Implication of a rare deletion at distal 16p11.2 in schizophrenia.
Implication of a rare deletion at distal 16p11.2 in schizophrenia.
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DOI：
10.1001/2013.jamapsychiatry.71
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发表时间：
2013-03
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：
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
大的基因组拷贝数变异（CNVs）被认为是精神分裂症的强危险因素。然而，这些事件的罕见性为鉴定进一步的致病基因座带来了挑战，并且需要非常大的样品来提供令人信服的复制。检测增加精神分裂症易感性的新CNV，利用两个种族同质的发现队列和大样本重复。微阵列数据的遗传关联研究。在不同国家的9个地点收集了DNA样本。两个发现队列包括：a）790例（精神分裂症和情感性精神障碍）和1347名德系犹太血统的对照组;和B）662名来自保加利亚的三人组（患有精神分裂症或情感性精神障碍的后代）。复制数据集包括12，398例病例和17，945例对照。与对照组相比，病例组特异性CNV的发生率在统计学上增加。一个新的基因座被牵连：在远端16p11.2，这并不重叠的近端16p11.2基因座先前报告的精神分裂症和自闭症的缺失。在13，850例病例中发现13例（0.094%）该位点缺失，在19，954例对照中发现3例（0.015%），Fisher精确检验p = 0.0014; OR = 6.25（95%CI = 1.78 - 21.93）。在远端16p11.2的缺失先前已被牵连在发育迟缓和肥胖。该区域包含9个基因，其中几个涉及神经系统疾病，体重调节和葡萄糖稳态。在大约一半的病例中观察到缺失的端粒延伸，但没有对照，可能涉及另外8个基因。我们的研究结果为CNV增加了一个新的位点，增加了患精神分裂症的风险。
Large genomic copy number variations (CNVs) have been implicated as strong risk factors for schizophrenia. However, the rarity of these events has created challenges for the identification of further pathogenic loci, and extremely large samples are required to provide convincing replication. To detect novel CNVs increasing susceptibility to schizophrenia, utilizing two ethnically homogeneous discovery cohorts and replication in large samples. Genetic association study of microarray data. DNA samples were collected at nine sites from different countries. Two discovery cohorts were comprised of: a) 790 cases (schizophrenia and schizoaffective disorder) and 1347 controls of Ashkenazi Jewish descent; and b) 662 trios (offspring affected with schizophrenia or schizoaffective disorder) from Bulgaria. Replication datasets consisted of 12,398 cases and 17,945 controls. Statistically increased rate of specific CNVs in cases versus controls. One novel locus was implicated: a deletion at distal 16p11.2, which does not overlap the proximal 16p11.2 locus previously reported in schizophrenia and autism. Deletions at this locus were found in 13 out of 13,850 cases (0.094%) and in 3 out of 19,954 controls (0.015%), Fisher Exact p = 0.0014; OR = 6.25 (95%CI = 1.78 – 21.93). Deletions at distal 16p11.2 have been previously implicated in developmental delay and obesity. The region contains nine genes, several of which are implicated in neurological diseases, regulation of body weight, and glucose homeostasis. A telomeric extension of the deletion, observed in about half the cases but no controls, potentially implicates an additional eight genes. Our findings add a new locus to the list of CNVs that increase risk to develop 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：
12.3
作者：
Guha, Saurav;Rosenfeld, Jeffrey A.;Lencz, Todd
通讯作者：
Lencz, Todd
影响因子：
8.8
作者：
Bachmann-Gagescu, Ruxandra;Mefford, Heather C.;Tsuchiya, Karen D.
通讯作者：
Tsuchiya, Karen D.
影响因子：
10.3
作者：
Gordon-Smith, K.;Jones, L. A.;Craddock, N.
通讯作者：
Craddock, N.
影响因子：
30.8
作者：
Cooper, Gregory M.;Coe, Bradley P.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.