A combined analysis of D22S278 marker alleles in affected sib-pairs: Support for a susceptibility locus for schizophrenia at chromosome 22q12

Abstract

Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets (Vallada et al., Am J Med Genet 60:139‐146, 1995; Polymeropoulos et al., Neuropsychiatr Genet 54:93‐99, 1994; Lasseter et al., Am J Med Genet, 60:172‐173, 1995). Using the affected sib‐pair method as implemented by the program ESPA, the combined dataset showed 252 alleles shared compared with 188 alleles not shared (chi‐square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib‐pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi‐square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib‐pair analysis was used. These results indicate that there may be a susceptibility locus for schizophrenia at 22q12. © 1996 Wiley‐Liss, Inc.

The phenotypes of bipolar disorder: relevance for genetic investigations

“…12,13,19,20,[60][61][62] They are especially interesting as the same regions may encompass susceptibility genes for schizophrenia. [63][64][65][66][67][68][69][70] Park et al 71 made similar conclusions in a study of psychotic BD in which most areas of linkage overlapped with those reported in previous investigations of schizophrenia.…”

Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia

“…23 The newly discovered synapsin III gene might be a candidate molecule in schizophrenia, 25,26 because of the role of synapsins in neurotransmitter release and synaptogenesis. Reported linkage studies in affected sib pairs showed a hot spot about 4.5 cM from the syn-apsin III gene on chromosome 22, 27 and the region on 22q12 is also associated with the phenotypic measures of inhibitory neurophysiological functioning, P50 auditory sensory gating, and antisaccade ocular motor performance. 28 We tested whether synapsin might also be decreased in the hippocampal formation of schizophrenia using an antibody that measures synapsin Ia, IIa, and IIIa proteins.…”

Genome-wide scans of three independent sets of 90 Irish multiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes

“…In parallel to these two major developments, incremental but important progress has been made due to the coordination of genome-wide scans with more targeted replication studies of promising regions by worldwide consortia. [12][13][14][15] Many regions now have support from multiple independent studies, although due to major methodological differences between studies, the cumulative strength of the evidence for each locus remains difficult to judge. Recent reviews, [16][17][18][19][20] when taken together, provide a fairly comprehensive catalog of the most positive studies, but it is likely that negative results are substantially under-represented in the literature.…”