title: Support of association between BRD1 and both schizophrenia and bipolar affective disorder.
abstract: A recent study published by our group implicated the bromodomain containing protein 1 (BRD1) gene located at chromosome 22q13.33 with schizophrenia (SZ) and bipolar affective disorder (BPD) susceptibility and provided evidence suggesting a possible role for BRD1 in neurodevelopment. The present study reports an association analysis of BRD1 and the neighboring gene ZBED4 using a Caucasian case-control sample from Denmark and England (UK/DK sample: 490 patients with BPD, 527 patients with SZ, and 601 control individuals), and genotypes obtained from a BPD genome wide association (GWA) study of an overlapping English sample comprising 506 patients with BPD and 510 control individuals (UCL sample). In the UK/DK sample we genotyped 11 SNPs in the BRD1 region, of which six showed association with SZ (minimal single marker P-values of 0.0014), including two SNPs that previously showed association in a Scottish population [Severinsen et al. (2006); Mol Psychiatry 11(12): 1126-1138]. Haplotype analysis revealed specific risk as well as protective haplotypes with a minimal P-value of 0.0027. None of the 11 SNPs showed association with BPD. However, analyzing seven BRD1 SNPs obtained from the BPD GWA study, positive associations with BPD was observed with all markers (minimal P-value of 0.0014). The associations reported add further support for the implication of BRD1 with SZ and BPD susceptibility.
authors.affiliation: Institute of Human Genetics, University of Aarhus, Aarhus, Denmark.|Department of Haematology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Nyegaard
authors.affiliation: Institute of Human Genetics, University of Aarhus, Aarhus, Denmark.
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Severinsen
authors.affiliation: Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Als
authors.affiliation: Institute of Human Genetics, University of Aarhus, Aarhus, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Hedemand
authors.affiliation: Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Straarup
authors.affiliation: Department of Psychiatry, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Nordentoft
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute for Medical Science, Royal Free and University College Medical School, University College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute for Medical Science, Royal Free and University College Medical School, University College London, London, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bass
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute for Medical Science, Royal Free and University College Medical School, University College London, London, UK.
authors.forename: Jacob
authors.initials: J
authors.lastname: Lawrence
authors.affiliation: West Berkshire NHS Trust, Reading, UK.
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Thirumalai
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute for Medical Science, Royal Free and University College Medical School, University College London, London, UK.
authors.forename: Ana C P
authors.initials: ACP
authors.lastname: Pereira
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute for Medical Science, Royal Free and University College Medical School, University College London, London, UK.
authors.forename: Radhika
authors.initials: R
authors.lastname: Kandaswamy
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute for Medical Science, Royal Free and University College Medical School, University College London, London, UK.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Lydall
authors.affiliation: Broad Institute (MIT/Harvard), Boston, Massachusetts.
authors.forename: Pamela
authors.initials: P
authors.lastname: Sklar
authors.affiliation: Broad Institute (MIT/Harvard), Boston, Massachusetts.
authors.forename: Edward
authors.initials: E
authors.lastname: Scolnick
authors.affiliation: Broad Institute (MIT/Harvard), Boston, Massachusetts.
authors.forename: Shaun
authors.initials: S
authors.lastname: Purcell
authors.affiliation: Barts and the Royal London School of Medicine, Queen Mary College, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Curtis
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute for Medical Science, Royal Free and University College Medical School, University College London, London, UK.
authors.forename: Hugh M D
authors.initials: HMD
authors.lastname: Gurling
authors.affiliation: National Centre for Register-Based Research, University of Aarhus, Aarhus, Denmark.
authors.forename: Preben B
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.affiliation: Institute of Human Genetics, University of Aarhus, Aarhus, Denmark.|Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Børglum
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005192:Family Health; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D051548:Histone Acetyltransferases; D056488:Histone Chaperones; D006801:Humans; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D000092468:Bromodomain Containing Proteins
chemical_list: D005819:Genetic Markers; D051548:Histone Acetyltransferases; D056488:Histone Chaperones; D009687:Nuclear Proteins; C402649:BRD1 protein, human; D000092468:Bromodomain Containing Proteins