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Association at SYNE1 in both bipolar disorder and recurrent major depression

Molecular Psychiatry volume 18, pages 614–617 (2013)Cite this article

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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.

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Acknowledgements

We are indebted to all individuals who have participated in, or helped with, our research. We particularly thank those involved with MDF—the Bipolar Organization and the Bipolar Disorder Research Network (BDRN). Funding for the sample collection was provided by grants from the Wellcome Trust, Medical Research Council and the Stanley Medical Research Institute. Funding for the genotyping was provided by grants from the Wellcome Trust. We would like to thank the British 1958 Birth Cohort DNA (1958BC) and UK Blood Services collection of Common Controls (UKBC-CC collection) and funders for the control samples used in this study.

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Authors and Affiliations

  1. MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine,,

    E K Green, D Grozeva, L Forty, K Gordon-Smith, E Russell, M Hamshere, I R Jones, L Jones, M J Owen, M C O'Donovan & N Craddock

  2. Cardiff University, Heath Park, Cardiff, UK

    E K Green, D Grozeva, L Forty, K Gordon-Smith, E Russell, M Hamshere, I R Jones, L Jones, M J Owen, M C O'Donovan & N Craddock

  3. Department of Psychiatry, National Centre for Mental Health, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK

    K Gordon-Smith

  4. MRC SGDP Centre, Institute of Psychiatry, King's College London, London, UK

    A Farmer & P McGuffin

  5. Stanley Centre for Psychiatric Research at the Broad Institute of MIT and Harvard, Cambridge, MA, USA

    J L Moran, S Purcell & P Sklar

  6. Mount Sinai School of Medicine, New York, NY, USA

    S Purcell & P Sklar

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  1. E K Green
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  2. D Grozeva
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  3. L Forty
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  6. A Farmer
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  8. I R Jones
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  9. L Jones
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Correspondence to E K Green.

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Green, E., Grozeva, D., Forty, L. et al. Association at SYNE1 in both bipolar disorder and recurrent major depression. Mol Psychiatry 18, 614–617 (2013). https://doi.org/10.1038/mp.2012.48

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