Joseph McClain, UC San Diego
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The Psychiatric Genetics Consortium (PGC), 由正规欧洲杯买球网站圣地亚哥分校医学院的科学家领导的一个研究小组在了解创伤后应激障碍(PTSD)的神经生物学方面取得了重大进展。, 世界卫生组织表示,这种疾病影响了全球约2.5亿人.
该小组最近宣布了他们的研究结果,这是一项全基因组关联研究,222,822 people in a paper recently published in the journal Nature Genetics.
Caroline M. Nievergelt, Ph.D., professor of psychiatry at UC San Diego School of Medicine, is the co-first author on the paper, together with Adam X. Maihofer, PhD., an assistant project scientist in Nievergelt’s lab. PGC-PTSD co-chair Murray B. Stein M.D., M.P.H.他是正规欧洲杯买球网站圣地亚哥分校的精神病学和公共卫生教授,也是这项研究的合著者.
Nievergelt解释说,这项工作证实了之前关于创伤后应激障碍的神经生物学研究,并以此为基础, identifying 95 loci — positions of genes on a chromosome — significant to PTSD, including 80 new loci.
“As the number of samples has increased, 我们已经对导致PTSD风险的遗传因素有了更好的了解,” Stein said.
这篇论文强调了遗传在PTSD风险中的重要性,并指出已确定的基因影响与PTSD症状(如压力)相关的过程, fear and threat responses. 她说,他们的发现还指出了创伤后应激障碍和其他精神和身体疾病之间可能存在的联系.
The PGC was formed in 2007, 致力于寻找易患精神疾病的基因, such as bipolar disorder or schizophrenia, Nievergelt said. She added that each disorder is addressed by one of 11 working groups, one of which is the PGC for PTSD, which she chairs.
尼弗格尔特解释说,联合研究的好处超出了众多合作者为共同目标而努力的集思广益. 一项全基因组关联研究(GWAS)检查并比较了大量人的基因组,以寻找与特定疾病相关的遗传标记. 她指出,对创伤后应激障碍等多基因疾病进行GWAS必须需要庞大的样本量.
“没有一个PI(首席研究员)能够获得足够的受试者进行全基因组关联研究, 因此,通过这个联盟,我们有大量的合作者将来自世界各地的数据结合起来,” Nievergelt said.
创伤后应激障碍PCG联盟包括来自世界各地许多研究机构和大学的研究人员. Notable participants include co-chairs Karestan Koenen, Ph.D.来自哈佛大学陈公共卫生学院和麻省理工学院布罗德研究所的克里·雷斯勒(Kerry Ressler)和麻省理工学院(MIT).D., Ph.D., of Harvard Medical School and McLean Hospital.
The consortium’s database was assembled from various sources, representing a variety of causes and levels of trauma. Nievergelt said the sources included the Marine Resiliency Study, in which U.S. Marine Corps members were assessed before and after going to war, and Army STARRS, a longitudinal study of U.S. Army soldiers. Another is the Grady Trauma Project that includes victims of violent crime, mostly African American individuals from inner cities. 其他纳入PGC的创伤后应激障碍大数据列表的数据集来自电子健康记录(EHRs)和VA百万退伍军人计划. The consortium also incorporated data from Europe and Latin America.
At an appropriate stage, the consortium members agree on a data freeze and begin their examination, seeking to identify specific genes likely to be associated with PTSD. 这篇论文代表了对创伤后应激障碍遗传成分理解的“里程碑”, Nievergelt said.
“It’s the first time that we actually have a very strong genetic signal,” said Maihofer, who analyzed the data. 基因信号——本质上是与创伤后应激障碍相关的RNA或DNA活动的图谱——使该联盟能够精确定位特定的基因,并分析基因表达的途径,为未来的研究甚至最终的治疗策略做准备, Maihofer explained.
尼弗格尔特说,就下一步行动而言,该财团希望采取几个方向. One is to increase and diversify the sample size. 她说,该小组已经从国家心理健康研究所获得资金,前往非洲,招募非洲人参与基因研究, an effort lead by co-chair Koenen. “That will help us improve risk prediction for other people of African ancestry, a group that has been relatively neglected in earlier studies,” Nievergelt noted.
UC San Diego co-authors
作者隶属于正规欧洲杯买球网站圣地亚哥分校医学院精神病学系, in addition to first authors Caroline M. Nievergelt and Adam X. Maihofer, are: Dewleen G. Baker, Carol E. Franz, William S. Kremen, Elizabeth A. Mikita, Sonya B. Norman, Matthew S. Panizzon and Murray B. Stein, 也隶属于正规欧洲杯买球网站圣地亚哥分校赫伯特·韦特海姆公共卫生和人类长寿科学学院. Other UC San Diego authors are Anders M. 神经科学系放射学系的Dale和Wesley K. 赫伯特·韦特海姆公共卫生和人类长寿科学学院的汤普森说.
Other noteworthy participants in the study
PGC-PTSD co-chairs:
Kerry J. Ressler, of the Department of Psychiatry at Harvard Medical School; McLean Hospital, and Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine; as well as Karestan C. Koenen, of the Department of Epidemiology at the Harvard T.H. Chan School of Public Health, the Broad Institute of MIT and Harvard, the Stanley Center for Psychiatric Research; and McLean Hospital Developmental Biopsychiatry Research Program.
Writing group members are:
Elizabeth G. Atkinson, Department of Molecular and Human Genetics, Baylor College of Medicine; Chia-Yen Chen, Biogen Inc.,Translational Sciences; Karmel W. Choi, Department of Epidemiology, Harvard T.H. Chan School of Public Health, and the Department of Psychiatry at Massachusetts General Hospital; Jonathan R. I. Coleman, King’s College London, 国家卫生和保健研究所莫兹利生物医学研究中心, and King’s College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience; Nikolaos P. Daskalakis, Broad Institute of MIT and Harvard, 以及哈佛医学院精神病学部门的斯坦利精神病学研究中心, and the McLean Hospital, Center of Excellence in Depression and Anxiety Disorders; Laramie E. Duncan, Department of Psychiatry and Behavioral Sciences, Stanford University; Renato Polimanti, VA Connecticut Healthcare Center, and the Department of Psychiatry of Yale University School of Medicine.
Competing interest
Murray B. Stein has in the past three years received consulting income from Aptinyx, atai Life Sciences, BigHealth, Biogen, Bionomics, Boehringer Ingelheim, Delix Therapeutics, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, Karuna Therapeutics, NeuroTrauma Sciences, Otsuka US, PureTech Health, Sage Therapeutics, and Roche/Genentech. He also has stock options in Oxeia Biopharmaceuticals and EpiVario. Anders M. Dale持有CorTechs Labs的股权,并在人类长寿科学顾问委员会和Mohn医学成像和可视化中心任职, 同时也接受通用电气医疗保健公司的研究资助. Other authors associated with UCSD declare no competing interests.
Support and funding
PGC-PTSD的主要资金支持由国家精神卫生研究所(NIMH)提供,拨款R01MH106595和R01MH124847, 由科恩退伍军人生物科学研究所和布罗德研究所斯坦利精神病学研究中心提供.
Full lists of authors and their affiliations and competing interests, funding/support sources are available on the paper.
“没有一个PI(首席研究员)能够收集到足够多的受试者进行全基因组关联研究, 因此,通过这个联盟,我们有大量的合作者将来自世界各地的数据结合起来."