Sex-specific association of the reelin gene with bipolar disorder

F. S. Goes, V. L. Willour, P. P. Zandi, P. L. Belmonte, D. F. MacKinnon, F. M. Mondimore, B. Schweizer, J. R. DePaulo, E. S. Gershon, F. J. McMahon, J. B. Potash

Research output: Contribution to journalArticlepeer-review

Abstract

The Reelin gene (RELN) encodes a secretory glycoprotein critical for brain development and synaptic plasticity. Post-mortem studies have shown lower Reelin protein levels in the brains of patientswith schizophrenia and bipolar disorder (BP) compared with controls. In a recent genome-wide association study of schizophrenia, the strongest association was found in a marker within RELN, although this association was seen only in women. In this study, we investigated whether genetic variation in RELN is associated with BP in a large family sample. We genotyped 75 tagSNPs and 6 coding SNPs in 1,188 individuals from 318 nuclear families, including 554 affected offspring. Quality control measures, transmission-disequilibrium tests (TDTs), and empirical simulations were performed in PLINK. We found a significant overtransmission of the C allele of rs362719 to BP offspring (OR=1.47, P=5.9 x 10-4); this withstood empirical correction for testing of multiple markers (empirical P=0.048). In a hypothesis-driven secondary analysis, we found that the association with rs362719 was almost entirely accounted for by overtransmission of the putative risk allele to affected females (ORFemale = 1.79, P = 8.9 x 10 -5 vs. ORMale = 1.12, P = 0.63). These results provide preliminary evidence that genetic variation in RELN is associated with susceptibility to BP and, in particular, to BP in females. However, our findings should be interpreted with caution until further replication and functional assays provide convergent support.

Original languageEnglish (US)
Pages (from-to)549-553
Number of pages5
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153
Issue number2
DOIs
StatePublished - Mar 2010

Keywords

  • Bipolar disorder
  • Genetics
  • Neurodevelopment
  • Overlap
  • Schizophrenia

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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