Sex‐specific association of the reelin gene with bipolar disorder
Open accessAbstract
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 patients with 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 × 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 (OR Female = 1.79, P = 8.9 × 10−5 vs. OR Male = 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. © 2009 Wiley‐Liss, Inc.
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Axonal guidance and reelin signaling are important pathways for nervous system development and have been implicated in neuropsychiatric disorders such as bipolar, SCZ, and ADHD.
“Axonal guidance and reelin signaling are important pathways for nervous system development and have been implicated in neuropsychiatric disorders such as bipolar, SCZ, and ADHD [64–68]”
From An integrated analysis of genes and functional pathways for aggression in human and rodent models (2019) · cites this paper as [68]
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- Authors
- Goes, F. S., Willour, V. L., Zandi, P. P., Belmonte, P. L., MacKinnon, D. F., Mondimore, F. M., Schweizer, B., National Institute of Mental Health Genetics Initiative Bipolar Disorder Consortium, DePaulo, J. R., Gershon, E. S., McMahon, F. J., & Potash, J. B.
- Affiliations
- Johns Hopkins University (US)
- University of Chicago (US)
- National Institutes of Health (US)
- Corresponding author
- Potash, J.B.
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2010-02-18
- Volume
- 153B
- Issue
- 2
- Pages
- 549-553
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC3032172
- OpenAlex
- W2032691461
- Cited by
- 67
- References
- 36
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 2 · 2013: 3 · 2012: 9
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K99MH086049, K01MH072866)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- reelin, bipolar disorder, sex-specific genetic association, transmission disequilibrium test, family-based association, genetic susceptibility, tag SNPs
- MeSH terms
- Reelin Protein, Alleles, Bipolar Disorder, Family Health, Female, Genetic Markers, Genotype, Humans, Male, Models, Genetic, Nerve Tissue Proteins, Neurons, Quality Control, Risk Factors, Schizophrenia, Serine Endopeptidases, Sex Factors, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins
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