研究揭示多種精神疾病的基因組關係、新基因座和多效性機制
作者：
小柯機器人發布時間：2019/12/14 21:41:33
精神病基因組學聯盟多疾病團隊揭示了八種不同精神疾病的基因組關係、新型基因座和多效性機制。相關論文2019年12月12日發表在《細胞》上。
研究人員對神經性厭食症、注意力缺陷/多動障礙、自閉症譜系障礙、躁鬱症、重度抑鬱症、強迫症、精神分裂症和圖雷特綜合症進行了全基因組研究，對232,964例病例和494,162例對照進行了分析。遺傳相關分析揭示了八種疾病中的有意義結構，確定了三組相互關聯的疾病。對這八種疾病的薈萃分析檢測到109個與至少兩種精神疾病有關的基因座，包括23種對四種或更多種疾病具有多效性的基因座和11種對多種疾病具有拮抗作用的基因座。多效性基因座位於這樣的基因中，其在整個生命周期中都在大腦中表達增強，從出生前的中期開始就在大腦中表達，並且在神經發育過程中起著重要的作用。這些發現對精神病學，藥物開發和風險預測具有重要意義。
據了解，精神疾病的遺傳影響超越了診斷界限，這表明貢獻位點的實質多效性。但是，這些多效作用的性質和機理仍不清楚。
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
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