Search for common haplotypes on chromosome 22q in patients with schizophrenia or bipolar disorder from the Faroe...

Chromosome 22q may harbor risk genes for schizophrenia and bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. Patients with schizophrenia and bipolar affective disorder from the Faroe Islands were typed for 35 evenly distributed polymorphic markers on 22q in a search for shared risk genes in the two disorders. No single marker was strongly associated with either disease, but five two-marker segments that cluster within two regions on the chromosome have haplotypes occurring with different frequencies in patients compared to controls. Two segments were of most interest when the results of the association tests were combined with the probabilities of identity by descent of single haplotypes. For bipolar patients, the strongest evidence for a candidate region harboring a risk gene was found at a segment of at least 1.1 cM including markers D22S1161 and D22S922 (P=0.0081 in the test for association). Our results also support the a priori evidence of a susceptibility gene to schizophrenia at a segment of at least 0.45 cM including markers D22S279 and D22S276 (P=0.0075). Patients were tested for the presence of a missense mutation in the WKL1 gene encoding a putative cation channel close to segment D22S1161--D22S922, which has been associated with schizophrenia. We did not find this mutation in schizophrenic or bipolar patients or the controls from the Faroe Islands.