A genome scan of schizophrenia

Levinson, Douglas F.; Mahtani, Melanie M.; Brown, Donna; Nancarrow, Derek J.; Kirby, Andrew; Daly, Mark J.; Crowe, Raymond; Andreasen, Nancy C.; Silverman, J. M.; Mohs, R. C.; Endicott, Jean; Sharpe, Lawrence; Walters, Marilyn K.; Lennon, David P.; Hayward, Nicholas K.; Kruglyak, Leonid; Mowry, Bryan

doi:10.1097/00041444-199623000-00017

Cited by 96 publications

(135 citation statements)

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“…Lindholm et al 14 reported, in one very large SZ pedigree of Sweden, a lod score of 6.6 in 6q25.2 and described a 6 cM haplotype in this region segregating with the disorder. However, we 15 and others, [16][17][18][19][20][21][22] as well as a meta-analysis, 23 reported negative results in 1q21-q22, whereas two studies 24,25 provided confirmations.…”

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confidence: 55%

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families

et al. 2004

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The goal of this study was to identify susceptibility loci shared by schizophrenia (SZ) and bipolar disorder (BP), or specific to each. To this end, we performed a dense genome scan in a first sample of 21 multigenerational families of Eastern Quebec affected by SZ, BP or both (N ¼ 480 family members). This probably constitutes the first genome scan of SZ and BP that used the same ascertainment, statistical and molecular methods for the concurrent study of the two disorders. We genotyped 607 microsatellite markers of which 350 were spaced by 10 cM and 257 others were follow-up markers in positive regions at the 10 cM scan. Lander and Kruglyak thresholds were conservatively adjusted for multiple testings. We maximized the lod scores (mod score) over eight combinations (2 phenotype severity levels Â 2 models of transmission Â 2 analyses, affected/unaffected vs affected-only). We observed five genomewide significant linkages with mod score 44.0: three for BP (15q11.1, 16p12.3, 18q12-q21) and two for the shared phenotype, that is, the common locus (CL) phenotype (15q26,18q12-q21). Nine mod scores exceeded the suggestive threshold of 2.6: three for BP (3q21, 10p13, 12q23), three for SZ (6p22, 13q13, 18q21) and three for the CL phenotype (2q12.3, 13q14, 16p13). Mod scores 41.9 might represent confirmatory linkages of formerly reported genomewide significant findings such as our finding in 6p22.3 for SZ. Several regions appeared to be shared by SZ and BP. One linkage signal (15q26) appeared novel, whereas others overlapped formerly reported susceptibility regions. Despite the methodological limitations we raised, our data support the following trends: (i) results from several genome scans of SZ and BP in different populations tend to converge in specific genomic regions and (ii) some of these susceptibility regions may be shared by SZ and BP, whereas others may be specific to each. The present results support the relevance of investigating concurrently SZ and BP within the same study and have implications for the modelling of genetic effects. Molecular Psychiatry (2005) 10, 486-499.

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confidence: 55%

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families

et al. 2004

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“…However, it should be noted that for both of these family samples, genome-wide results implicated several other chromosomal regions in addition to the 2p region. Two other schizophrenia genome surveys have not found evidence of linkage to 2p markers, 34,35 though both of these groups have reported positive data for markers in the chromosome 2q centromeric region (2q11-13). In sum, additional work may be warranted in the 2p13-14 region especially using families of South Pacific or Southeast Asian ancestry.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia

et al. 1998

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A large multiplex schizophrenia pedigree ascertained from the Micronesian nation of Palau was genotyped with 406 microsatellite DNA markers evenly distributed throughout the genome. Assuming autosomal dominant inheritance, the highest genome-wide lod scores were found for DNA loci mapping to 2p13-14; the maximum lod score was 2.17 (theta = 0.05) at D2S441. A nonparametric APM analysis was also suggestive at D2S441 (APM score = 2.96, P = 0.011). Of the 14 affected cases in this extended family, eight share a large haplotype in this region spanning ෂ11 cM. When 16 other families containing 65 schizophrenic cases were typed in a follow-up study of this region, the maximum lod score remained positive (maximum at D2S441 1.69, theta = 0.20). APM results also remained positive at D2S441 for all 17 families (APM score = 4.87, P = 0.0006). The linkage and haplotype sharing results provide suggestive evidence for a 2p locus predisposing to schizophrenia in a subset of families in the Palauan population.

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“…97,144 The role of these genes in the susceptibility to schizophrenia derives added weight from a number of genetic linkage studies that confirm linkage of the disease to specific loci for these genes. 12,[145][146][147][148] Still we need more in-depth studies to completely reveal the molecular biology of schizophrenia.…”

Section: Cnp 17q21mentioning

confidence: 99%

The myelin-pathogenesis puzzle in schizophrenia: a literature review

2007

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Schizophrenia is a serious and disabling mental disorder with symptoms such as auditory hallucinations, disordered thinking and delusions, avolition, anhedonia, blunted affect and apathy. In this review article we seek to present the current scientific findings from linkage studies and susceptible genes and the pathophysiology of white matter in schizophrenia. The article has been reviewed in two parts. The first part deals with the linkage studies and susceptible genes in schizophrenia in order to have a clear-cut picture of the involvement of chromosomes and their genes in schizophrenia. The genetic linkage results seem to be replicated in some cases but in others are not. From these results, we cannot draw a fine map to a single locus or gene, leading to the conclusion that schizophrenia is not caused by a single factor/gene. In the second part of the article we present the oligodendrocyte-related genes that are associated with schizophrenia, as we hypothesize a potential role of oligodendrocyte-related genes in the pathology of the disorder.

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A genome scan of schizophrenia

Cited by 96 publications

References 0 publications

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families

Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia

The myelin-pathogenesis puzzle in schizophrenia: a literature review

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