Biological insights from 108 schizophrenia-associated genetic loci

2014

Ripke, Stephan

Neale, Benjamin M

Pers, Tune H

Julia, Antonio

Kahn, Rene S

Kalaydjieva, Luba

Karachanak-Yankova, Sena

Karjalainen, Juha

Kavanagh, David

Keller, Matthew C

Kennedy, James L

Khrunin, Andrey

Kim, Yunjung

Agartz, Ingrid

Klovins, Janis

Knowles, James A

Konte, Bettina

Kucinskas, Vaidutis

Ausrele Kucinskiene, Zita

Kuzelova-Ptackova, Hana

Kahler, Anna K

Laurent, Claudine

Lee Chee Keong, Jimmy

Lee, Sang Hong

Agerbo, Esben

Legge, Sophie E

Lerer, Bernard

Li, Miaoxin

Li, Tao

Liang, Kung-Yee

Lieberman, Jeffrey

Limborska, Svetlana

Loughland, Carmel M

Lubinski, Jan

Lonnqvist, Jouko

Albus, Margot

Macek Jr, Milan

Magnusson, Patrik K E

Maher, Brion S

Maier, Wolfgang

Mallet, Jacques

Marsal, Sara

Mattheisen, Manuel

Mattingsdal, Morten

McCarley, Robert W

McDonald, Colm

Alexander, Madeline

McIntosh, Andrew M

Meier, Sandra

Meijer, Carin J

Melegh, Bela

Melle, Ingrid

Mesholam-Gately, Raquelle I

Metspalu, Andres

Michie, Patricia T

Milani, Lili

Milanova, Vihra

Amin, Farooq

Mokrab, Younes

Morris, Derek W

Mors, Ole

Murphy, Kieran C

Murray, Robin M

Myin-Germeys, Inez

Muller-Myhsok, Bertram

Nelis, Mari

Nenadic, Igor

Nertney, Deborah A

Bacanu, Silviu A

Nestadt, Gerald

Nicodemus, Kristin K

Nikitina-Zake, Liene

Nisenbaum, Laura

Nordin, Annelie

O'Callaghan, Eadbhard

O'Dushlaine, Colm

O'Neill, F Anthony

Oh, Sang-Yun

Olincy, Ann

Begemann, Martin

Olsen, Line

Van Os, Jim

Psychosis Endophenotypes International Consortium,

Pantelis, Christos

Papadimitriou, George N

Papiol, Sergi

Parkhomenko, Elena

Pato, Michele T

Paunio, Tiina

Pejovic-Milovancevic, Milica

Belliveau Jr, Richard A

Perkins, Diana O

Pietilainen, Olli

Pimm, Jonathan

Pocklington, Andrew J

Powell, John

Price, Alkes

Pulver, Ann E

Purcell, Shaun M

Quested, Digby

Rasmussen, Henrik B

Bene, Judit

Reichenberg, Abraham

Reimers, Mark A

Richards, Alexander L

Roffman, Joshua L

Roussos, Panos

Ruderfer, Douglas M

Salomaa, Veikko

Sanders, Alan R

Schall, Ulrich

Schubert, Christian R

Corvin, Aiden

Bergen, Sarah E

Schulze, Thomas G

Schwab, Sibylle G

Scolnick, Edward M

Scott, Rodney J

Seidman, Larry J

Shi, Jianxin

Sigurdsson, Engilbert

Silagadze, Teimuraz

Silverman, Jeremy M

Sim, Kang

Bevilacqua, Elizabeth

Slominsky, Petr

Smoller, Jordan W

So, Hon-Cheong

Spencer, Chris C A

Stahl, Eli A

Stefansson, Hreinn

Steinberg, Stacy

Stogmann, Elisabeth

Straub, Richard E

Strengman, Eric

Bigdeli, Tim B

Strohmaier, Jana

Stroup, T Scott

Subramaniam, Mythily

Suvisaari, Jaana

Svrakic, Dragan M

Szatkiewicz, Jin P

Soderman, Erik

Thirumalai, Srinivas

Toncheva, Draga

Tosato, Sarah

Black, Donald W

Veijola, Juha

Waddington, John

Walsh, Dermot

Wang, Dai

Wang, Qiang

Webb, Bradley T

Weiser, Mark

