Sex-specific association of the Reelin gene with bipolar disorder.
Am J Med Genet B Neuropsychiatr Genet
; 153B(2): 549-553, 2010 Mar 05.
Article
en En
| MEDLINE
| ID: mdl-19691043
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 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trastorno Bipolar
/
Serina Endopeptidasas
/
Moléculas de Adhesión Celular Neuronal
/
Proteínas de la Matriz Extracelular
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Am J Med Genet B Neuropsychiatr Genet
Asunto de la revista:
GENETICA MEDICA
/
NEUROLOGIA
/
PSIQUIATRIA
Año:
2010
Tipo del documento:
Article