In recent years genome-wide scans and association studies for schizophrenia susceptibility genes have been published. Some have yielded significant positive findings, but there is disagreement between studies concerning their location. No mutation in any gene has yet been found. Since schizophrenia is a complex disorder, a study with sufficient power to detect a locus with small or moderate gene effect is necessary. We have thus conducted a genome-wide scan of 382 sibling pairs each with a diagnosis of schizophrenia or schizoaffective disorder. Three hundred ninety-six highly polymorphic markers spaced approximately 10 cM apart were genotyped in all individuals. Multipoint non-parametric linkage analysis was performed using MAPMAKER/SIBS to evaluate regions of the genome demonstrating increased allele sharing among affected sibling pairs as measured by a lod score. Two regions were found with multipoint maximum lod scores significant or suggestive of linkage. The highest results occurred on chromosome 10p15-p13 (peak lod score of 3.60 at D10S189) and the centromeric region of chromosome 2 (peak lod score = 2.99 at marker D2S139). No evidence of linkage was obtained at a number of locations identified in previous publications including chromosomes 1q, 4p, 5p-q, 6p, 8p, 13q, 15p and 18p. These findings on the largest genome-wide scan to date emphasize the weakness and fragility of linkage reports on schizophrenia. No linkage appears replicable across large studies. It thus has to be questioned whether the genetic contribution to this disorder is detectable by these strategies and the possibility raised that the genetic contribution may be epigenetic, i.e. related to gene expression rather than sequence variation.
|Number of pages||1|
|Journal||American Journal of Medical Genetics - Neuropsychiatric Genetics|
|Publication status||Published - 8 Oct 2001|
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience