Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia.
Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia.
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DOI：
10.1016/j.biopsych.2013.05.040
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发表时间：
2014-03-01
影响因子：
10.6
通讯作者：
Warren, Stephen T.
中科院分区：
文献类型：
--
作者：
Mulle, Jennifer Gladys;Pulver, Ann E.;McGrath, John A.;Wolyniec, Paula S.;Dodd, Anne F.;Cutler, David J.;Sebat, Jonathan;Malhotra, Dheeraj;Nestadt, Gerald;Conrad, Donald F.;Hurles, Matthew;Barnes, Chris P.;Ikeda, Masashi;Iwata, Nakao;Levinson, Douglas F.;Gejman, Pablo V.;Sanders, Alan R.;Duan, Jubao;Mitchell, Adele A.;Peter, Inga;Sklar, Pamela;O'Dushlaine, Colm T.;Grozeva, Detelina;O'Donovan, Michael C.;Owen, Michael J.;Hultman, Christina M.;Kahler, Anna K.;Sullivan, Patrick F.;Kirov, George;Warren, Stephen T.
关键词：
几种拷贝数变异（CNV）已被认为是精神分裂症（SZ）的易感因素。这些相同的CNV中的一些也增加了自闭症谱系障碍（ASD）的风险，表明这些疾病之间的病因重叠。最近，染色体7q11.23区域的从头重复与ASD相关。该区域的相互缺失导致Williams-Beuren综合征（WBS）。我们使用高密度全基因组阵列分析了554例SZ病例和1014例对照的德系犹太人队列的拷贝数变异（CNV）。观察到大量罕见和新生CNV，包括在两名无关患者中鉴定的染色体7q11.23上的1.4 Mb重复。为了测试这种7q11.23重复是否也与SZ相关，我们从另外7项高分辨率全基因组CNV检测的研究中获得了14，387例SZ病例和28，139例对照的数据。我们进行了一项荟萃分析，校正研究人群的起源，以评估7q11.23重复是否与SZ相关。我们发现14，387例SZ病例中有11例在7q11.23处重复，而28，139例对照中只有1例重复（未校正比值比，21.52，95%CI：3.13-922.6，p值5.5×10-5;校正比值比10.8，95%CI：1.46-79.62，p值0.007）。三个SZ重复载体与可用的详细回顾性数据，都表现出社交焦虑和语言延迟发病前SZ发病，符合人类研究和动物模型的7q11.23重复。我们已经确定了一个新的CNV与SZ。染色体7q11.23处威廉姆斯综合征缺失的相互重复使SZ的风险增加约10倍。
Several copy number variants (CNVs) have been implicated as susceptibility factors for schizophrenia (SZ). Some of these same CNV also increase risk for autism spectrum disorders (ASD), suggesting an etiologic overlap between these conditions. Recently, de novo duplications of a region on chromosome 7q11.23 were associated with ASD. The reciprocal deletion of this region causes Williams-Beuren syndrome (WBS). We assayed an Ashkenazi Jewish cohort of 554 SZ cases and 1014 controls for copy number variation (CNV), using a high-density genome-wide array. An excess of large rare and de novo CNV were observed, including a 1.4 Mb duplication on chromosome 7q11.23 identified in two unrelated patients. To test whether this 7q11.23 duplication is also associated with SZ, we obtained data for 14,387 SZ cases and 28,139 controls from seven additional studies with high-resolution genome-wide CNV detection. We performed a meta-analysis, correcting for study population of origin, to assess whether the 7q11.23 duplication is associated with SZ. We find duplications at 7q11.23 in 11 of 14,387 SZ cases with only 1 in 28,139 controls (unadjusted odds ratio, 21.52, 95% CI: 3.13-922.6, p-value 5.5×10-5; adjusted odds ratio 10.8, 95% CI: 1.46-79.62, p-value 0.007). Of three SZ duplication carriers with available detailed retrospective data, all show social anxiety and language delay premorbid to SZ onset, consistent with both human studies and animal models of the 7q11.23 duplication. We have identified a new CNV associated with SZ. Reciprocal duplication of the Williams syndrome deletion at chromosome 7q11.23 confers an approximately 10-fold increase in risk for SZ.
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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：
11
作者：
Bergen, S. E.;O'Dushlaine, C. T.;Ripke, S.;Lee, P. H.;Ruderfer, D. M.;Akterin, S.;Moran, J. L.;Chambert, K. D.;Handsaker, R. E.;Backlund, L.;Osby, U.;McCarroll, S.;Landen, M.;Scolnick, E. M.;Magnusson, P. K. E.;Lichtenstein, P.;Hultman, C. M.;Purcell, S. M.;Sklar, P.;Sullivan, P. F.
通讯作者：
Sullivan, P. F.
影响因子：
9.8
作者：
Moreno-De-Luca, Daniel;Mulle, Jennifer G.;Ledbetter, David H.
通讯作者：
Ledbetter, David H.
DOI：
10.1097/gim.0b013e31822c79f9
发表时间：
2011-09
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Kaminsky EB;Kaul V;Paschall J;Church DM;Bunke B;Kunig D;Moreno-De-Luca D;Moreno-De-Luca A;Mulle JG;Warren ST;Richard G;Compton JG;Fuller AE;Gliem TJ;Huang S;Collinson MN;Beal SJ;Ackley T;Pickering DL;Golden DM;Aston E;Whitby H;Shetty S;Rossi MR;Rudd MK;South ST;Brothman AR;Sanger WG;Iyer RK;Crolla JA;Thorland EC;Aradhya S;Ledbetter DH;Martin CL
通讯作者：
Martin CL
影响因子：
9.8
作者：
Mefford, Heather C.;Clauin, Severine;Bellanne-Chantelot, Christine
通讯作者：
Bellanne-Chantelot, Christine