精神病基因组学联盟多疾病团队揭示了八种不同精神疾病的基因组关系、新型基因座和多效性机制。相关论文2019年12月12日发表在《细胞》上。
研究人员对神经性厌食症、注意力缺陷/多动障碍、自闭症谱系障碍、躁郁症、重度抑郁症、强迫症、精神分裂症和图雷特综合症进行了全基因组研究，对232,964例病例和494,162例对照进行了分析。遗传相关分析揭示了八种疾病中的有意义结构，确定了三组相互关联的疾病。对这八种疾病的荟萃分析检测到109个与至少两种精神疾病有关的基因座，包括23种对四种或FC碰碰胡老虎机法典-提高赢钱机率的下注技巧种疾病具有多效性的基因座和11种对多种疾病具有拮抗作用的基因座。多效性基因座位于这样的基因中，其在整个生命周期中都在大脑中表达增强，从出生前的中期开始就在大脑中表达，并且在神经发育过程中起着重要的作用。这些发现对精神病学，药物开发和风险预测具有重要意义。
据了解，精神疾病的遗传影响超越了诊断界限，这表明贡献位点的实质多效性。但是，这些多效作用的性质和机理仍不清楚。
附：英文原文
Title: Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
Author: Phil H. Lee, Verneri Anttila, Hyejung Won, Yen-Chen A. Feng, Jacob Rosenthal, Zhaozhong Zhu, Elliot M. Tucker-Drob, Michel G. Nivard, Andrew D. Grotzinger, Danielle Posthuma, Meg M.-J. Wang, Dongmei Yu, Eli A. Stahl, Raymond K. Walters, Richard J.L. Anney, Laramie E. Duncan, Tian Ge, Rolf Adolfsson, Tobias Banaschewski, Sintia Belangero, Edwin H. Cook, Giovanni Coppola, Eske M. Derks, Pieter J. Hoekstra, Jaakko Kaprio, Anna Keski-Rahkonen, George Kirov, Henry R. Kranzler, Jurjen J. Luykx, Luis A. Rohde, Clement C. Zai, Esben Agerbo, M.J. Arranz, Philip Asherson, Marie Bkvad-Hansen, Gísli Baldursson, Mark Bellgrove, Richard A. Belliveau, Jan Buitelaar, Christie L. Burton, Jonas Bybjerg-Grauholm, Miquel Casas, Felecia Cerrato, Kimberly Chambert, Claire Churchhouse, Bru Cormand, Jennifer Crosbie, Sren Dalsgaard, Ditte Demontis, Alysa E. Doyle, Ashley Dumont, Josephine Elia, Jakob Grove, Olafur O. Gudmundsson, Jan Haavik, Hakon Hakonarson, Christine S. Hansen, Catharina A. Hartman, Ziarih Hawi, Amaia Hervás, David M. Hougaard, Daniel P. Howrigan, Hailiang Huang, Jonna Kuntsi, Kate Langley, Klaus-Peter Lesch, Patrick W.L. Leung, Sandra K. Loo, Joanna Martin, Alicia R. Martin, James J. McGough, Sarah E. Medland, Jennifer L. Moran, Ole Mors, Preben B. Mortensen, Robert D. Oades, Duncan S. Palmer, Carsten B. Pedersen, Marianne G. Pedersen, Triinu Peters, Timothy Poterba, Jesper B. Poulsen, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Aribert Rothenberger, Paula Rovira, Cristina Sánchez-Mora, F. Kyle Satterstrom, Russell Schachar, Maria Soler Artigas, Stacy Steinberg, Hreinn Stefansson, Patrick Turley, G. Bragi Walters, Thomas Werge, Tetyana Zayats, Dan E. Arking, Francesco Bettella, Joseph D. Buxbaum, Jane H. Christensen, Ryan L. Collins, Hilary Coon, Silvia De Rubeis, Richard Delorme, Dorothy E. Grice, Thomas F. Hansen, Peter A. Holmans, Sigrun Hope, Christina M. Hultman, Lambertus Klei, Christine Ladd-Acosta, Pall Magnusson, Terje Nrland, Mette Nyegaard, Dalila Pinto, Per Qvist, Karola Rehnstrm, Abraham Reichenberg, Jennifer Reichert, Kathryn Roeder, Guy A. Rouleau, Evald Saemundsen, Stephan J. Sanders, Sven Sandin, Beate St Pourcain, Kari Stefansson, James S. Sutcliffe, Michael E. Talkowski, Lauren A. Weiss, A. Jeremy Willsey, Ingrid Agartz, Huda Akil, Diego Albani, Martin Alda, Thomas D. Als, Adebayo Anjorin, Lena Backlund, Nicholas Bass, Michael Bauer, Bernhard T. Baune, Frank Bellivier, Sarah E. Bergen, Wade H. Berrettini, Joanna M. Biernacka, Douglas H.R. Blackwood, Erlend Ben, Monika Budde, William Bunney, Margit Burmeister
Issue&Volume: 2019/12/12
Abstract: Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggestingsubstantial pleiotropy of contributing loci. However, the nature and mechanisms ofthese pleiotropic effects remain unclear. We performed analyses of 232,964 cases and494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivitydisorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsivedisorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealeda meaningful structure within the eight disorders, identifying three groups of inter-relateddisorders. Meta-analysis across these eight disorders detected 109 loci associatedwith at least two psychiatric disorders, including 23 loci with pleiotropic effectson four or more disorders and 11 loci with antagonistic effects on multiple disorders.The pleiotropic loci are located within genes that show heightened expression in the brainthroughout the lifespan, beginning prenatally in the second trimester, and play prominentroles in neurodevelopmental processes. These findings have important implicationsfor psychiatric nosology, drug development, and risk prediction.
DOI: 10.1016/j.cell.2019.11.020
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31276-0