A Genome-wide Association Analysis of a Broad Psychosis Phenotype Identifies Three Loci for Further Investigation

Elvira Bramon; Matti Pirinen; Amy Strange; Kuang Lin; Colin Freeman; Celine Bellenguez; Zhan Su; Gavin Band; Richard Pearson; Damjan Vukcevic; Cordelia Langford; Panos Deloukas; Sarah Hunt; Emma Gray; Serge Dronov; Simon C. Potter; Avazeh Tashakkori-Ghanbaria; Sarah Edkins; Suzannah J. Bumpstead; Maria J. Arranz; Steven Bakker; Stephan Bender; Richard Bruggeman; Wiepke Cahn; David Chandler; David A. Collier; Benedicto Crespo-Facorro; Paola Dazzan; Lieuwe de Haan; Marta di Forti; Milan Dragovic; Ina Giegling; Jeremy Hall; Conrad Iyegbe; Assen Jablensky; Rene S. Kahn; Luba Kalaydjieva; Eugenia Kravariti; Stephen Lawrie; Don H. Lins-Zen; Ignacio Mata; Colm McDonald; Andrew McIntosh; Inez Myin-Germeys; Roel A. Ophoff; Carmine M. Pariante; Tiina Paunio; Marco Picchioni; Stephan Ripke; Dan Rujescu; Heinrich Sauer; Madiha Shaikh; Jessika Sussmann; Jaana Suvisaari; Sarah Tosato; Timothea Toulopoulou; Jim Van Os; Muriel Walshe; Matthias Weisbrod; Heather Whalley; Durk Wiersma; Jenefer M. Blackwell; Matthew A. Brown; Juan P. Casas; Aiden Corvin; Audrey Duncanson; Janusz A. Z. Jankowski; Hugh S. Markus; Christopher G. Mathew; Colin N. A. Palmer; Robert Plomin; Anna Rautanen; Stephen J. Sawcer; Richard C. Trembath; Nicholas W. Wood; Ines Barroso; Leena Peltonen; Cathryn M. Lewis; Robin M. Murray; Peter Donnelly; John Powell; Chris C. A. Spencer; Psychiat Genomics Consortium

doi:10.1016/j.biopsych.2013.03.033

Back

A Genome-wide Association Analysis of a Broad Psychosis Phenotype Identifies Three Loci for Further Investigation

Journal article

Peer reviewed

A Genome-wide Association Analysis of a Broad Psychosis Phenotype Identifies Three Loci for Further Investigation

Elvira Bramon, Matti Pirinen, Amy Strange, Kuang Lin, Colin Freeman, Celine Bellenguez, Zhan Su, Gavin Band, Richard Pearson, Damjan Vukcevic, …

Biological psychiatry (1969), Vol.75(5), pp.386-397

01/03/2014

DOI: https://doi.org/10.1016/j.biopsych.2013.03.033

PMCID: PMC3923972

PMID: 23871474

Abstract

Life Sciences & Biomedicine

Neurosciences

Neurosciences & Neurology

Psychiatry

Science & Technology

Background: Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. Methods: 1239 cases with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder; 857 of their unaffected relatives, and 2739 healthy controls were genotyped with the Affymetrix 6.0 single nucleotide polymorphism (SNP) array. Analyses of 695,193 SNPs were conducted using UNPHASED, which combines information across families and unrelated individuals. We attempted to replicate signals found in 23 genomic regions using existing data on nonoverlapping samples from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus cohorts (10,352 schizophrenia patients and 24,474 controls). Results: No individual SNP showed compelling evidence for association with psychosis in our data. However, we observed a trend for association with same risk alleles at loci previously associated with schizophrenia (one-sided p.003). A polygenic score analysis found that the Psychiatric GWAS Consortium's panel of SNPs associated with schizophrenia significantly predicted disease status in our sample (p = 5 x 10(-14)) and explained approximately 2% of the phenotypic variance. Conclusions: Although narrowly defined phenotypes have their advantages, we believe new loci may also be discovered through metaanalysis across broad phenotypes. The novel statistical methodology we introduced to model effect size heterogeneity between studies should help future GWAS that combine association evidence from related phenotypes. Applying these approaches, we highlight three loci that warrant further investigation. We found that SNPs conveying risk for schizophrenia are also predictive of disease status in our data.

Metrics

1 Record Views

See more details

Details

Title: A Genome-wide Association Analysis of a Broad Psychosis Phenotype Identifies Three Loci for Further Investigation
Creators - without role: Elvira Bramon - UCL, Mental Hlth Sci Unit, London WC1E 6BT, England
Matti Pirinen - University of Oxford
Amy Strange - University of Oxford
Kuang Lin - Kings Coll London, Inst Psychiat, London, England
Colin Freeman - University of Oxford
Celine Bellenguez - University of Oxford
Zhan Su - University of Oxford
Gavin Band - University of Oxford
Richard Pearson - University of Oxford
Damjan Vukcevic - University of Oxford
Cordelia Langford - Wellcome Sanger Institute
Panos Deloukas - Wellcome Sanger Institute
Sarah Hunt - Wellcome Sanger Institute
Emma Gray - Wellcome Sanger Institute
Serge Dronov - Wellcome Sanger Institute
Simon C. Potter - Wellcome Sanger Institute
Avazeh Tashakkori-Ghanbaria - Wellcome Sanger Institute
Sarah Edkins - Wellcome Sanger Institute
Suzannah J. Bumpstead - Kings Coll London, Inst Psychiat, London, England
Maria J. Arranz - Universitat de Barcelona
Steven Bakker - College Station Medical Center
Stephan Bender - Tech Univ Dresden, Dresden, Germany
Richard Bruggeman - University of Groningen
Wiepke Cahn - College Station Medical Center
David Chandler - University of Western Australia
David A. Collier - Kings Coll London, Inst Psychiat, London, England
Benedicto Crespo-Facorro - Universidad de Cantabria
Paola Dazzan - Kings Coll London, Inst Psychiat, London, England
Lieuwe de Haan - University of Amsterdam
Marta di Forti - Kings Coll London, Inst Psychiat, London, England
Milan Dragovic - University of Western Australia
Ina Giegling - Univ Munich, Dept Psychiat, D-80539 Munich, Germany
Jeremy Hall - University of Edinburgh
Conrad Iyegbe - Kings Coll London, Inst Psychiat, London, England
Assen Jablensky - University of Western Australia
Rene S. Kahn - College Station Medical Center
Luba Kalaydjieva - University of Western Australia
Eugenia Kravariti - Kings Coll London, Inst Psychiat, London, England
Stephen Lawrie - University of Edinburgh
Don H. Lins-Zen - University of Amsterdam
Ignacio Mata - Universidad de Cantabria
Colm McDonald - Natl Univ Ireland, Inst Clin Sci, Dept Psychiat, Galway, Ireland
Andrew McIntosh - University of Edinburgh
Inez Myin-Germeys - Univ Munich, Dept Psychiat, D-80539 Munich, Germany
Roel A. Ophoff - College Station Medical Center
Carmine M. Pariante - Kings Coll London, Inst Psychiat, London, England
Tiina Paunio - Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland
Marco Picchioni - Kings Coll London, Inst Psychiat, London, England
Stephan Ripke - Harvard University
Dan Rujescu - Univ Munich, Dept Psychiat, D-80539 Munich, Germany
Heinrich Sauer - Univ Hosp Jena, Dept Psychiat & Psychotherapy, Jena, Germany
Madiha Shaikh - Kings Coll London, Inst Psychiat, London, England
Jessika Sussmann - University of Edinburgh
Jaana Suvisaari - Natl Inst Hlth & Welf, Dept Mental Hlth & Substance Abuse Serv, Helsinki, Finland
Sarah Tosato - University of Verona
Timothea Toulopoulou - Kings Coll London, Inst Psychiat, London, England
Jim Van Os - Kings Coll London, Inst Psychiat, London, England
Muriel Walshe - Kings Coll London, Inst Psychiat, London, England
Matthias Weisbrod - Heidelberg
Heather Whalley - University of Edinburgh
Durk Wiersma - University of Groningen
Jenefer M. Blackwell - University of Western Australia
Matthew A. Brown - University of Queensland
Juan P. Casas - Supreme Council Of Health
Aiden Corvin - College Station Medical Center
Audrey Duncanson
Janusz A. Z. Jankowski - Queen Mary University of London
Hugh S. Markus - University of London
Christopher G. Mathew - College Station Medical Center
Colin N. A. Palmer - Supreme Council Of Health
Robert Plomin - Kings Coll London, Ctr Inst Psychiat, London, England
Anna Rautanen - University of Oxford
Stephen J. Sawcer - University of Cambridge
Richard C. Trembath - University of London
Nicholas W. Wood
Ines Barroso - Wellcome Sanger Institute
Leena Peltonen - Wellcome Sanger Institute
Cathryn M. Lewis - Kings Coll London, Inst Psychiat, London, England
Robin M. Murray - Kings Coll London, Inst Psychiat, London, England
Peter Donnelly - University of Oxford
John Powell - Kings Coll London, Inst Psychiat, London, England
Chris C. A. Spencer - University of Oxford
Psychiat Genomics Consortium
Publication Details: Biological psychiatry (1969), Vol.75(5), pp.386-397
Publisher: Elsevier
Number of pages: 12
Grant note: Institute of Psychiatry Kings College London; General Electric Wellcome Trust HEALTH-F2-2009-241909 / EU Seventh Framework Programme Wellcome Trust Research Training Fellowship; Wellcome Trust PDA/02/06/016 / National Institute for Health Research; National Institutes of Health Research (NIHR) MRC Centenary Award; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 068545/Z/02 / Wellcome Trust Schizophrenia Research Fund G0000934 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 10-000-1002 / Geestkracht programme of the Dutch Health Research Council WE-1996/ 1-3 / German Research Community (Deutsche Forschungsgemeinschaft, DFG); German Research Foundation (DFG) 085475/B/08/Z; 085475/Z/08/Z / Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project; Wellcome Trust People of the British Isles collection Brain and Behavior Research foundation's (NARSAD's) Young Investigator Award 513874 / National Health and Medical Research Council, Australia; National Health and Medical Research Council (NHMRC) of Australia Health Foundation Clinician Scientist Award PI020499; PI050427; PI060507 / Instituto de Salud Carlos III; Spanish Government Royal Society Wolfson Merit Award; Royal Society National Institute of Health Research UK; National Institutes of Health Research (NIHR) Psychiatry Research Trust API07/011; API10/13 / Fundacion Marques de Valdecilla; Instituto de Salud Carlos III UK National Blood Service controls CI 20050308007 / SENY Fundacic Fundacion Ramon Areces Royal Society Dorothy Hodgkin Fellowship; Royal Society NIHR Biomedical Research Centre for Mental Health at the South London; National Institutes of Health Research (NIHR) 257654 / Academy of Finland; Research Council of Finland 1R01MH078075 / NIMH grant 072894/Z/03/Z; 090532/Z/09/Z; 075491/Z/04/B / Wellcome Trust Centre for Human Genetics core grants North Metropolitan Health Service, Perth, Australia G1100583; G0901310; G0000934 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Maudsley NHS Foundation Trust NARSAD independent investigator award; NARSAD 097364/Z/11/Z / Wellcome Trust Fellowship; Wellcome Trust Wellcome Trust Clinical Research Training Fellowship; Wellcome Trust MRC New Investigator Award; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 064971 / Wellcome Trust Research Training Fellowship; Wellcome Trust G0901310; G0000934; G1100583; G9817803B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 9936200308331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article