Analysis of Intellectual Disability Copy Number Variants for Association With Schizophrenia.
Analysis of Intellectual Disability Copy Number Variants for Association With Schizophrenia.
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DOI：
10.1001/jamapsychiatry.2016.1831
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发表时间：
2016-09-01
期刊：
影响因子：
25.8
通讯作者：
Kirov, George
中科院分区：
文献类型：
--
作者：
Rees, Elliott;Kendall, Kimberley;Pardinas, Antonio F.;Legge, Sophie E.;Pocklington, Andrew;Escott-Price, Valentina;MacCabe, James H.;Collier, David A.;Holmans, Peter;O'Donovan, Michael C.;Owen, Michael J.;Walters, James T. R.;Kirov, George
至少有11种罕见的拷贝数变异（CNVs）已被证明是精神分裂症（SZ）的主要危险因素。这些CNV也增加了其他神经发育障碍的风险，如智力残疾。这是可能的，额外的智力残疾相关的CNV增加SZ的风险，但尚未牵连到SZ，因为以前的研究是不够的。检查是否有其他的CNV涉及智力残疾代表新的SZ风险位点。我们使用单核苷酸多态性（SNP）阵列数据，以评估一组51 CNV涉及智力残疾（不包括已知的SZ位点）在一个大的数据集SZ患者和健康人作为对照组招募在各种设置。我们分析了6934例SZ患者和8751例对照者的新样本，并将这些数据与之前发表的20403例SZ患者和26628例对照者的大型数据集相结合。涉及智力残疾的CNV（不包括已知的SZ CNV）与SZ相关的负担分析。个体智力残疾CNV基因位点与SZ的相关性在20403例（6151 [30.15%]女性）和26628例（14252 [53.52%]女性）对照组中，分析了51例智力残疾CNVs。总的来说，智力残疾的CNVs显著富集于SZ（P = 1.0 × 10−6;比值比[OR]，1.9 [95%CI，1.46-2.49]）。在检测的51个CNV中，19个（37%）在SZ病例中更常见;只有4个（8%）在对照组中更常见（其余28个[55%]位点未观察到）。一个新的位点，16p12.1缺失，经多重检验校正后与SZ显著相关（SZ组发生率为33 [0.16%];对照组发生率为12 [0.05%];校正P = 0.017; OR为3.3; 95%CI为1.61-7.05），2个位点达到标称显著性水平（2q11.2缺失：6 [0.03%] vs 1 [0.004%]; OR，9.3; 95% CI，1.03-447.76;校正P > 0.99; 10q11.21q11.23重复：5 [0.2%] vs 0 [0.03%]; OR，无穷大; 95% CI，1.26-无穷大;校正P = .71）。我们的新数据集还为先前报道的与该疾病相关的11个SZ风险位点和22q11.2重复的保护作用提供了独立的支持。大部分与智力残疾有关的CNV位点是SZ的危险因素，但现有的样本量排除了对其他个体位点的统计学确认。
At least 11 rare copy number variants (CNVs) have been shown to be major risk factors for schizophrenia (SZ). These CNVs also increase the risk for other neurodevelopmental disorders, such as intellectual disability. It is possible that additional intellectual disability–associated CNVs increase the risk for SZ but have not yet been implicated in SZ because of previous studies being underpowered. To examine whether additional CNVs implicated in intellectual disability represent novel SZ risk loci. We used single-nucleotide polymorphism (SNP) array data to evaluate a set of 51 CNVs implicated in intellectual disability (excluding the known SZ loci) in a large data set of patients with SZ and healthy persons serving as controls recruited in a variety of settings. We analyzed a new sample of 6934 individuals with SZ and 8751 controls and combined those data with previously published large data sets for a total of 20 403 cases of SZ and 26 628 controls. Burden analysis of CNVs implicated in intellectual disability (excluding known SZ CNVs) for association with SZ. Association of individual intellectual disability CNV loci with SZ. Of data on the 20 403 cases (6151 [30.15%] female) and 26 628 controls (14 252 [53.52%] female), 51 intellectual disability CNVs were analyzed. Collectively, intellectual disability CNVs were significantly enriched for SZ (P = 1.0 × 10−6; odds ratio [OR], 1.9 [95% CI, 1.46-2.49]). Of the 51 CNVs tested, 19 (37%) were more common in SZ cases; only 4 (8%) were more common in controls (no observations were made for the remaining 28 [55%] loci). One novel locus, deletion at 16p12.1, was significantly associated with SZ after correction for multiple testing (rate in SZ, 33 [0.16%]; rate in controls, 12 [0.05%]; corrected P = .017; OR, 3.3; 95% CI, 1.61-7.05), and 2 loci reached nominal levels of significance (deletions at 2q11.2: 6 [0.03%] vs 1 [0.004%]; OR, 9.3; 95% CI, 1.03-447.76; corrected P > .99; and duplications at 10q11.21q11.23: 5 [0.2%] vs 0 [0.03%]; OR, infinity; 95% CI, 1.26-infinity; corrected P = .71). Our new data set also provided independent support for the 11 SZ risk loci previously reported to be associated with the disorder and for the protective effect of 22q11.2 duplication. A large proportion of CNV loci implicated in intellectual disability are risk factors for SZ, but the available sample size precludes statistical confirmation for additional individual loci.
