Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap | Zendy

Michael J. Gandal | Zendy; Jillian R. Haney | Zendy; Neelroop Parikshak | Zendy; Virpi Leppä | Zendy; Gokul Ramaswami | Zendy; Christopher Hartl | Zendy; Andrew J. Schork | Zendy; Vivek Appadurai | Zendy; Alfonso Buil | Zendy; Thomas Werge | Zendy; Chunyu Liu | Zendy; Kevin P. White | Zendy; Steve Horvath | Zendy; Daniel H. Geschwind | Zendy; Nenad Šestan | Zendy; Flora M. Vaccarino | Zendy; Mark Gerstein | Zendy; Sherman M. Weissman | Zendy; Sirisha Pochareddy | Zendy; Matthew W. State | Zendy; James A. Knowles | Zendy; Peggy Farnham | Zendy; Schahram Akbarian | Zendy; Dalila Pinto | Zendy; Harm Van Baekl | Zendy; Stella Dracheva | Zendy; Andrew E. Jaffe | Zendy; Thomas M. Hyde | Zendy; Peter P. Zandi | Zendy; Gregory E. Crawford | Zendy; Pat Sullivan | Zendy; Wesley K. Thompson | Zendy; Preben Bo Mortensen | Zendy; Esben Agerbo | Zendy; Marianne Giørtz Pedersen | Zendy; Carsten Bøcker Pedersen | Zendy; Ole Mors | Zendy; Anders D. Børglum | Zendy; Merete Nordentoft | Zendy; David M. Hougaard | Zendy; Jonas BybjergGrauholm | Zendy; Marie BækvadHansen | Zendy; Alicia R. Martin | Zendy; Ashley Dumont | Zendy; Christine Stevens | Zendy; Tracy Air | Zendy; Daniel P. Howrigan | Zendy; Duncan S. Palmer | Zendy; Elise Robinson | Zendy; Kyle F. Satterstrom | Zendy; Felecia Cerrato | Zendy; Hailiang Huang | Zendy; Jacqueline I. Goldstein | Zendy; Jennifer L. Moran | Zendy; Joanna Martin Julian | Zendy; M. Alonge Kimberly | Zendy; C. Seed Patrick | Zendy; Patrick Turley | Zendy; Raymond K. Walters | Zendy; Rich Belliveau | Zendy; Stephan Ripke | Zendy; Timothy Poterba | Zendy; Mark J. Daly | Zendy; Benjamin M. Neale | Zendy; Menachem Fromer | Zendy; Panos Roussos | Zendy; Jessica Johnson | Zendy; Hardik Shah | Zendy; Milind Mahajan | Zendy; Eric E. Schadt | Zendy; Vahram Haroutunian | Zendy; Douglas M. Ruderfer | Zendy; Joseph D. Buxbaum | Zendy; Solveig K. Sieberts | Zendy; Kristen K. Dang | Zendy; Ben Logsdon | Zendy; Lara M. Mangravite | Zendy; Mette A. Peters | Zendy; Raquel E. Gur | Zendy; Chang-Gyu Hahn | Zendy; Bernie Devlin | Zendy; Lambertus Klei | Zendy; David A. Lewis | Zendy; Barbara K. Lipska | Zendy; Keisuke Hirai | Zendy; Hiroyoshi Toyoshiba | Zendy; Enrico Domenici | Zendy

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Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap

Author(s) -

Michael J. Gandal,

Jillian R. Haney,

Neelroop Parikshak,

Virpi Leppä,

Gokul Ramaswami,

Christopher Hartl,

Andrew J. Schork,

Vivek Appadurai,

Alfonso Buil,

Thomas Werge,

Chunyu Liu,

Kevin P. White,

Steve Horvath,

Daniel H. Geschwind,

Nenad Šestan,

Flora M. Vaccarino,

Mark Gerstein,

Sherman M. Weissman,

Sirisha Pochareddy,

Matthew W. State,

James A. Knowles,

Peggy Farnham,

Schahram Akbarian,

Dalila Pinto,

Harm Van Baekl,

Stella Dracheva,

Andrew E. Jaffe,

Thomas M. Hyde,

Peter P. Zandi,

Gregory E. Crawford,

Pat Sullivan,

Wesley K. Thompson,

Preben Bo Mortensen,

Esben Agerbo,

Marianne Giørtz Pedersen,

Carsten Bøcker Pedersen,

Ole Mors,

Anders D. Børglum,

Merete Nordentoft,

David M. Hougaard,

Jonas BybjergGrauholm,

Marie BækvadHansen,

Alicia R. Martin,

Ashley Dumont,

Christine Stevens,

Tracy Air,

Daniel P. Howrigan,

Duncan S. Palmer,

Elise Robinson,

Kyle F. Satterstrom,

Felecia Cerrato,

Hailiang Huang,

Jacqueline I. Goldstein,

Jennifer L. Moran,

Joanna Martin Julian,

M. Alonge Kimberly,

C. Seed Patrick,

Patrick Turley,

Raymond K. Walters,

Rich Belliveau,

Stephan Ripke,

Timothy Poterba,

Mark J. Daly,

Benjamin M. Neale,

Menachem Fromer,

Panos Roussos,

Jessica Johnson,

Hardik Shah,

Milind Mahajan,

Eric E. Schadt,

Vahram Haroutunian,

Douglas M. Ruderfer,

Joseph D. Buxbaum,

Solveig K. Sieberts,

Kristen K. Dang,

Ben Logsdon,

Lara M. Mangravite,

Mette A. Peters,

Raquel E. Gur,

Chang-Gyu Hahn,

Bernie Devlin,

Lambertus Klei,

David A. Lewis,

Barbara K. Lipska,

Keisuke Hirai,

Hiroyoshi Toyoshiba,

Enrico Domenici

Publication year - 2018

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aad6469

Subject(s) - neuropathology , psychiatric genetics , transcriptome , gene , disease , psychiatry , genome wide association study , genetics , biology , medicine , schizophrenia (object oriented programming) , gene expression , single nucleotide polymorphism , pathology , genotype

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.

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