Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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31835028
TITLE
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders.
ABSTRACT
Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
Copyright 2019 Elsevier Inc. All rights reserved.
DATE PUBLISHED
2019 Dec 12
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2019/01/21
revised 2019/08/01
accepted 2019/11/14
entrez 2019/12/14 06:00
pubmed 2019/12/14 06:00
medline 2019/12/14 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu
Cross-Disorder Group of the Psychiatric Genomics Consortium
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Lee Phil H PH
Anttila Verneri V
Won Hyejung H
Feng Yen-Chen A YA
Rosenthal Jacob J
Zhu Zhaozhong Z
Tucker-Drob Elliot M EM
Nivard Michel G MG
Grotzinger Andrew D AD
Posthuma Danielle D
Wang Meg M-J MM
Yu Dongmei D
Stahl Eli A EA
Walters Raymond K RK
Anney Richard J L RJL
Duncan Laramie E LE
Ge Tian T
Adolfsson Rolf R
Banaschewski Tobias T
Belangero Sintia S
Cook Edwin H EH
Coppola Giovanni G
Derks Eske M EM
Hoekstra Pieter J PJ
Kaprio Jaakko J
Keski-Rahkonen Anna A
Kirov George G
Kranzler Henry R HR
Luykx Jurjen J JJ
Rohde Luis A LA
Zai Clement C CC
Agerbo Esben E
Arranz M J MJ
Asherson Philip P
Bækvad-Hansen Marie M
Baldursson Gísli G
Bellgrove Mark M
Belliveau Richard A RA
Buitelaar Jan J
Burton Christie L CL
Bybjerg-Grauholm Jonas J
Casas Miquel M
Cerrato Felecia F
Chambert Kimberly K
Churchhouse Claire C
Cormand Bru B
Crosbie Jennifer J
Dalsgaard Søren S
Demontis Ditte D
Doyle Alysa E AE
Dumont Ashley A
Elia Josephine J
Grove Jakob J
Gudmundsson Olafur O OO
Haavik Jan J
Hakonarson Hakon H
Hansen Christine S CS
Hartman Catharina A CA
Hawi Ziarih Z
Hervás Amaia A
Hougaard David M DM
Howrigan Daniel P DP
Huang Hailiang H
Kuntsi Jonna J
Langley Kate K
Lesch Klaus-Peter KP
Leung Patrick W L PWL
Loo Sandra K SK
Martin Joanna J
Martin Alicia R AR
McGough James J JJ
Medland Sarah E SE
Moran Jennifer L JL
Mors Ole O
Mortensen Preben B PB
Oades Robert D RD
Palmer Duncan S DS
Pedersen Carsten B CB
Pedersen Marianne G MG
Peters Triinu T
Poterba Timothy T
Poulsen Jesper B JB
Ramos-Quiroga Josep Antoni JA
Reif Andreas A
Ribasés Marta M
Rothenberger Aribert A
Rovira Paula P
Sánchez-Mora Cristina C
Satterstrom F Kyle FK
Schachar Russell R
Artigas Maria Soler MS
Steinberg Stacy S
Stefansson Hreinn H
Turley Patrick P
Walters G Bragi GB
Werge Thomas T
Zayats Tetyana T
Arking Dan E DE
Bettella Francesco F
Buxbaum Joseph D JD
Christensen Jane H JH
Collins Ryan L RL
Coon Hilary H
De Rubeis Silvia S
Delorme Richard R
Grice Dorothy E DE
Hansen Thomas F TF
Holmans Peter A PA
Hope Sigrun S
Hultman Christina M CM
Klei Lambertus L
Ladd-Acosta Christine C
Magnusson Pall P
Nærland Terje T
Nyegaard Mette M
Pinto Dalila D
Qvist Per P
Rehnström Karola K
Reichenberg Abraham A
Reichert Jennifer J
Roeder Kathryn K
Rouleau Guy A GA
Saemundsen Evald E
Sanders Stephan J SJ
Sandin Sven S
St Pourcain Beate B
Stefansson Kari K
Sutcliffe James S JS
Talkowski Michael E ME
Weiss Lauren A LA
Willsey A Jeremy AJ
Agartz Ingrid I