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DOI：
10.1192/bjp.bp.113.131052
发表时间：
2014-02
期刊：
The British journal of psychiatry : the journal of mental science
影响因子：
--
作者：
Rees E;Walters JT;Georgieva L;Isles AR;Chambert KD;Richards AL;Mahoney-Davies G;Legge SE;Moran JL;McCarroll SA;O'Donovan MC;Owen MJ;Kirov G
通讯作者：
Kirov G
影响因子：
4.6
作者：
Han J;Walters JT;Kirov G;Pocklington A;Escott-Price V;Owen MJ;Holmans P;O'Donovan MC;Rees E
通讯作者：
Rees E
影响因子：
64.8
作者：
Stone, Jennifer L.;O'Donovan, Michael C.;Gurling, Hugh;Kirov, George K.;Blackwood, Douglas H. R.;Corvin, Aiden;Craddock, Nick J.;Gill, Michael;Hultman, Christina M.;Lichtenstein, Paul;McQuillin, Andrew;Pato, Carlos N.;Ruderfer, Douglas M.;Owen, Michael J.;St Clair, David;Sullivan, Patrick F.;Sklar, Pamela;Purcell, Shaun M.;Scolnick, E. M.;Holmans, P. A.;Georgieva, L.;Nikolov, I.;Norton, N.;Williams, H.;Williams, N. M.;Toncheva, D.;Milanova, V.;Thelander, E. F.;Morris, D. W.;O'Dushlaine, C. T.;Kenny, E.;Waddington, J. L.;Choudhury, K.;Datta, S.;Pimm, J.;Thirumalai, S.;Puri, V.;Krasucki, R.;Lawrence, J.;Quested, D.;Bass, N.;Curtis, D.;Crombie, C.;Fraser, G.;Kwan, S. L.;Muir, W. J.;McGhee, K. A.;Pickard, B.;Malloy, P.;Maclean, A. W.;Van Beck, M.;Visscher, P. M.;Macgregor, S.;Pato, M. T.;Medeiros, H.;Middleton, F.;Carvalho, C.;Morley, C.;Fanous, A.;Conti, D.;Knowles, J. A.;Ferreira, C. P.;Azevedo, M. H.;McCarroll, S. A.;Gates, C.;Daly, M. J.;Sklar, P.
通讯作者：
Sklar, P.
