Detection of phenotype modifier genes using two-locus linkage analysis in complex disorders such as major psychosis.
Hum Hered
; 73(4): 195-207, 2012.
Article
em En
| MEDLINE
| ID: mdl-22907187
ABSTRACT
OBJECTIVE:
To increase power to detect modifier loci conferring susceptibility to specific phenotypes such as disease diagnoses which are part of a broader disorder spectrum by jointly modeling a modifier and a broad susceptibility gene and to identify modifier loci conferring specific susceptibility to schizophrenia (SZ) or to bipolar disorder (BP) using the approach.METHODS:
We implemented a two-locus linkage analysis model where a gene 1 genotype increases the risk of a broad phenotype and a gene 2 genotype modifies the expression of gene 1 by conferring susceptibility to a specific phenotype.RESULTS:
Compared to a single-locus analysis within the broad phenotype, the proposed approach had greater power to detect the modifier gene 2 (0.96 vs. 0.54 under a simulation scenario including heterogeneity). In a sample of 12 mixed SZ and BP Eastern Quebec kindreds, D8S1110 at 8p22 showed the strongest evidence of linkage to a gene determining a specific phenotype (SZ or BP) among subjects susceptible to major psychosis because of putative genes at 10p13 (D10S245, conditional maximized LOD (cMOD) = 4.20, p = 0.0003) and 3q21-q23 (D3S2418, cMOD = 4.09, p = 0.0005).CONCLUSION:
The proposed strategy is useful to detect modifier loci conferring susceptibility to a specific phenotype within a broader phenotype.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Transtornos Psicóticos
/
Esquizofrenia
/
Transtorno Bipolar
/
Genes Modificadores
/
Ligação Genética
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Hered
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Canadá