Analysis of copy number variations at 15 schizophrenia-associated loci.
Analysis of copy number variations at 15 schizophrenia-associated loci.
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DOI：
10.1192/bjp.bp.113.131052
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Kirov G
中科院分区：
文献类型：
--
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
背景许多拷贝数变异体（CNVs）被认为是精神分裂症的易感因素。对于其中一些数据仍然模棱两可，精神分裂症患者的频率是不确定的。目的：（a）使用精神分裂症患者（n = 6882）和对照组（n = 6316）的大型新数据集，并（B）结合我们的结果与以前的研究，以确定15个精神分裂症相关基因座的CNV的贡献。方法我们使用Illumina微阵列分析我们的数据。分析仅限于520 766探针共同使用的所有阵列在不同的数据集。结果我们发现，在15个先前涉及的CNVs中，有13个在精神分裂症患者中的发生率高于对照组。在这个新的数据集中，6个名义上显著相关（P<0.05）：1q21.1，NRXN 1，15q11.2和22q11.2的缺失和16p11.2的重复和Angelman/Prader-Willi综合征（AS/PWS）区域。所有8例AS/PWS重复患者均为母体来源。结合已发表的资料，15个位点中有11个位点与精神分裂症有高度显著性关联（P<4.1×10-4）。结论我们加强了对精神分裂症中大多数先前涉及的CNVs的支持。大约2.5%的精神分裂症患者和0.9%的对照者在这些位点之一携带大的、可检测的CNV。常规CNV筛查在临床上可能是合适的，因为已知的有害突变在疾病中的发生率很高，并且与这些可遗传突变相关。
Background A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain. Aims To determine the contribution of CNVs at 15 schizophrenia-associated loci (a) using a large new data-set of patients with schizophrenia (n = 6882) and controls (n = 6316), and (b) combining our results with those from previous studies. Method We used Illumina microarrays to analyse our data. Analyses were restricted to 520 766 probes common to all arrays used in the different data-sets. Results We found higher rates in participants with schizophrenia than in controls for 13 of the 15 previously implicated CNVs. Six were nominally significantly associated (P<0.05) in this new data-set: deletions at 1q21.1, NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader-Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of maternal origin. When combined with published data, 11 of the 15 loci showed highly significant evidence for association with schizophrenia (P<4.1×10–4). Conclusions We strengthen the support for the majority of the previously implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV screening may be clinically appropriate given the high rate of known deleterious mutations in the disorder and the comorbidity associated with these heritable mutations.
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影响因子：
25.8
作者：
Guha, Saurav;Rees, Elliott;Darvasi, Ariel;Ivanov, Dobril;Ikeda, Masashi;Bergen, Sarah E.;Magnusson, Patrik K.;Cormican, Paul;Morris, Derek;Gill, Michael;Cichon, Sven;Rosenfeld, Jeffrey A.;Lee, Annette;Gregersen, Peter K.;Kane, John M.;Malhotra, Anil K.;Rietschel, Marcella;Noethen, Markus M.;Degenhardt, Franziska;Priebe, Lutz;Breuer, Rene;Strohmaier, Jana;Ruderfer, Douglas M.;Moran, Jennifer L.;Chambert, Kimberly D.;Sanders, Alan R.;Shi, Jianxin;Kendler, Kenneth;Riley, Brien;O'Neill, Tony;Walsh, Dermot;Malhotra, Dheeraj;Corvin, Aiden;Purcell, Shaun;Sklar, Pamela;Iwata, Nakao;Hultman, Christina M.;Sullivan, Patrick F.;Sebat, Jonathan;McCarthy, Shane;Gejman, Pablo V.;Levinson, Douglas F.;Owen, Michael J.;O'Donovan, Michael C.;Lencz, Todd;Kirov, George
通讯作者：
Kirov, George
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：
11
作者：
通讯作者：
--
影响因子：
3.5
作者：
Dibbens, Leanne M.;Mullen, Saul;Berkovic, Samuel F.
通讯作者：
Berkovic, Samuel F.
影响因子：
8.8
作者：
Bachmann-Gagescu, Ruxandra;Mefford, Heather C.;Tsuchiya, Karen D.
通讯作者：
Tsuchiya, Karen D.