影响因子：
64.8
作者：
Ripke, Stephan;Neale, Benjamin M.;Corvin, Aiden;Walters, James T. R.;Farh, Kai-How;Holmans, Peter A.;Lee, Phil;Bulik-Sullivan, Brendan;Collier, David A.;Huang, Hailiang;Pers, Tune H.;Agartz, Ingrid;Agerbo, Esben;Albus, Margot;Alexander, Madeline;Amin, Farooq;Bacanu, Silviu A.;Begemann, Martin;Belliveau, Richard A., Jr.;Bene, Judit;Bergen, Sarah E.;Bevilacqua, Elizabeth;Bigdeli, Tim B.;Black, Donald W.;Bruggeman, Richard;Buccola, Nancy G.;Buckner, Randy L.;Byerley, William;Cahn, Wiepke;Cai, Guiqing;Campion, Dominique;Cantor, Rita M.;Carr, Vaughan J.;Carrera, Noa;Catts, Stanley V.;Chambert, Kimberly D.;Chan, Raymond C. K.;Chen, Ronald Y. L.;Chen, Eric Y. H.;Cheng, Wei;Cheung, Eric F. C.;Chong, Siow Ann;Cloninger, C. Robert;Cohen, David;Cohen, Nadine;Cormican, Paul;Craddock, Nick;Crowley, James J.;Curtis, David;Davidson, Michael;Davis, Kenneth L.;Degenhardt, Franziska;Del Favero, Jurgen;Demontis, Ditte;Dikeos, Dimitris;Dinan, Timothy;Djurovic, Srdjan;Donohoe, Gary;Drapeau, Elodie;Duan, Jubao;Dudbridge, Frank;Durmishi, Naser;Eichhammer, Peter;Eriksson, Johan;Escott-Price, Valentina;Essioux, Laurent;Fanous, Ayman H.;Farrell, Martilias S.;Frank, Josef;Franke, Lude;Freedman, Robert;Freimer, Nelson B.;Friedl, Marion;Friedman, Joseph I.;Fromer, Menachem;Genovese, Giulio;Georgieva, Lyudmila;Giegling, Ina;Giusti-Rodriguez, Paola;Godard, Stephanie;Goldstein, Jacqueline I.;Golimbet, Vera;Gopal, Srihari;Gratten, Jacob;de Haan, Lieuwe;Hammer, Christian;Hamshere, Marian L.;Hansen, Mark;Hansen, Thomas;Haroutunian, Vahram;Hartmann, Annette M.;Henskens, Frans A.;Herms, Stefan;Hirschhorn, Joel N.;Hoffmann, Per;Hofman, Andrea;Hollegaard, Mads V.;Hougaard, David M.;Ikeda, Masashi;Joa, Inge;Julia, Antonio;Kahn, Rene S.;Kalaydjieva, Luba;Karachanak-Yankova, Sena;Karjalainen, Juha;Kavanagh, David;Keller, Matthew C.;Kennedy, James L.;Khrunin, Andrey;Kim, Yunjung;Klovins, Janis;Knowles, James A.;Konte, Bettina;Kucinskas, Vaidutis;Kucinskiene, Zita Ausrele;Kuzelova-Ptackova, Hana;Kahler, Anna K.;Laurent, Claudine;Keong, Jimmy Lee Chee;Lee, S. Hong;Legge, Sophie E.;Lerer, Bernard;Li, Miaoxin;Li, Tao;Liang, Kung-Yee;Lieberman, Jeffrey;Limborska, Svetlana;Loughland, Carmel M.;Lubinski, Jan;Lonnqvist, Jouko;Macek, Milan, Jr.;Magnusson, Patrik K. E.;Maher, Brion S.;Maier, Wolfgang;Mallet, Jacques;Marsal, Sara;Mattheisen, Manuel;Mattingsdal, Morten;McCarley, Robert W.;McDonald, Colm;McIntosh, Andrew M.;Meier, Sandra;Meijer, Carin J.;Melegh, Bela;Melle, Ingrid;Mesholam-Gately, Raquelle I.;Metspalu, Andres;Michie, Patricia T.;Milani, Lili;Milanova, Vihra;Mokrab, Younes;Morris, Derek W.;Mors, Ole;Murphy, Kieran C.;Murray, Robin M.;Myin-Germeys, Inez;Mueller-Myhsok, Bertram;Nelis, Mari;Nenadic, Igor;Nertney, Deborah