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Diagnosis-Independent Susceptibility to Major Psychiatric Disorders

Zurich Study of Nuclear Families

Based on data from 71 multiplex nuclear families (527 subjects) ascertained through an index case with a diagnosis of bipolar illness (n = 53) or schizophrenia (n = 18) we have addressed the question of diagnosis-independent susceptibility to functional psychoses. Of these subjects, 469 were genotyped for 553 polymorphisms of a genome scan along with 48 candidate genes which have been hypothesized to be involved in psychotropic drug response and to lie in genomic regions harboring vulnerability loci for functional psychoses.

Multipoint Linkage Analysis

Our search for vulnerability loci included standard multipoint linkage analysis (Allegro) along with the multivariate genetic vector space method, which allows one to detect oligogenic configurations of genomic loci and their non-linear interactions. Linkage analyses, carried out separately for the two populations of families ascertained through an index case with a diagnosis of bipolar illness and schizophrenia, yielded several genomic regions on chromosomes 1, 4, 5, 6, 11 and 22 with striking similarities between NPL-scores. Important here is the approximate parallelity of the curve characteristics rather than the absolute size of the scores (Figure).

Overlap Between Genomic Regions

Most interestingly, there was some overlap between genomic regions identified as being linked to vulnerability to functional psychoses and those identified through our study on psychotropic drug response. Multivariate analyses searching for oligogenic configurations of genomic loci that explain a major proportion of observed phenotypic variance are currently being carried out. First results indicate contributions of those genomic loci that were previously identified through our investigation into ethnicity-independent vulnerability to functional psychoses.

References

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multipoint
Fig. 10: Approximately parallel NPL score characteristics for multiplex nuclear families ascertained through an index-case with a diagnosis of bipolar illness (green) or schizophrenia (red) indicate shared vulnerability among functional psychoses.
Please note: important here is not the absolute size of the locus contributions when comparing the 2 populations ascertained through index cases with either a diagnosis of "schizophrenia" or "bipolar disorder", but the fact that the signals are showing up at the same genomic locations.
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