Akil Huda H
Albani Diego D
Alda Martin M
Als Thomas D TD
Anjorin Adebayo A
Backlund Lena L
Bass Nicholas N
Bauer Michael M
Baune Bernhard T BT
Bellivier Frank F
Bergen Sarah E SE
Berrettini Wade H WH
Biernacka Joanna M JM
Blackwood Douglas H R DHR
Bøen Erlend E
Budde Monika M
Bunney William W
Burmeister Margit M
Byerley William W
Byrne Enda M EM
Cichon Sven S
Clarke Toni-Kim TK
Coleman Jonathan R I JRI
Craddock Nicholas N
Curtis David D
Czerski Piotr M PM
Dale Anders M AM
Dalkner Nina N
Dannlowski Udo U
Degenhardt Franziska F
Di Florio Arianna A
Elvsåshagen Torbjørn T
Etain Bruno B
Fischer Sascha B SB
Forstner Andreas J AJ
Forty Liz L
Frank Josef J
Frye Mark M
Fullerton Janice M JM
Gade Katrin K
Gaspar Héléna A HA
Gershon Elliot S ES
Gill Michael M
Goes Fernando S FS
Gordon Scott D SD
Gordon-Smith Katherine K
Green Melissa J MJ
Greenwood Tiffany A TA
Grigoroiu-Serbanescu Maria M
Guzman-Parra José J
Hauser Joanna J
Hautzinger Martin M
Heilbronner Urs U
Herms Stefan S
Hoffmann Per P
Holland Dominic D
Jamain Stéphane S
Jones Ian I
Jones Lisa A LA
Kandaswamy Radhika R
Kelsoe John R JR
Kennedy James L JL
Joachim Oedegaard Ketil OK
Kittel-Schneider Sarah S
Kogevinas Manolis M
Koller Anna C AC
Lavebratt Catharina C
Lewis Cathryn M CM
Li Qingqin S QS
Lissowska Jolanta J
Loohuis Loes M O LMO
Lucae Susanne S
Maaser Anna A
Malt Ulrik F UF
Martin Nicholas G NG
Martinsson Lina L
McElroy Susan L SL
McMahon Francis J FJ
McQuillin Andrew A
Melle Ingrid I
Metspalu Andres A
Millischer Vincent V
Mitchell Philip B PB
Montgomery Grant W GW
Morken Gunnar G
Morris Derek W DW
Müller-Myhsok Bertram B
Mullins Niamh N
Myers Richard M RM
Nievergelt Caroline M CM
Nordentoft Merete M
Adolfsson Annelie Nordin AN
Nöthen Markus M MM
Ophoff Roel A RA
Owen Michael J MJ
Paciga Sara A SA
Pato Carlos N CN
Pato Michele T MT
Perlis Roy H RH
Perry Amy A
Potash James B JB
Reinbold Céline S CS
Rietschel Marcella M
Rivera Margarita M
Roberson Mary M
Schalling Martin M
Schofield Peter R PR
Schulze Thomas G TG
Scott Laura J LJ
Serretti Alessandro A
Sigurdsson Engilbert E
Smeland Olav B OB
Stordal Eystein E
Streit Fabian F
Strohmaier Jana J
Thorgeirsson Thorgeir E TE
Treutlein Jens J
Turecki Gustavo G
Vaaler Arne E AE
Vieta Eduard E
Vincent John B JB
Wang Yunpeng Y
Witt Stephanie H SH
Zandi Peter P
Adan Roger A H RAH
Alfredsson Lars L
Ando Tetsuya T
Aschauer Harald H
Baker Jessica H JH
Bencko Vladimir V
Bergen Andrew W AW
Birgegård Andreas A
Perica Vesna Boraska VB
Brandt Harry H
Burghardt Roland R
Carlberg Laura L
Cassina Matteo M
Clementi Maurizio M
Courtet Philippe P
Crawford Steven S
Crow Scott S
Crowley James J JJ
Danner Unna N UN
Davis Oliver S P OSP
Degortes Daniela D
DeSocio Janiece E JE
Dick Danielle M DM
Dina Christian C
Docampo Elisa E
Egberts Karin K
Ehrlich Stefan S
Espeseth Thomas T
Fernández-Aranda Fernando F
Fichter Manfred M MM
Foretova Lenka L
Forzan Monica M
Gambaro Giovanni G
Giegling Ina I
Gonidakis Fragiskos F
Gorwood Philip P
Mayora Monica Gratacos MG
Guo Yiran Y
Halmi Katherine A KA
Hatzikotoulas Konstantinos K
Hebebrand Johannes J
Helder Sietske G SG
