Sex-specific association of the Reelin gene with bipolar disorder
| Autor: | Francis M. Mondimore, Elliot S. Gershon, James B. Potash, Peter P. Zandi, Fernando S. Goes, Virginia L. Willour, J. R. DePaulo, Francis J. McMahon, Pamela L. Belmonte, Dean F. MacKinnon, Barbara W. Schweizer |
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| Rok vydání: | 2009 |
| Předmět: |
Genetic Markers
Male Quality Control Psychosis Bipolar Disorder Genotype Offspring Cell Adhesion Molecules Neuronal Single-nucleotide polymorphism Nerve Tissue Proteins Biology Article Cellular and Molecular Neuroscience Sex Factors Risk Factors Genetic variation medicine Humans Bipolar disorder Allele Genetics (clinical) Alleles Genetics Family Health Neurons Extracellular Matrix Proteins Models Genetic Serine Endopeptidases medicine.disease Psychiatry and Mental health Reelin Protein Genetic marker Schizophrenia Female |
| Zdroj: | American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. (2) |
| ISSN: | 1552-485X |
| Popis: | 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 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 (OR(Female) = 1.79, P = 8.9 x 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. |
| Databáze: | OpenAIRE |
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