Association at SYNE1 in both bipolar disorder and recurrent major depression

• Published in: Molecular psychiatry Vol. 18; no. 5; pp. 614 - 617
• Main Authors: GREEN, E. K, GROZEVA, D, MORAN, J. L, PURCELL, S, SKLAR, P, OWEN, M. J, O'DONOVAN, M. C, CRADDOCK, N, FORTY, L, GORDON-SMITH, K, RUSSELL, E, FARMER, A, HAMSHERE, M, JONES, I. R, JONES, L, MCGUFFIN, P
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.2013
• Subjects: Adult; Adult and adolescent clinical studies; Analysis; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - genetics; Bipolar disorders; Depression; Depressive Disorder, Major - genetics; Diseases; Female; Gene Frequency; Gene polymorphism; Genetic aspects; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Genotype; Humans; Major depressive disorder; Male; Medical sciences; Mental depression; Middle Aged; Mood disorders; Nerve Tissue Proteins - genetics; Nuclear Proteins - genetics; Odds Ratio; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Recurrence; Relapse; Replication; Single nucleotide polymorphisms; Systematic review; United Kingdom; Mood disorder; Relapse; Depression; Genetics; Bipolar disorder; rs9371601; unipolar depression; SYNE1
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2012.48

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.