Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications.
Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications.
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DOI：
10.1176/appi.ajp.2010.10060876
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Gejman PV
中科院分区：
文献类型：
--
作者：
Levinson DF;Duan J;Oh S;Wang K;Sanders AR;Shi J;Zhang N;Mowry BJ;Olincy A;Amin F;Cloninger CR;Silverman JM;Buccola NG;Byerley WF;Black DW;Kendler KS;Freedman R;Dudbridge F;Pe'er I;Hakonarson H;Bergen SE;Fanous AH;Holmans PA;Gejman PV
为了评估先前报道的拷贝数变异（CNVs）与精神分裂症的相关性，并确定其他相关性，作者分析了精神分裂症分子遗传学研究（MGS）中的CNVs和其他可用数据。经过质量控制后，3，945名精神分裂症或情感障碍受试者和3，611名筛选的对照受试者的MGS数据可用于分析罕见CNV（<1%频率）。选择CNV检测阈值，使151次重复测定的一致性最大化。进行了逐点和基因分析，以及对先前报道的区域的分析。对选定区域进行目视检查，并用定量聚合酶链反应进行确认。在MGS数据与其他可用数据集相结合的分析中，观察到先前报道的染色体1q21.1，15q13.3和22q11.21缺失，16p11.2重复和NRXN 1外显子破坏缺失的比值比为7.5或更高。最一致支持的候选关联包括染色体3q 29（21个基因，TFRC到BDH 1）中的1.6 Mb缺失，这是以前在轻度-中度智力低下综合征中描述的，血管活性肠肽受体2（VIPR 2）基因中的外显子重复，以及C16 orf 72中的外显子重复。病例受试者的基因组范围内的基因缺失数量略高（>100 kb和>1 Mb），但没有重复。这些数据有力地证实了精神分裂症与1q21.1、15q13.3和22q11.21缺失、16p11.2重复和外显子NRXN 1缺失的关联。这些CNV，以及3q 29缺失，也与精神发育迟滞，自闭症谱系障碍和癫痫有关。鉴定了包括VIPR 2在内的其他候选基因和区域。对这些联系的潜在机制的研究将有助于阐明精神分裂症的病理生理学。
To evaluate previously reported associations of copy number variants (CNVs) with schizophrenia and to identify additional associations, the authors analyzed CNVs in the Molecular Genetics of Schizophrenia study (MGS) and additional available data. After quality control, MGS data for 3,945 subjects with schizophrenia or schizoaffective disorder and 3,611 screened comparison subjects were available for analysis of rare CNVs (<1% frequency). CNV detection thresholds were chosen that maximized concordance in 151 duplicate assays. Pointwise and gene-wise analyses were carried out, as well as analyses of previously reported regions. Selected regions were visually inspected and confirmed with quantitative polymerase chain reaction. In analyses of MGS data combined with other available data sets, odds ratios of 7.5 or greater were observed for previously reported deletions in chromosomes 1q21.1, 15q13.3, and 22q11.21, duplications in 16p11.2, and exon-disrupting deletions in NRXN1. The most consistently supported candidate associations across data sets included a 1.6-Mb deletion in chromosome 3q29 (21 genes, TFRC to BDH1) that was previously described in a mild-moderate mental retardation syndrome, exonic duplications in the gene for vasoactive intestinal peptide receptor 2 (VIPR2), and exonic duplications in C16orf72. The case subjects had a modestly higher genome-wide number of gene-containing deletions (>100 kb and >1 Mb) but not duplications. The data strongly confirm the association of schizophrenia with 1q21.1, 15q13.3, and 22q11.21 deletions, 16p11.2 duplications, and exonic NRXN1 deletions. These CNVs, as well as 3q29 deletions, are also associated with mental retardation, autism spectrum disorders, and epilepsy. Additional candidate genes and regions, including VIPR2, were identified. Study of the mechanisms underlying these associations should shed light on the pathophysiology of schizophrenia.
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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：
5.2
作者：
Floris, Chiara;Rassu, Stefania;Crisponi, Laura
通讯作者：
Crisponi, Laura
影响因子：
4.4
作者：
Schwarz, Emanuel;Prabakaran, Sudhakaran;Bahn, Sabine
通讯作者：
Bahn, Sabine
影响因子：
11
作者：
Hashimoto, R.;Hashimoto, H.;Baba, A.
通讯作者：
Baba, A.
影响因子：
7
作者：
Shaikh, Tamim H.;Gai, Xiaowu;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon