Association at SYNE1 in both bipolar disorder and recurrent major depression

Mol Psychiatry. 2013 May;18(5):614-7. doi: 10.1038/mp.2012.48. Epub 2012 May 8.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bipolar Disorder / genetics*
  • Cytoskeletal Proteins
  • Depressive Disorder, Major / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics*
  • Recurrence

Substances

  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • SYNE1 protein, human