title: Common variant at 16p11.2 conferring risk of psychosis.
abstract: Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).
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authors.affiliation: 1] Center for Neurobehavioral Genetics, UCLA, Los Angeles, CA, USA [2] Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center, Utrecht, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Ophoff
authors.affiliation: 1] German Center for Neurodegenerative Disorders (DZNE), Bonn Germany [2] Institute of Human Genetics, University of Bonn, Bonn Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: 1] Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany [2] Institute of Human Genetics, University of Bonn, Bonn Germany [3] Institute of Neurosciences and Medicine (INM-1), Juelich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Cichon
authors.affiliation: Section of Psychiatry, University of Verona, Verona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ruggeri
authors.affiliation: Section of Psychiatry, University of Verona, Verona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Tosato
authors.affiliation: 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland [2] Wellcome Trust Sanger Institute, Cambridge, UK [3] Program in Medical and Population Genetics and Genetic Analysis Platform, The Broad Institute of MIT and Harvard, Cambridge, MA, USA [4] Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Palotie
authors.affiliation: Department of Mental Health, University of Aberdeen, Royal Cornhill Hospital, Aberdeen, UK.
authors.forename: D
authors.initials: D
authors.lastname: St Clair
authors.affiliation: 1] Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany [2] Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Rujescu
authors.affiliation: 1] Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London, UK [2] Eli Lilly and Co. Ltd, Erl Wood Manor, Windlesham, Surrey, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Collier
authors.affiliation: deCODE genetics, Reykjavik, Iceland.
authors.forename: H
authors.initials: H
authors.lastname: Stefansson
authors.affiliation: 1] deCODE genetics, Reykjavik, Iceland [2] School of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: K
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D002869:Chromosome Aberrations; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005060:Europe; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult