Supplementary Material for: Detection of Phenotype Modifier Genes Using Two-Locus Linkage Analysis in Complex Disorders Such as Major Psychosis
datasetposted on 14.08.2012 by Bureau A., Croteau J., Mérette C., Fournier A., Chagnon Y.C., Roy M.-A., Maziade M.
Datasets usually provide raw data for analysis. This raw data often comes in spreadsheet form, but can be any collection of data, on which analysis can be performed.
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.