Wildenauer, Dieter B

Williams, Nigel M

Williams, Stephanie

Bruggeman, Richard

Witt, Stephanie H

Wolen, Aaron R

Wong, Emily H M

Wormley, Brandon K

Xi, Hualin Simon

Zai, Clement C

Zheng, Xuebin

Zimprich, Fritz

Wray, Naomi R

Stefansson, Kari

Buccola, Nancy G

Visscher, Peter M

Wellcome Trust Case-Control Consortium,

Adolfsson, Rolf

Andreassen, Ole A

Blackwood, Douglas H R

Bramon, Elvira

Buxbaum, Joseph D

Borglum, Anders D

Cichon, Sven

Darvasi, Ariel

Buckner, Randy L

Domenici, Enrico

Ehrenreich, Hannelore

Esko, Tonu

Gejman, Pablo V

Gill, Michael

Gurling, Hugh

Hultman, Christina M

Iwata, Nakao

Jablensky, Assen V

Jonsson, Erik G

Byerley, William

Kendler, Kenneth S

Kirov, George

Knight, Jo

Lencz, Todd

Levinson, Douglas F

Li, Qingqin S

Liu, Jianjun

Malhotra, Anil K

McCarroll, Steven A

McQuillin, Andrew

Cahn, Wiepke

Moran, Jennifer L

Mortensen, Preben B

Mowry, Bryan J

Nothen, Markus M

Ophoff, Roel A

Owen, Michael J

Palotie, Aarno

Pato, Carlos N

Petryshen, Tracey L

Posthuma, Danielle

Cai, Guiqing

Rietschel, Marcella

Riley, Brien P

Rujescu, Dan

Sham, Pak C

Sklar, Pamela

St Clair, David

Weinberger, Daniel R

Wendland, Jens R

Werge, Thomas

Daly, Mark J

Walters, James T R

Campion, Dominique

Sullivan, Patrick F

O'Donovan, Michael C

Cantor, Rita M

Carr, Vaughan J

Carrera, Noa

Catts, Stanley V

Chambert, Kimberly D

Chan, Raymond C K

Chen, Ronald Y L

Chen, Eric Y H

Cheng, Wei

Farh, Kai-How

Cheung, Eric F C

Chong, Siow Ann

Cloninger, C Robert

Cohen, David

Cohen, Nadine

Cormican, Paul

Craddock, Nick

Crowley, James J

Curtis, David

Davidson, Michael

Holmans, Peter A

Davis, Kenneth L

Degenhardt, Franziska

Del Favero, Jurgen

Demontis, Ditte

Dikeos, Dimitris

Dinan, Timothy

Djurovic, Srdjan

Donohoe, Gary

Drapeau, Elodie

Duan, Jubao

Lee, Phil

Dudbridge, Frank

Durmishi, Naser

Eichhammer, Peter

Eriksson, Johan

Escott-Price, Valentina

Essioux, Laurent

Fanous, Ayman H

Farrell, Martilias S

Frank, Josef

Franke, Lude

Bulik-Sullivan, Brendan

Freedman, Robert

Freimer, Nelson B

Friedl, Marion

Friedman, Joseph I

Fromer, Menachem

Genovese, Giulio

Georgieva, Lyudmila

Giegling, Ina

Giusti-Rodriguez, Paola

Godard, Stephanie

Collier, David A

Goldstein, Jacqueline I

Golimbet, Vera

Gopal, Srihari

Gratten, Jacob

de Haan, Lieuwe

Hammer, Christian

Hamshere, Marian L

Hansen, Mark

Hansen, Thomas

Haroutunian, Vahram

Huang, Hailiang

Hartmann, Annette M

Henskens, Frans A

Herms, Stefan

Hirschhorn, Joel N

Hoffmann, Per

Hofman, Andrea

Hollegaard, Mads V

Hougaard, David M

Ikeda, Masashi

Joa, Inge

Journal Article

en

Publication

Nature Publishing Group

United Kingdom

10.1038/nature13595

une:19095

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

link

Nature, 511(7510), p. 421-427

1476-4687

0028-0836

421

427