title: Association at SYNE1 in both bipolar disorder and recurrent major depression.
abstract: Genome-wide association studies (GWAS) have identified a number of loci that have strong support for their association with bipolar disorder (BD). The Psychiatric Genome-Wide Association Study (GWAS) Consortium Bipolar Disorder Working Group (PGC-BD) meta-analysis of BD GWAS data sets and replication samples identified evidence (P=6.7 × 10⁻⁷, odds ratio (OR)=1.147) of association with the risk of BD at the polymorphism rs9371601 within SYNE1, a gene which encodes nesprin-1. Here we have tested this polymorphism in an independent BD case (n=1527) and control (n=1579) samples, and find evidence for association (P=0.0095) with similar effect sizes to those previously observed in BD (allelic OR=1.148). In a combined (meta) analysis of PGC-BD data (both primary and replication data) and our independent BD samples, we found genome-wide significant evidence for association (P=2.9 × 10⁻⁸, OR=1.104). We have also examined the polymorphism in our recurrent unipolar depression cases (n=1159) and control (n=2592) sample, and found that the risk allele was associated with risk for recurrent major depression (P=0.032, OR=1.118). Our findings add to the evidence that association at this locus influences susceptibility to bipolar and unipolar mood disorders.
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Heath Park, Cardiff, UK. greenek@cardiff.ac.uk
authors.forename: E K
authors.initials: EK
authors.lastname: Green
authors.forename: D
authors.initials: D
authors.lastname: Grozeva
authors.forename: L
authors.initials: L
authors.lastname: Forty
authors.forename: K
authors.initials: K
authors.lastname: Gordon-Smith
authors.forename: E
authors.initials: E
authors.lastname: Russell
authors.forename: A
authors.initials: A
authors.lastname: Farmer
authors.forename: M
authors.initials: M
authors.lastname: Hamshere
authors.forename: I R
authors.initials: IR
authors.lastname: Jones
authors.forename: L
authors.initials: L
authors.lastname: Jones
authors.forename: P
authors.initials: P
authors.lastname: McGuffin
authors.forename: J L
authors.initials: JL
authors.lastname: Moran
authors.forename: S
authors.initials: S
authors.lastname: Purcell
authors.forename: P
authors.initials: P
authors.lastname: Sklar
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: N
authors.initials: N
authors.lastname: Craddock
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D003598:Cytoskeletal Proteins; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012008:Recurrence
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C415465:SYNE1 protein, human