Herpertz-Dahlmann Beate B
Herzog Wolfgang W
Hinney Anke A
Imgart Hartmut H
Jiménez-Murcia Susana S
Johnson Craig C
Jordan Jennifer J
Julià Antonio A
Kaminská Deborah D
Karhunen Leila L
Karwautz Andreas A
Kas Martien J H MJH
Kaye Walter H WH
Kennedy Martin A MA
Kim Youl-Ri YR
Klareskog Lars L
Klump Kelly L KL
Knudsen Gun Peggy S GPS
Landén Mikael M
Le Hellard Stephanie S
Levitan Robert D RD
Li Dong D
Lichtenstein Paul P
Maj Mario M
Marsal Sara S
McDevitt Sara S
Mitchell James J
Monteleone Palmiero P
Monteleone Alessio Maria AM
Munn-Chernoff Melissa A MA
Nacmias Benedetta B
Navratilova Marie M
O'Toole Julie K JK
Padyukov Leonid L
Pantel Jacques J
Papezova Hana H
Rabionet Raquel R
Raevuori Anu A
Ramoz Nicolas N
Reichborn-Kjennerud Ted T
Ricca Valdo V
Roberts Marion M
Rujescu Dan D
Rybakowski Filip F
Scherag André A
Schmidt Ulrike U
Seitz Jochen J
Slachtova Lenka L
Slof-Op't Landt Margarita C T MCT
Slopien Agnieszka A
Sorbi Sandro S
Southam Lorraine L
Strober Michael M
Tortorella Alfonso A
Tozzi Federica F
Treasure Janet J
Tziouvas Konstantinos K
van Elburg Annemarie A AA
Wade Tracey D TD
Wagner Gudrun G
Walton Esther E
Watson Hunna J HJ
Wichmann H-Erich HE
Woodside D Blake DB
Zeggini Eleftheria E
Zerwas Stephanie S
Zipfel Stephan S
Adams Mark J MJ
Andlauer Till F M TFM
Berger Klaus K
Binder Elisabeth B EB
Boomsma Dorret I DI
Castelao Enrique E
Colodro-Conde Lucía L
Direk Nese N
Docherty Anna R AR
Domenici Enrico E
Domschke Katharina K
Dunn Erin C EC
Foo Jerome C JC
de Geus E J C EJC
Grabe Hans J HJ
Hamilton Steven P SP
Horn Carsten C
Hottenga Jouke-Jan JJ
Howard David D
Ising Marcus M
Kloiber Stefan S
Levinson Douglas F DF
Lewis Glyn G
Magnusson Patrik K E PKE
Mbarek Hamdi H
Middeldorp Christel M CM
Mostafavi Sara S
Nyholt Dale R DR
Penninx Brenda Wjh BW
Peterson Roseann E RE
Pistis Giorgio G
Porteous David J DJ
Preisig Martin M
Quiroz Jorge A JA
Schaefer Catherine C
Schulte Eva C EC
Shi Jianxin J
Smith Daniel J DJ
Thomson Pippa A PA
Tiemeier Henning H
Uher Rudolf R
van der Auwera Sandra S
Weissman Myrna M MM
Alexander Madeline M
Begemann Martin M
Bramon Elvira E
Buccola Nancy G NG
Cairns Murray J MJ
Campion Dominique D
Carr Vaughan J VJ
Cloninger C Robert CR
Cohen David D
Collier David A DA
Corvin Aiden A
DeLisi Lynn E LE
Donohoe Gary G
Dudbridge Frank F
Duan Jubao J
Freedman Robert R
Gejman Pablo V PV
Golimbet Vera V
Godard Stephanie S
Ehrenreich Hannelore H
Hartmann Annette M AM
Henskens Frans A FA
Ikeda Masashi M
Iwata Nakao N
Jablensky Assen V AV
Joa Inge I
Jönsson Erik G EG
Kelly Brian J BJ
Knight Jo J
Konte Bettina B
Laurent-Levinson Claudine C
Lee Jimmy J
Lencz Todd T
Lerer Bernard B
Loughland Carmel M CM
Malhotra Anil K AK
Mallet Jacques J
McDonald Colm C
Mitjans Marina M
Mowry Bryan J BJ
Murphy Kieran C KC
Murray Robin M RM
O'Neill F Anthony FA
Oh Sang-Yun SY
Palotie Aarno A
Pantelis Christos C
Pulver Ann E AE
Petryshen Tracey L TL
Quested Digby J DJ
Riley Brien B
Sanders Alan R AR
Schall Ulrich U
Schwab Sibylle G SG
Scott Rodney J RJ
Sham Pak C PC
Silverman Jeremy M JM
Sim Kang K
Steixner Agnes A AA
Tooney Paul A PA
van Os Jim J
