Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects.
Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects.
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DOI：
10.1038/ng.3725
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发表时间：
2017-01
期刊：
影响因子：
30.8
通讯作者：
CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium
中科院分区：
文献类型：
--
作者：
Marshall CR;Howrigan DP;Merico D;Thiruvahindrapuram B;Wu W;Greer DS;Antaki D;Shetty A;Holmans PA;Pinto D;Gujral M;Brandler WM;Malhotra D;Wang Z;Fajarado KVF;Maile MS;Ripke S;Agartz I;Albus M;Alexander M;Amin F;Atkins J;Bacanu SA;Belliveau RA Jr;Bergen SE;Bertalan M;Bevilacqua E;Bigdeli TB;Black DW;Bruggeman R;Buccola NG;Buckner RL;Bulik-Sullivan B;Byerley W;Cahn W;Cai G;Cairns MJ;Campion D;Cantor RM;Carr VJ;Carrera N;Catts SV;Chambert KD;Cheng W;Cloninger CR;Cohen D;Cormican P;Craddock N;Crespo-Facorro B;Crowley JJ;Curtis D;Davidson M;Davis KL;Degenhardt F;Del Favero J;DeLisi LE;Dikeos D;Dinan T;Djurovic S;Donohoe G;Drapeau E;Duan J;Dudbridge F;Eichhammer P;Eriksson J;Escott-Price V;Essioux L;Fanous AH;Farh KH;Farrell MS;Frank J;Franke L;Freedman R;Freimer NB;Friedman JI;Forstner AJ;Fromer M;Genovese G;Georgieva L;Gershon ES;Giegling I;Giusti-Rodríguez P;Godard S;Goldstein JI;Gratten J;de Haan L;Hamshere ML;Hansen M;Hansen T;Haroutunian V;Hartmann AM;Henskens FA;Herms S;Hirschhorn JN;Hoffmann P;Hofman A;Huang H;Ikeda M;Joa I;Kähler AK;Kahn RS;Kalaydjieva L;Karjalainen J;Kavanagh D;Keller MC;Kelly BJ;Kennedy JL;Kim Y;Knowles JA;Konte B;Laurent C;Lee P;Lee SH;Legge SE;Lerer B;Levy DL;Liang KY;Lieberman J;Lönnqvist J;Loughland CM;Magnusson PKE;Maher BS;Maier W;Mallet J;Mattheisen M;Mattingsdal M;McCarley RW;McDonald C;McIntosh AM;Meier S;Meijer CJ;Melle I;Mesholam-Gately RI;Metspalu A;Michie PT;Milani L;Milanova V;Mokrab Y;Morris DW;Müller-Myhsok B;Murphy KC;Murray RM;Myin-Germeys I;Nenadic I;Nertney DA;Nestadt G;Nicodemus KK;Nisenbaum L;Nordin A;O'Callaghan E;O'Dushlaine C;Oh SY;Olincy A;Olsen L;O'Neill FA;Van Os J;Pantelis C;Papadimitriou GN;Parkhomenko E;Pato MT;Paunio T;Psychosis Endophenotypes International Consortium;Perkins DO;Pers TH;Pietiläinen O;Pimm J;Pocklington AJ;Powell J;Price A;Pulver AE;Purcell SM;Quested D;Rasmussen HB;Reichenberg A;Reimers MA;Richards AL;Roffman JL;Roussos P;Ruderfer DM;Salomaa V;Sanders AR;Savitz A;Schall U;Schulze TG;Schwab SG;Scolnick EM;Scott RJ;Seidman LJ;Shi J;Silverman JM;Smoller JW;Söderman E;Spencer CCA;Stahl EA;Strengman E;Strohmaier J;Stroup TS;Suvisaari J;Svrakic DM;Szatkiewicz JP;Thirumalai S;Tooney PA;Veijola J;Visscher PM;Waddington J;Walsh D;Webb BT;Weiser M;Wildenauer DB;Williams NM;Williams S;Witt SH;Wolen AR;Wormley BK;Wray NR;Wu JQ;Zai CC;Adolfsson R;Andreassen OA;Blackwood DHR;Bramon E;Buxbaum JD;Cichon S;Collier DA;Corvin A;Daly MJ;Darvasi A;Domenici E;Esko T;Gejman PV;Gill M;Gurling H;Hultman CM;Iwata N;Jablensky AV;Jönsson EG;Kendler KS;Kirov G;Knight J;Levinson DF;Li QS;McCarroll SA;McQuillin A;Moran JL;Mowry BJ;Nöthen MM;Ophoff RA;Owen MJ;Palotie A;Pato CN;Petryshen TL;Posthuma D;Rietschel M;Riley BP;Rujescu D;Sklar P;St Clair D;Walters JTR;Werge T;Sullivan PF;O'Donovan MC;Scherer SW;Neale BM;Sebat J;CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium
拷贝数变异(CNV)与精神分裂症(SCZ)的遗传病因密切相关。然而，由于样本数量有限，对CNV对风险的贡献的全基因组调查一直受到阻碍。我们试图通过对21,094例病例和20,227例对照的SCZ队列应用集中分析管道来解决这一障碍。3例患者CNV负荷总体丰富(OR=1.11，P=5.7×10−15)，排除既往研究中涉及的基因座(OR=1.0 7，P=1.7×10−6)后，CNV负荷持续增加。与突触功能相关的基因(OR=1.6 8，P=2.8×10−11)和神经行为表型相关基因(OR=1.18，P=7.3×10−5)丰富了新生血管负荷。其中1q21.1、2p16.3(NRXN1)、3q29、7q11.2、15q13.3、16p11.2远端、16p11.2近端和22q11.2等8个基因座在全基因组范围内均有显著的检测结果。另外8个候选易感和保护基因座被发现支持，这些基因座主要由非等位基因同源重组介导的CNV组成。
Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination.
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影响因子：
--
作者：
El-Hattab AW;Schaaf CP;Fang P;Roeder E;Kimonis VE;Church JA;Patel A;Cheung SW
通讯作者：
Cheung SW
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：
30.8
作者：
McCarthy, Shane E.;Makarov, Vladimir;Kirov, George;Addington, Anjene M.;McClellan, Jon;Yoon, Seungtai;Perkins, Diana O.;Dickel, Diane E.;Kusenda, Mary;Krastoshevsky, Olga;Krause, Verena;Kumar, Ravinesh A.;Grozeva, Detelina;Malhotra, Dheeraj;Walsh, Tom;Zackai, Elaine H.;Kaplan, Paige;Ganesh, Jaya;Krantz, Ian D.;Spinner, Nancy B.;Roccanova, Patricia;Bhandari, Abhishek;Pavon, Kevin;Lakshmi, B.;Leotta, Anthony;Kendall, Jude;Lee, Yoon-ha;Vacic, Vladimir;Gary, Sydney;Iakoucheva, Lilia M.;Crow, Timothy J.;Christian, Susan L.;Lieberman, Jeffrey A.;Stroup, T. Scott;Lehtimaki, Terho;Puura, Kaija;Haldeman-Englert, Chad;Pearl, Justin;Goodell, Meredith;Willour, Virginia L.;DeRosse, Pamela;Steele, Jo;Kassem, Layla;Wolff, Jessica;Chitkara, Nisha;McMahon, Francis J.;Malhotra, Anil K.;Potash, James B.;Schulze, Thomas G.;Noethen, Markus M.;Cichon, Sven;Rietschel, Marcella;Leibenluft, Ellen;Kustanovich, Vlad;Lajonchere, Clara M.;Sutcliffe, James S.;Skuse, David;Gill, Michael;Gallagher, Louise;Mendell, Nancy R.;Craddock, Nick;Owen, Michael J.;O'Donovan, Michael C.;Shaikh, Tamim H.;Susser, Ezra;DeLisi, Lynn E.;Sullivan, Patrick F.;Deutsch, Curtis K.;Rapoport, Judith;Levy, Deborah L.;King, Mary-Claire;Sebat, Jonathan
通讯作者：
Sebat, Jonathan
影响因子：
64.8
作者：
Sudmant PH;Rausch T;Gardner EJ;Handsaker RE;Abyzov A;Huddleston J;Zhang Y;Ye K;Jun G;Fritz MH;Konkel MK;Malhotra A;Stütz AM;Shi X;Casale FP;Chen J;Hormozdiari F;Dayama G;Chen K;Malig M;Chaisson MJP;Walter K;Meiers S;Kashin S;Garrison E;Auton A;Lam HYK;Mu XJ;Alkan C;Antaki D;Bae T;Cerveira E;Chines P;Chong Z;Clarke L;Dal E;Ding L;Emery S;Fan X;Gujral M;Kahveci F;Kidd JM;Kong Y;Lameijer EW;McCarthy S;Flicek P;Gibbs RA;Marth G;Mason CE;Menelaou A;Muzny DM;Nelson BJ;Noor A;Parrish NF;Pendleton M;Quitadamo A;Raeder B;Schadt EE;Romanovitch M;Schlattl A;Sebra R;Shabalin AA;Untergasser A;Walker JA;Wang M;Yu F;Zhang C;Zhang J;Zheng-Bradley X;Zhou W;Zichner T;Sebat J;Batzer MA;McCarroll SA;1000 Genomes Project Consortium;Mills RE;Gerstein MB;Bashir A;Stegle O;Devine SE;Lee C;Eichler EE;Korbel JO
通讯作者：
Korbel JO
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.