학술논문
Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
Document Type
Academic Journal
Author
Gandal, Michael J.; Haney, Jillian R.; Parikshak, Neelroop N.; Leppa, Virpi; Ramaswami, Gokul; Hartl, Chris; Schork, Andrew J.; Appadurai, Vivek; Buil, Alfonso; Werge, Thomas M.; Liu, Chunyu; White, Kevin P.; Horvath, Steve; Geschwind, Daniel H.; Sestan, Nenad; Vaccarino, Flora; Gerstein, Mark; Weissman, Sherman; Pochareddy, Sirisha; State, Matthew; Knowles, James; Farnham, Peggy; Akbarian, Schahram; Pinto, Dalila; Van Baekl, Harm; Dracheva, Stella; Jaffe, Andrew; Hyde, Thomas; Zandi, Peter; Crawford, Gregory; Sullivan, Pat; Thompson, Wesley Kurt; Mortensen, Preben Bo; Agerbo, Esben; Pedersen, Marianne Giørtz; Pedersen, Carsten Bøcker; Mors, Ole; Børglum, Anders D.; Nordentoft, Merete; Hougaard, David M.; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Martin, Alicia R.; Dumont, Ashley; Stevens, Christine; Churchhouse, Claire; Howrigan, Daniel P.; Palmer, Duncan S.; Robinson, Elise B.; Satterstrom, Kyle F.; Cerrato, Felecia; Huang, Hailiang; Goldstein, Jacqueline; Moran, Jennifer; Julian, Joanna Martin; Kimberly, Maller; Patrick, Chambert; Turley, Raymond; Walters, Rich; Belliveau, Stephan; Ripke, Timothy; Poterba, Mark J.; Daly, Benjamin; Neale, Menachem; Fromer, Panos; Roussos, Jessica S.; Johnson, Hardik R.; Shah, Milind C.; Mahajan, Eric; Schadt, Vahram; Haroutunian, Douglas M.; Ruderfer, Joseph D.; Buxbaum, Solveig K.; Sieberts, Kristen; Dang, Ben; Logsdon, Lara M.; Mangravite, Mette; Peters, Raquel E.; Gur, Chang-Gyu; Hahn, Bernie; Devlin, Lambertus L.; Klei, David; Lewis, Barbara; Lipska, Keisuke; Hirai, Hiroyoshi; Toyoshiba, Enrico; Domenici
Source
Science. Feb 09, 2018 359(6376):693-697
Subject
Language
English
ISSN
0036-8075
Abstract
The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders—autism, schizophrenia, bipolar disorder, depression, and alcoholism—compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism–based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.