Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders
Authors: Yan Xia, Cuihua Xia, Yi Jiang, Yu Chen, Jiaqi Zhou, Rujia Dai, Cong Han, Zhongzheng Mao, Chunyu Liu, Chao Chen, Schahram Akbarian, Alexej Abyzov, Nadav Ahituv, Dhivya Arasappan, Jose Juan Almagro Armenteros, Brian J. Beliveau, Jaroslav Bendl, Sabina Berretta, Rahul A. 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, Jose Davila-Velderrain, Amy Deep-Soboslay, Chengyu Deng, Christopher P. DiPietro, Stella Dracheva, Shiron Drusinsky, Ziheng Duan, Duc Duong, Cagatay Dursun, Nicholas J. Eagles, Jonathan Edelstein, Prashant S. Emani, John F. Fullard, Kiki Galani, Timur Galeev, Michael J. Gandal, Sophia Gaynor, Mark Gerstein, Daniel H. Geschwind, Kiran Girdhar, Fernando S. Goes, William 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, Gabriel E. Hoffman, Yiling Huang, Louise A. Huuki-Myers, Ahyeon Hwang, Thomas M. Hyde, Artemis Iatrou, Fumitaka Inoue, Aarti Jajoo, Matthew Jensen, Lihua Jiang, Peng Jin, Ting Jin, Connor Jops, Alexandre Jourdon, Riki Kawaguchi, Manolis Kellis, Saniya Khullar, Joel E. Kleinman, Steven P. Kleopoulos, Alex Kozlenkov, Arnold Kriegstein, Anshul Kundaje, Soumya Kundu, Cheyu Lee, Donghoon Lee, Junhao Li, Mingfeng Li, Xiao Lin, Shuang Liu, Jason Liu, Jianyin Liu, Shuang Liu, Shaoke Lou, Jacob M. Loupe, Dan Lu, Shaojie Ma, Liang Ma, Michael Margolis, Jessica Mariani, Keri Martinowich, Kristen R. Maynard, Samantha Mazariegos, Ran Meng, Richard M. Myers, Courtney Micallef, Tatiana Mikhailova, Guo-li Ming, Shahin Mohammadi, Emma Monte, Kelsey S. Montgomery, Jill E. Moore, Jennifer R. Moran, Eran A. Mukamel, Angus C. Nairn, Charles B. Nemeroff, Pengyu Ni, Scott Norton, Tomasz 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 Pollen, Henry Pratt, Pawel F. Przytycki, Carolin Purmann, Zhaohui S. Qin, Ping-Ping Qu, Diana Quintero, Towfique Raj, Ananya S. Rajagopalan, Sarah Reach, Thomas Reimonn, Kerry J. Ressler, Deanna Ross, Panos Roussos, Joel Rozowsky, Misir Ruth, W. Brad Ruzicka, Stephan J. Sanders, Juliane M. Schneider, Soraya Scuderi, Robert Sebra, Nenad Sestan, Nicholas Seyfried, Zhiping Shao, Nicole Shedd, Annie W. Shieh, Joo Heon Shin, Mario Skarica, Clara Snijders, Hongjun Song, Matthew W. State, Jason Stein, Marilyn Steyert, Sivan Subburaju, Thomas Sudhof, Michael 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 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 R. Zeier, Trisha M. Zintel
Journal: Science Translational Medicine (2024)

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