Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease

Abstract

The difficulties in defining the borders of the schizophrenia spectrum is one major source of variance in linkage studies of schizophrenia. The employment of biological markers may prove advantageous. Due to empirical evidence, eye tracking dysfunction (ETD) has been discussed to be the most promising marker for genetic liability to schizophrenia. With respect to the recent progress in genomic scans, which have pointed to the short arm of chromosome 6, we carried out a scan of the 6p21-23 region with 16 microsatellite markers to test for linkage between chromosomal markers and ETD as well as schizophrenia. We tested 5 models of inheritance of ETD and found maximum two-point lod scores of 3.51 for D6S271 and 3.44 for D6S282. By including these markers in a multipoint analysis, a lod score of 4.02 was obtained. In the case of schizophrenia, 7 models were tested; however, with non-significant results. Our findings, together with another recent linkage report, point to the possibility of a second susceptibility locus for schizophrenia which may be located centromeric to the HLA region. Also, the evidence of ETD being a susceptibility marker for schizophrenia receives further support.

Platelet Serotonergic Markers as Endophenotypes for Obsessive-Compulsive Disorder

“…For example, the QT elongation on electrocardiogram was used to discover the genes underlying the long QT syndrome, characterized by syncope, ventricle arrhythmias, and sudden death (Keating and Sanguinetti, 2001). In the field of psychiatry, disturbances of P50 auditory evoked response and smooth pursuit eye movements are among the best established endophenotypes present in schizophrenic patients and their unaffected relatives, and linkage studies have already identified the loci involved in chromosome 15q (Freedman et al, 1997) and 6p (Arolt et al, 1996), respectively. In OCD, stratification by 5-HT level could decrease genetic heterogeneity and increase power to identify susceptibility genes in association and linkage studies.…”

The Evolution of Drug Development in Schizophrenia: Past Issues and Future Opportunities

“…Two independent studies found significant linkage of eye tracking phenotype to loci on chromosome 6p21 (Arolt et al, 1996;Matthysse et al, 2004). Association with COMT and DRD3 genes reported (Thaker et al, 2004;Rybakowski et al, 2001).…”

Tumor necrosis factor promoter haplotype associated with schizophrenia reveals a linked locus on 1q44

“…47,48 In light of the immunological theory of schizophrenia, the MHC has long been proposed as a candidate locus that may influence the susceptibility to schizophrenia. The MHC spans approximately 4 million base pairs of DNA and has been mapped to 9 Linkage studies have also suggested that there may be at least one locus on chromosome 6p that affects susceptibility to schizophrenia, [10][11][12][13][14] eye-tracking dysfunction, 15 and/or the severity of positive symptoms. 16 There are many genes of potential interest in MHC region that demonstrated association with schizophrenia phenotypes in previous studies-NOTCH4, [49][50][51][52] TNXB, 53 DRB1, 54-57 DQB1.…”

“…9 Linkage studies also suggest there may be one or more loci on chromosome 6p that affect susceptibility to schizophrenia. [10][11][12][13][14] In addition, there is some evidence that genetic loci on chromosome 6p may influence the manifestation of the endophenotype of eye-tracking dysfunction 15 and modify the severity of positive symptoms in affected subjects. 16 An example of the utility of stratifying linkage data set on the basis of HLA genotypes (DR3 and DR4) was demonstrated in the successful identification of a causative locus for Type I diabetes mellitus on chromosome 11q, 17 a finding that was confirmed by other linkage 18,19 and linkage disequilibrium studies.…”