CONTEXT: Cortical thickness is a highly heritable structural brain measurement, and reduced thickness has been associated with schizophrenia, bipolar disorder, and decreased cognitive performance among healthy control individuals. Identifying genes that contribute to variation in cortical thickness provides a means to elucidate some of the biological mechanisms underlying these diseases and general cognitive abilities. OBJECTIVES: To identify common genetic variants that affect cortical thickness in patients with schizophrenia, patients with bipolar disorder, and controls and to test these variants for association with cognitive performance. DESIGN: A total of 597 198 single-nucleotide polymorphisms were tested for association with average cortical thickness in a genome-wide association study. Significantly associated single-nucleotide polymorphisms were tested for their effect on several measures of cognitive performance. SETTING: Four major hospitals in Oslo, Norway. PARTICIPANTS: A total of 1054 case individuals and controls were analyzed in the genome-wide association study and follow-up cognitive study. The genome-wide association study included controls (n = 181) and individuals with DSM-IV -diagnosed schizophrenia spectrum disorder (n = 94), bipolar spectrum disorder (n = 97), and other psychotic and affective disorders (n = 49). MAIN OUTCOME MEASURES: Cortical thickness measured with magnetic resonance imaging and cognitive performance as assessed by several neuropsychological tests. RESULTS: Two closely linked genetic variants (rs4906844 and rs11633924) within the Prader-Willi and Angelman syndrome region on chromosome 15q12 showed a genome-wide significant association (P = 1.1 x 10(-8) with average cortical thickness and modest association with cognitive performance (permuted P = .03) specifically among patients diagnosed as having schizophrenia. CONCLUSION: This genome-wide association study identifies a common genetic variant that contributes to the heritable reduction of cortical thickness in schizophrenia. These results highlight the usefulness of cortical thickness as an intermediate phenotype for neuropsychiatric diseases. Future independent replication studies are required to confirm these findings.
CONTEXT: Cortical thickness is a highly heritable structural brain measurement, and reduced thickness has been associated with schizophrenia, bipolar disorder, and decreased cognitive performance among healthy control individuals. Identifying genes that contribute to variation in cortical thickness provides a means to elucidate some of the biological mechanisms underlying these diseases and general cognitive abilities. OBJECTIVES: To identify common genetic variants that affect cortical thickness in patients with schizophrenia, patients with bipolar disorder, and controls and to test these variants for association with cognitive performance. DESIGN: A total of 597 198 single-nucleotide polymorphisms were tested for association with average cortical thickness in a genome-wide association study. Significantly associated single-nucleotide polymorphisms were tested for their effect on several measures of cognitive performance. SETTING: Four major hospitals in Oslo, Norway. PARTICIPANTS: A total of 1054 case individuals and controls were analyzed in the genome-wide association study and follow-up cognitive study. The genome-wide association study included controls (n = 181) and individuals with DSM-IV -diagnosed schizophrenia spectrum disorder (n = 94), bipolar spectrum disorder (n = 97), and other psychotic and affective disorders (n = 49). MAIN OUTCOME MEASURES: Cortical thickness measured with magnetic resonance imaging and cognitive performance as assessed by several neuropsychological tests. RESULTS: Two closely linked genetic variants (rs4906844 and rs11633924) within the Prader-Willi and Angelman syndrome region on chromosome 15q12 showed a genome-wide significant association (P = 1.1 x 10(-8) with average cortical thickness and modest association with cognitive performance (permuted P = .03) specifically among patients diagnosed as having schizophrenia. CONCLUSION: This genome-wide association study identifies a common genetic variant that contributes to the heritable reduction of cortical thickness in schizophrenia. These results highlight the usefulness of cortical thickness as an intermediate phenotype for neuropsychiatric diseases. Future independent replication studies are required to confirm these findings.
Authors: Katherine L Narr; Roger P Woods; Paul M Thompson; Philip Szeszko; Delbert Robinson; Teodora Dimtcheva; Mala Gurbani; Arthur W Toga; Robert M Bilder Journal: Cereb Cortex Date: 2006-11-21 Impact factor: 5.357
