Genome Scan for Susceptibility Loci for Schizophrenia

Abstract

Objective: Schizophrenia is a relatively common, often chronic and debilitating mental illness. Evidence from various studies has clearly demonstrated that genetic factors contribute substantially to the etiology. The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. Methods: A genome-wide map of 388 microsatellite DNA markers was genotyped in 5 schizophrenia families. Nonparametric linkage analysis (Genehunter) was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. Results: Nonparametric linkage scores did not reach a genome-wide level of statistical significance (p < 0.00002) or a p value suggestive of linkage (p < 0.007) for any marker; however, one p value suggested replicated linkage (p < 0.01) at chromosome 6p24 in region D6S309 (p = 0.0047). Furthermore, 11 markers resulted in p < 0.05 at chromosomes 6p, 6q, 10q, 12q and 14q. Conclusions: Despite the differences in diagnostic schemes, in markers used and methods of analyses between studies published so far, we think that our result supports the notion that there is possibly some consistent evidence for replicated linkage of a schizophrenia susceptibility locus around the region of D6S309 at chromosome 6p24.

Excitement and confusion on chromosome 6q: the challenges of neuropsychiatric genetics in microcosm

“…26,39 Support for this focus also comes from linkage and association studies in BPD 38,48,49 and from a meta-analysis of linkage studies in BPD 5 as well as from the presence of AHI1, a gene causing a severe neuropsychiatric disorder (Joubert Syndrome) in this location. Weaker positive results in linkage studies of SCZ and BPD were also demonstrated distal to this focus 28,40,47 and may represent poorer localization of the same locus. Suggestive evidence for linkage distal to F-4 was also demonstrated for a modifier gene in Huntington's disease.…”

“…The first focus (from proximal to distal) of interest on chromosome 6q (F-1) is centered at 96 Mb with significant results for SCZ-related disorders demonstrated by two studies, 25,27 and supported from findings in SCZ, 24,26,28,30 and for both SCZ and BPD. 39 The second focus of findings (F-2) is at 105 Mb, mainly in BPD, with one significant study 42 and several supporting studies, 37,38,46 but also studies on SCZ, 24 autism 52 and multiple sclerosis.…”

“…Williams et al 29 Bailer et al 28 same TRAR4 SNPs with SCZ in the sample that yielded a very significant LOD score at this location (Amann et al). 34 A pioneer work in proteomics has also pointed to the role of genes on chromosome 6q in SCZ.…”

“…These were combined with five pedigrees, in which patients had diagnoses of SCZ spectrum disorders that were reported previously. 28 Weak evidence for linkage was demonstrated at D6S1570 (91 Mb) and D6S308 (141 Mb). The signal at D6S1570 (91 Mb) seemed to come from both subsets of pedigrees, while the more distal peak D6S308 (141 Mb) was attributed to the SCZ pedigrees.…”

Tratamento do transtorno esquizoafetivo

“…Algumas regiões são relatadas como positivas para linkage em relação à esquizofrenia sobreposta a regiões de positividade para transtornos afetivos: 18p11.2 (Schwab, 1998); 13q32 (Blouin, 1998), 22q11 (Kelsoe, 2001) e 3q (Bailer, 2002). Existem relatos de linkage tanto da esquizofrenia quanto do transtorno bipolar para o cromossomo 6, mas com a limitação da possibilidade de comparação dos resultados em razão do uso de marcadores e modelos diferentes (Cao et al, 1997;Bailer et al, 2000).…”