Microduplications of 16p11.2 are associated with schizophrenia.
Microduplications of 16p11.2 are associated with schizophrenia.
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DOI：
10.1038/ng.474
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发表时间：
2009-11
期刊：
影响因子：
30.8
通讯作者：
Sebat, Jonathan
中科院分区：
文献类型：
--
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
16号染色体p11.2区域一个600kb的基因组区域反复出现的微缺失和微重复与儿童期发病的发育障碍有关。在此我们报道在两个大型队列中16p11.2微重复与精神分裂症有很强的关联。在主要样本中，在1906例中有12例（0.63%）以及3971例对照中有1例（0.03%）检测到微重复（P = 1.2×10⁻⁵，优势比 = 25.8）。在重复样本中，在2645例中有9例（0.34%）以及2420例对照中有1例（0.04%）检测到微重复（P = 0.022，优势比 = 8.3）。综合这两个系列，16p11.2微重复使精神分裂症的风险增加14.5倍（95%置信区间[3.3, 62]）。对多种精神疾病的荟萃分析显示微重复与精神分裂症、双相情感障碍和自闭症有显著关联。与之对应的微缺失仅与自闭症和发育障碍有关。对患者临床数据的分析表明，与微重复患者相比，微缺失患者的头围明显更大（P = 0.0007）。我们的研究结果表明16p11.2微重复使精神分裂症和其他精神疾病的风险大幅增加，而与之对应的微缺失则与相反的临床特征有关。
Recurrent microdeletions and microduplications of a 600 kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. Here we report the strong association of 16p11.2 microduplications with schizophrenia in two large cohorts. In the primary sample, the microduplication was detected in 12/1906 (0.63%) cases and 1/3971 (0.03%) controls (P=1.2×10-5, OR=25.8). In the replication sample, the microduplication was detected in 9/2645 (0.34%) cases and 1/2420 (0.04%) controls (P=0.022, OR=8.3). For the series combined, microduplication of 16p11.2 was associated with 14.5-fold increased risk of schizophrenia (95% C.I. [3.3, 62]). A meta-analysis of multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder and autism. The reciprocal microdeletion was associated only with autism and developmental disorders. Analysis of patient clinical data showed that head circumference was significantly larger in patients with the microdeletion compared with patients with the microduplication (P = 0.0007). Our results suggest that the microduplication of 16p11.2 confers substantial risk for schizophrenia and other psychiatric disorders, whereas the reciprocal microdeletion is associated with contrasting clinical features.
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