Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders

精神分裂症(面向对象编程) 前额叶皮质 精神科 背景(考古学) 转录组 医学 性别特征 自闭症谱系障碍 自闭症 神经科学 生物 遗传学 基因 基因表达 古生物学 认知
作者
Yan Xia,Xia Chang-bin,Yi Jiang,Yu Chen,Jiaqi Zhou,Rujia Dai,Cong Han,Zhongzheng Mao,Chunyu Liu,Chao Chen,Schahram Akbarian,Alexej Abyzov,Nadav Ahituv,Dhivya Arasappan,José Juan Almagro Armenteros,Brian J. Beliveau,Jaroslav Bendl,Sabina Berretta,Rahul Bharadwaj,Arjun Bhattacharya,Lucy Bicks,Kristen Brennand,Davide Capauto,Frances A. Champagne,Tanima Chatterjee,Chris Chatzinakos,Yuhang Chen,H. Isaac Chen,Yuyan Cheng,Lijun Cheng,Andrew Chess,Jo-fan Chien,Zhiyuan Chu,Declan Clarke,Ashley Clement,Leonardo Collado‐Torres,Gregory M. Cooper,Gregory E. Crawford,Nikolaos P. Daskalakis,José Dávila-Velderrain,Amy Deep‐Soboslay,Chengyu Deng,Christopher P. DiPietro,Stella Dracheva,Shiron Drusinsky,Ziheng Duan,Duc M. Duong,Cagatay Dursun,Nicholas J. Eagles,Jonathan I. Edelstein,Prashant S. Emani,John F. Fullard,Kiki Galani,Timur R. Galeev,Michael J. Gandal,Sophia C. Gaynor,Mark Gerstein,Daniel H. Geschwind,Kiran Girdhar,Fernando S. Goes,William J. Greenleaf,Jennifer Grundman,Hanmin Guo,Qiuyu Guo,Chirag Gupta,Yoav Hadas,Joachim Hallmayer,Xikun Han,Vahram Haroutunian,Natalie Hawken,Chuan He,Ella Henry,Stephanie C. Hicks,Marcus Ho,Li‐Lun Ho,Li‐Lun Ho,Yi‐Ling Huang,Louise A. Huuki-Myers,Ahyeon Hwang,Thomas M. Hyde,Artemis Iatrou,Fumitaka Inoue,Aarti Jajoo,Matthew L. Jensen,Lihua Jiang,Peng Jin,Ting Jin,Connor Jops,Alexandre Jourdon,Riki Kawaguchi,Jiewei Xu,Saniya Khullar,Joel E. Kleinman,Steven P. Kleopoulos,Alexey Kozlenkov,Arnold R. Kriegstein,Anshul Kundaje,Soumya Kundu,Che-Yu Lee,Che-Yu Lee,Junhao Li,Mingfeng Li,Lin Xiao,Shuang Liu,Jason Liu,Shuang Liu,Shuang Liu,Shaoke Lou,Jacob M. Loupe,Dan Lu,Shaojie Ma,Liang Ma,Michael Margolis,Jessica Mariani,Kristen R. Maynard,Kristen R. Maynard,Samantha Mazariegos,Ran Meng,Inez Myin‐Germeys,Courtney Micallef,Tatiana Mikhailova,Guo‐li Ming,Shahin Mohammadi,Emma Monte,Kelsey S. Montgomery,Jill Moore,Jennifer R. Moran,Eran A. Mukamel,Angus C. Nairn,Charles B. Nemeroff,Pengyu Ni,Scott Norton,Tomasz J. Nowakowski,Larsson Omberg,Stephanie C. Page,Saejeong Park,Ashok Patowary,Reenal Pattni,Geo Pertea,Mette A. Peters,Nishigandha Phalke,Dalila Pinto,Milos Pjanic,Sirisha Pochareddy,Katherine S. Pollard,Alex A. Pollen,Henry Pratt,Pawel F. Przytycki,Carolin Purmann,Zhaohui Qin,Pingping Qu,Diana Quintero,Towfique Raj,Ananya S. Rajagopalan,Ananya S. Rajagopalan,Thomas Reimonn,Kerry J. Ressler,D. W. Ross,Panos Roussos,Joel Rozowsky,Megan R. Ruth,W. Brad Ruzicka,Stephan Sanders,J Schneider,Soraya Scuderi,Robert Sebra,Nenad Šestan,Nicholas T. Seyfried,Zhiping Shao,Nicole Shedd,Nicole Shedd,Joo Heon Shin,Mario Škarica,Clara Snijders,Hong-Jun Song,Matthew W. State,Jason L. Stein,Marilyn Steyert,Sivan Subburaju,Thomas C. Südhof,M Snyder,Ran Tao,Karen Therrien,Li‐Huei Tsai,Alexander E. Urban,Flora M. Vaccarino,Harm van Bake,Daniel Vo,Georgios Voloudakis,Brie Wamsley,Tao Wang,Sidney H. Wang,Daifeng Wang,Yifan Wang,Jonathan Warrell,Yu Wei,Annika K. Weimer,Daniel R. Weinberger,Cindy Wen,Zhiping Weng,Sean Whalen,Kevin P. White,A. Jeremy Willsey,Hyejung Won,Wing Kee Wong,Hao Wu,Feinan Wu,Stefan Wuchty,Dennis Wylie,Siwei Xu,Chloe X. Yap,Biao Zeng,Pan Zhang,Chunling Zhang,Bin Zhang,Jing Zhang,Yanqiong Zhang,Xiao Zhou,Ryan Ziffra,Zane Zeier,Trisha M. Zintel
出处
期刊:Science Translational Medicine [American Association for the Advancement of Science (AAAS)]
卷期号:16 (749) 被引量:2
标识
DOI:10.1126/scitranslmed.adh9974
摘要

Many psychiatric disorders exhibit sex differences, but the underlying mechanisms remain poorly understood. We analyzed transcriptomics data from 2160 postmortem adult prefrontal cortex brain samples from the PsychENCODE consortium in a sex-stratified study design. We compared transcriptomics data of postmortem brain samples from patients with schizophrenia (SCZ), bipolar disorder (BD), and autism spectrum disorder (ASD) with transcriptomics data of postmortem control brains from individuals without a known history of psychiatric disease. We found that brain samples from females with SCZ, BD, and ASD showed a higher burden of transcriptomic dysfunction than did brain samples from males with these disorders. This observation was supported by the larger number of differentially expressed genes (DEGs) and a greater magnitude of gene expression changes observed in female versus male brain specimens. In addition, female patient brain samples showed greater overall connectivity dysfunction, defined by a higher proportion of gene coexpression modules with connectivity changes and higher connectivity burden, indicating a greater degree of gene coexpression variability. We identified several gene coexpression modules enriched in sex-biased DEGs and identified genes from a genome-wide association study that were involved in immune and synaptic functions across different brain cell types. We found a number of genes as hubs within these modules, including those encoding
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