Vawter Marquis P MP
Walsh Dermot D
Weiser Mark M
Wildenauer Dieter B DB
Williams Nigel M NM
Wormley Brandon K BK
Zhang Fuquan F
Androutsos Christos C
Arnold Paul D PD
Barr Cathy L CL
Barta Csaba C
Bey Katharina K
Bienvenu O Joseph OJ
Black Donald W DW
Brown Lawrence W LW
Budman Cathy C
Cath Danielle D
Cheon Keun-Ah KA
Ciullo Valentina V
Coffey Barbara J BJ
Cusi Daniele D
Davis Lea K LK
Denys Damiaan D
Depienne Christel C
Dietrich Andrea A
Eapen Valsamma V
Falkai Peter P
Fernandez Thomas V TV
Garcia-Delgar Blanca B
Geller Daniel A DA
Gilbert Donald L DL
Grados Marco A MA
Greenberg Erica E
Grünblatt Edna E
Hagstrøm Julie J
Hanna Gregory L GL
Hartmann Andreas A
Hedderly Tammy T
Heiman Gary A GA
Heyman Isobel I
Hong Hyun Ju HJ
Huang Alden A
Huyser Chaim C
Ibanez-Gomez Laura L
Khramtsova Ekaterina A EA
Kim Young Key YK
Kim Young-Shin YS
King Robert A RA
Koh Yun-Joo YJ
Konstantinidis Anastasios A
Kook Sodahm S
Kuperman Samuel S
Leventhal Bennett L BL
Lochner Christine C
Ludolph Andrea G AG
Madruga-Garrido Marcos M
Malaty Irene I
Maras Athanasios A
McCracken James T JT
Meijer Inge A IA
Mir Pablo P
Morer Astrid A
Müller-Vahl Kirsten R KR
Münchau Alexander A
Murphy Tara L TL
Naarden Allan A
Nagy Peter P
Nestadt Gerald G
Nestadt Paul S PS
Nicolini Humberto H
Nurmi Erika L EL
Okun Michael S MS
Paschou Peristera P
Piras Fabrizio F
Piras Federica F
Pittenger Christopher C
Plessen Kerstin J KJ
Richter Margaret A MA
Rizzo Renata R
Robertson Mary M
Roessner Veit V
Ruhrmann Stephan S
Samuels Jack F JF
Sandor Paul P
Schlögelhofer Monika M
Shin Eun-Young EY
Singer Harvey H
Song Dong-Ho DH
Song Jungeun J
Spalletta Gianfranco G
Stein Dan J DJ
Stewart S Evelyn SE
Storch Eric A EA
Stranger Barbara B
Stuhrmann Manfred M
Tarnok Zsanett Z
Tischfield Jay A JA
Tübing Jennifer J
Visscher Frank F
Vulink Nienke N
Wagner Michael M
Walitza Susanne S
Wanderer Sina S
Woods Martin M
Worbe Yulia Y
Zai Gwyneth G
Zinner Samuel H SH
Sullivan Patrick F PF
Franke Barbara B
Daly Mark J MJ
Bulik Cynthia M CM
Lewis Cathryn M CM
McIntosh Andrew M AM
O'Donovan Michael C MC
Zheutlin Amanda A
Andreassen Ole A OA
Børglum Anders D AD
Breen Gerome G
Edenberg Howard J HJ
Fanous Ayman H AH
Faraone Stephen V SV
Gelernter Joel J
Mathews Carol A CA
Mattheisen Manuel M
Mitchell Karen S KS
Neale Michael C MC
Nurnberger John I JI
Ripke Stephan S
Santangelo Susan L SL
Scharf Jeremiah M JM
Stein Murray B MB
Thornton Laura M LM
Walters James T R JTR
Wray Naomi R NR
Geschwind Daniel H DH
Neale Benjamin M BM
Kendler Kenneth S KS
Smoller Jordan W JW
JOURNAL
VOLUME: 179
ISSUE: 7
TITLE: Cell
ISOABBREVIATION: Cell
YEAR: 2019
MONTH: Dec
DAY: 12
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1097-4172
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Cell
COUNTRY: United States
ISSNLINKING: 0092-8674
NLMUNIQUEID: 0413066
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
GWAS
Psychiatric genetics
cross-disorder genetics
functional genomics
gene expression
genetic architecture
genetic correlation
neurodevelopment
pleiotropy
psychiatric disorders
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's