, Christine;Lowe, Thomas L.;Lyon, Gholson J.;Macciardi, Fabio;Maier, Wolfgang;McCracken, James T.;McMahon, William;Murphy, Dennis L.;Naarden, Allan L.;Neale, Benjamin M.;Nurmi, Erika;Pakstis, Andrew J.;Pato, Michele T.;Pato, Carlos N.;Piacentini, John;Pittenger, Christopher;Pollak, Yehuda;Reus, Victor I.;Richter, Margaret A.;Riddle, Mark;Robertson, Mary M.;Rosenberg, David;Rouleau, Guy A.;Ruhrmann, Stephan;Sampaio, Aline S.;Samuels, Jack;Sandor, Paul;Sheppard, Brooke;Singer, Harvey S.;Smit, Jan H.;Stein, Dan J.;Tischrield, Jay A.;Vallada, Homero;Veenstra-VanderWeele, Jeremy;Walitza, Susanne;Wang, Ying;Wendfand, Jens R.;Shugart, Yin Yao;Miguel, Euripedes C.;Nicolini, Humberto;Oostra, Ben A.;Moessner, Rainald;Wagner, Michael;Ruiz-Linares, Andres;Heutink, Peter;Nestadt, Gerald;Freimer, Nelson;Petryshen, Tracey;Posthuma, Danielle;Jenike, Michael A.;Cox, Nancy J.;Hanna, Gregory L.;Brentani, Helena;Scherer, Stephen W.;Arnold, Paul D.;Stewart, S. Evelyn;Mathews, Carol A.;Knowles, James A.;Cook, Edwin H.;Pauls, David L.;Wang, Kai;Scharf, Jeremiah M.
强迫症(OCD)和抽动秽语综合征(TS)是遗传性神经发育障碍，具有部分相同的遗传病因。这项研究是第一次对强迫症大(>；500kb)、罕见(<；1%)拷贝数变异(CNV)进行全基因组研究，也是迄今为止在TS中进行的最大的全基因组CNV分析。初步分析采用交叉无序设计，对2,699名患者(1,613名强迫症患者，1,086名TS患者)和1,789名对照组进行了研究。父母数据有助于对348个强迫症三人组进行从头分析。虽然在交叉疾病分析或二次疾病特异性分析中没有检测到全球CNV负担，但以前与其他神经发育障碍相关的大量缺失的负担增加了3.3倍(p=0.09)。这些神经发育缺失中有一半位于16p13.11(5个患者缺失：0个对照缺失，在当前研究中p=0.08，与已发表的对照相比p=0.025)。新发现3个16p13.11缺失，进一步支持了该区域的病因学意义。强迫症的总发病率为1.4%，介于对照组(0.7%)和自闭症或精神分裂症(2-4%)公布的发病率之间。几条趋同的证据表明，16p13.11基因缺失与强迫症有关，而在TS中起作用的证据较弱。TS和强迫症患者总体神经发育CNV负荷增加的趋势表明，以前与其他神经发育障碍相关的缺失也可能与这些表型有关。
Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable, neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. The primary analyses utilized a cross-disorder design for 2,699 patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p=.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 patient deletions: 0 control deletions, p=0.08 in current study, p=0.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support to the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in autism or schizophrenia (2–4%). Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.
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影响因子：
46.9
作者：
通讯作者：
--
影响因子：
16.2
作者：
Malhotra D;McCarthy S;Michaelson JJ;Vacic V;Burdick KE;Yoon S;Cichon S;Corvin A;Gary S;Gershon ES;Gill M;Karayiorgou M;Kelsoe JR;Krastoshevsky O;Krause V;Leibenluft E;Levy DL;Makarov V;Bhandari A;Malhotra AK;McMahon FJ;Nöthen MM;Potash JB;Rietschel M;Schulze TG;Sebat J
通讯作者：
Sebat J
影响因子：
64.8
作者：
Cook, Edwin H., Jr.;Scherer, Stephen W.
通讯作者：
Scherer, Stephen W.
影响因子：
9.8
作者：
Miller, David T.;Adam, Margaret P.;Ledbetter, David H.
通讯作者：
Ledbetter, David H.
DOI：
10.1016/j.jaac.2011.11.004
发表时间：
2012-02
影响因子：
13.3
作者：
Scharf JM;Miller LL;Mathews CA;Ben-Shlomo Y
通讯作者：
Ben-Shlomo Y