engleski

Composite neurocognitive phenotype correlated with schizophrenia: A grade of membership model and genetic linkage findings

We demonstrate a novel method for constructing composite quantitative phenotypes for QTL analysis in schizophrenia. In 124 patients, 202 first-degree relatives, and 71 controls, a neurocognitive battery identified deficits (2 SD below the mean of the controls) in attention, verbal fluency, IQ and speed of processing in 62% of patients, 36 % of relatives and 7% of controls (p<0.001). We applied Grade of Membership (GoM) analysis to resolve heterogeneity and integrated the outcomes of all measures used in to 5 pure types of deficit. Patterns of deficit were found to aggregate in families and correlate with personality traits as measured by Cloninger&#8217; s TCI and Raine&#8217; s SPQ. Two of the pure types had joint heritability of 0.39, p=0.003. We genotyped 72 families (311 subjects) with markers spanning a region on chromosome 6 where positive lod scores have been reported (Schwab et al 1995). Using linear combination of GoM scores, we constructed a phenotype for variance component linkage analysis (SOLAR program, Almasy and Blangero 1998). We repeated the analysis using a single test (CPT-IP) as quantitative trait. Multipoint linkage using the GoM phenotype yielded a maximum lod score of 2.24, as compared to a lod score of 0.6 when using CPT-IP.

schizophrenia; endopheotype; linkage analysis; grade of membership

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