Authors: Kristine B Walhovd; Anders M Fjell; Anders M Dale; Bruce Fischl; Brian T Quinn; Nikos Makris; David Salat; Ivar Reinvang Journal: Neuroimage Date: 2006-03-15 Impact factor: 6.556
Authors: Michael C O'Donovan; Nicholas Craddock; Nadine Norton; Hywel Williams; Timothy Peirce; Valentina Moskvina; Ivan Nikolov; Marian Hamshere; Liam Carroll; Lyudmila Georgieva; Sarah Dwyer; Peter Holmans; Jonathan L Marchini; Chris C A Spencer; Bryan Howie; Hin-Tak Leung; Annette M Hartmann; Hans-Jürgen Möller; Derek W Morris; Yongyong Shi; GuoYin Feng; Per Hoffmann; Peter Propping; Catalina Vasilescu; Wolfgang Maier; Marcella Rietschel; Stanley Zammit; Johannes Schumacher; Emma M Quinn; Thomas G Schulze; Nigel M Williams; Ina Giegling; Nakao Iwata; Masashi Ikeda; Ariel Darvasi; Sagiv Shifman; Lin He; Jubao Duan; Alan R Sanders; Douglas F Levinson; Pablo V Gejman; Sven Cichon; Markus M Nöthen; Michael Gill; Aiden Corvin; Dan Rujescu; George Kirov; Michael J Owen; Nancy G Buccola; Bryan J Mowry; Robert Freedman; Farooq Amin; Donald W Black; Jeremy M Silverman; William F Byerley; C Robert Cloninger Journal: Nat Genet Date: 2008-09 Impact factor: 38.330
Authors: Andrew D Johnson; Robert E Handsaker; Sara L Pulit; Marcia M Nizzari; Christopher J O'Donnell; Paul I W de Bakker Journal: Bioinformatics Date: 2008-10-30 Impact factor: 6.937
Authors: Jianxin Shi; Douglas F Levinson; Jubao Duan; Alan R Sanders; Yonglan Zheng; Itsik Pe'er; Frank Dudbridge; Peter A Holmans; Alice S Whittemore; Bryan J Mowry; Ann Olincy; Farooq Amin; C Robert Cloninger; Jeremy M Silverman; Nancy G Buccola; William F Byerley; Donald W Black; Raymond R Crowe; Jorge R Oksenberg; Daniel B Mirel; Kenneth S Kendler; Robert Freedman; Pablo V Gejman Journal: Nature Date: 2009-07-01 Impact factor: 49.962
Authors: Aaron L Goldman; Lukas Pezawas; Venkata S Mattay; Bruce Fischl; Beth A Verchinski; Qiang Chen; Daniel R Weinberger; Andreas Meyer-Lindenberg Journal: Arch Gen Psychiatry Date: 2009-05
Authors: Andrés Ingason; George Kirov; Ina Giegling; Thomas Hansen; Anthony R Isles; Klaus D Jakobsen; Kari T Kristinsson; Louise le Roux; Omar Gustafsson; Nick Craddock; Hans-Jürgen Möller; Andrew McQuillin; Pierandrea Muglia; Sven Cichon; Marcella Rietschel; Roel A Ophoff; Srdjan Djurovic; Ole A Andreassen; Olli P H Pietiläinen; Leena Peltonen; Emma Dempster; David A Collier; David St Clair; Henrik B Rasmussen; Birte Y Glenthøj; Lambertus A Kiemeney; Barbara Franke; Sarah Tosato; Chiara Bonetto; Evald Saemundsen; Stefán J Hreidarsson; Markus M Nöthen; Hugh Gurling; Michael C O'Donovan; Michael J Owen; Engilbert Sigurdsson; Hannes Petursson; Hreinn Stefansson; Dan Rujescu; Kari Stefansson; Thomas Werge Journal: Am J Psychiatry Date: 2011-02-15 Impact factor: 18.112
Authors: Hreinn Stefansson; Dan Rujescu; Sven Cichon; Olli P H Pietiläinen; Andres Ingason; Stacy Steinberg; Ragnheidur Fossdal; Engilbert Sigurdsson; Thordur Sigmundsson; Jacobine E Buizer-Voskamp; Thomas Hansen; Klaus D Jakobsen; Pierandrea Muglia; Clyde Francks; Paul M Matthews; Arnaldur Gylfason; Bjarni V Halldorsson; Daniel Gudbjartsson; Thorgeir E Thorgeirsson; Asgeir Sigurdsson; Adalbjorg Jonasdottir; Aslaug Jonasdottir; Asgeir Bjornsson; Sigurborg Mattiasdottir; Thorarinn Blondal; Magnus Haraldsson; Brynja B Magnusdottir; Ina Giegling; Hans-Jürgen Möller; Annette Hartmann; Kevin V Shianna; Dongliang Ge; Anna C Need; Caroline Crombie; Gillian Fraser; Nicholas Walker; Jouko Lonnqvist; Jaana Suvisaari; Annamarie Tuulio-Henriksson; Tiina Paunio; Timi Toulopoulou; Elvira Bramon; Marta Di Forti; Robin Murray; Mirella Ruggeri; Evangelos Vassos; Sarah Tosato; Muriel Walshe; Tao Li; Catalina Vasilescu; Thomas W Mühleisen; August G Wang; Henrik Ullum; Srdjan Djurovic; Ingrid Melle; Jes Olesen; Lambertus A Kiemeney; Barbara Franke; Chiara Sabatti; Nelson B Freimer; Jeffrey R Gulcher; Unnur Thorsteinsdottir; Augustine Kong; Ole A Andreassen; Roel A Ophoff; Alexander Georgi; Marcella Rietschel; Thomas Werge; Hannes Petursson; David B Goldstein; Markus M Nöthen; Leena Peltonen; David A Collier; David St Clair; Kari Stefansson Journal: Nature Date: 2008-09-11 Impact factor: 49.962
Authors: Lachlan T Strike; Baptiste Couvy-Duchesne; Narelle K Hansell; Gabriel Cuellar-Partida; Sarah E Medland; Margaret J Wright Journal: Neuropsychol Rev Date: 2015-03-14 Impact factor: 7.444
Authors: Mario Quarantelli; Olga Palladino; Anna Prinster; Vittorio Schiavone; Barbara Carotenuto; Arturo Brunetti; Angela Marsili; Margherita Casiello; Giovanni Muscettola; Marco Salvatore; Andrea de Bartolomeis Journal: Biomed Res Int Date: 2014-07-23 Impact factor: 3.411
Authors: Esther Walton; Daniel Geisler; Phil H Lee; Johanna Hass; Jessica A Turner; Jingyu Liu; Scott R Sponheim; Tonya White; Thomas H Wassink; Veit Roessner; Randy L Gollub; Vince D Calhoun; Stefan Ehrlich Journal: Schizophr Bull Date: 2013-12-10 Impact factor: 9.306