A.;Nestadt, Gerald;Nicodemus, Kristin K.;Nikitina-Zake, Liene;Nisenbaum, Laura;Nordin, Annelie;O'Callaghan, Eadbhard;O'Dushlaine, Colm;O'Neill, F. Anthony;Oh, Sang-Yun;Olincy, Ann;Olsen, Line;Van Os, Jim;Pantelis, Christos;Papadimitriou, George N.;Papiol, Sergi;Parkhomenko, Elena;Pato, Michele T.;Paunio, Tiina;Pejovic-Milovancevic, Milica;Perkins, Diana O.;Pietilainen, Olli;Pimm, Jonathan;Pocklington, Andrew J.;Powell, John;Price, Alkes;Pulver, Ann E.;Purcell, Shaun M.;Quested, Digby;Rasmussen, Henrik B.;Reichenberg, Abraham;Reimers, Mark A.;Richards, Alexander L.;Roffman, Joshua L.;Roussos, Panos;Ruderfer, Douglas M.;Salomaa, Veikko;Sanders, Alan R.;Schall, Ulrich;Schubert, Christian R.;Schulze, Thomas G.;Schwab, Sibylle G.;Scolnick, Edward M.;Scott, Rodney J.;Seidman, Larry J.;Shi, Jianxin;Sigurdsson, Engilbert;Silagadze, Teimuraz;Silverman, Jeremy M.;Sim, Kang;Slominsky, Petr;Smoller, Jordan W.;So, Hon-Cheong;Spencer, Chris C. A.;Stahl, Eli A.;Stefansson, Hreinn;Steinberg, Stacy;Stogmann, Elisabeth;Straub, Richard E.;Strengman, Eric;Strohmaier, Jana;Stroup, T. Scott;Subramaniam, Mythily;Suvisaari, Jaana;Svrakic, Dragan M.;Szatkiewicz, Jin P.;Soderman, Erik;Thirumalai, Srinivas;Toncheva, Draga;Tosato, Sarah;Veijola, Juha;Waddington, John;Walsh, Dermot;Wang, Dai;Wang, Qiang;Webb, Bradley T.;Weiser, Mark;Wildenauer, Dieter B.;Williams, Nigel M.;Williams, Stephanie;Witt, Stephanie H.;Wolen, Aaron R.;Wong, Emily H. M.;Wormley, Brandon K.;Xi, Hualin Simon;Zai, Clement C.;Zheng, Xuebin;Zimprich, Fritz;Wray, Naomi R.;Stefansson, Kari;Visscher, Peter M.;Adolfsson, Rolf;Andreassen, Ole A.;Blackwood, Douglas H. R.;Bramon, Elvira;Buxbaum, Joseph D.;Borglum, Anders D.;Cichon, Sven;Darvasi, Ariel;Domenici, Enrico;Ehrenreich, Hannelore;Esko, Tonu;Gejman, Pablo V.;Gill, Michael;Gurling, Hugh;Hultman, Christina M.;Iwata, Nakao;Jablensky, Assen V.;Jonsson, Erik G.;Kendler, Kenneth S.;Kirov, George;Knight, Jo;Lencz, Todd;Levinson, Douglas F.;Li, Qingqin S.;Liu, Jianjun;Malhotra, Anil K.;McCarroll, Steven A.;McQuillin, Andrew;Moran, Jennifer L.;Mortensen, Preben B.;Mowry, Bryan J.;Noethen, Markus M.;Ophoff, Roel A.;Owen, Michael J.;Palotie, Aarno;Pato, Carlos N.;Petryshen, Tracey L.;Posthuma, Danielle;Rietschel, Marcella;Riley, Brien P.;Rujescu, Dan;Sham, Pak C.;Sklar, Pamela;St Clair, David;Weinberger, Daniel R.;Wendland, Jens R.;Werge, Thomas;Daly, Mark J.;Sullivan, Patrick F.;O'Donovan, Michael C.
通讯作者：
O'Donovan, Michael C.
影响因子：
10.6
作者：
Kirov, George;Rees, Elliott;Walters, James T. R.;Escott-Price, Valentina;Georgieva, Lyudmila;Richards, Alexander L.;Chambert, Kimberly D.;Davies, Gerwyn;Legge, Sophie E.;Moran, Jennifer L.;McCarroll, Steven A.;O'Donovan, Michael C.;Owen, Michael J.
通讯作者：
Owen, Michael J.