Support of association between BRD1 and both schizophrenia and bipolar affective disorder.
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.
Nyegaard
Mette
M
Institute of Human Genetics, University of Aarhus, Aarhus, Denmark.|Department of Haematology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
Severinsen
Jacob E
JE
Institute of Human Genetics, University of Aarhus, Aarhus, Denmark.
Als
Thomas D
TD
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
Hedemand
Anne
A
Institute of Human Genetics, University of Aarhus, Aarhus, Denmark.
Straarup
Steen
S
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
Nordentoft
Merete
M
Department of Psychiatry, Bispebjerg Hospital, Copenhagen, Denmark.
McQuillin
Andrew
A
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.
Bass
Nicholas
N
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.
Lawrence
Jacob
J
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.
Thirumalai
Srinivasa
S
West Berkshire NHS Trust, Reading, UK.
Pereira
Ana C P
ACP
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.
Kandaswamy
Radhika
R
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.
Lydall
Gregory J
GJ
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.
Sklar
Pamela
P
Broad Institute (MIT/Harvard), Boston, Massachusetts.
Scolnick
Edward
E
Broad Institute (MIT/Harvard), Boston, Massachusetts.
Purcell
Shaun
S
Broad Institute (MIT/Harvard), Boston, Massachusetts.
Curtis
David
D
Barts and the Royal London School of Medicine, Queen Mary College, London, UK.
Gurling
Hugh M D
HMD
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.
Mortensen
Preben B
PB
National Centre for Register-Based Research, University of Aarhus, Aarhus, Denmark.
Mors
Ole
O
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
Børglum
Anders D
AD
Institute of Human Genetics, University of Aarhus, Aarhus, Denmark.|Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
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
D005819:Genetic Markers; D051548:Histone Acetyltransferases; D056488:Histone Chaperones; D009687:Nuclear Proteins; C402649:BRD1 protein, human; D000092468:Bromodomain Containing Proteins