Schizophrenia spectrum disorders: an autosomal-wide scan in multiplex pedigrees

Garver, David L.; Holcomb, Jennifer; Mapua, Francesca M; Wilson, R.; Barnes, B. W.

doi:10.1016/s0920-9964(01)00157-8

Cited by 29 publications

(10 citation statements)

References 42 publications

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“…We found some evidence of a relationship of BPD with the region surrounding D1S238/D1S518 (1q31.1), which was also reported by Garver et al (2001) (D1S518; NPL 1.56, P = 0.029) for schizophrenia. In the surrounding area of our linkage signal on chromosome 4p15-16, a signal for schizophrenia was detected by Lerer et al (2003) (D4S394; NPL 2.18, P = 0.02).…”

Section: Lod Scoressupporting

confidence: 81%

Chromosome 9: linkage for borderline personality disorder features

Distel

Hottenga

Trull³

et al. 2008

Psychiatric Genetics

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Objective A large-scale twin study implicated genetic influences on borderline personality disorder (BPD) features, with a heritability estimate of 42%. To date, no genome-wide linkage study has been conducted to identify the genomic region(s) containing the quantitative trait loci that influence the manifestation of BPD features.Methods We conducted a family-based linkage study using Merlin regress. The participating families were drawn from the community-based Netherlands Twin Register. The sample consisted of 711 sibling pairs with phenotype and genotype data, and 561 additional parents with genotype data. BPD features were assessed on a quantitative scale.Results Evidence for linkage was found on chromosomes 1, 4, 9, and 18. The highest linkage peak was found on chromosome 9p at marker D9S286 with a logarithm of odds score of 3.548 (empirical P = 0.0001).Conclusion To our knowledge, this is the first linkage study on BPD features and shows that chromosome 9 is the richest candidate for genes influencing BPD.The results of this study will move the field closer to determining the genetic etiology of BPD and may have important implications for treatment programs in the future. Association studies in this region are, however, warranted to detect the actual genes.

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Section: Lod Scoressupporting

confidence: 81%

Chromosome 9: linkage for borderline personality disorder features

Distel

Hottenga

Trull³

et al. 2008

Psychiatric Genetics

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“…A linkage study of schizophrenia, schizoaffective disorder-depressed and cluster 'A' personality disorder in 30 pedigrees (77% African American, 23% Caucasian) found evidence of linkage to the same region, with a maximum nonparametric lod score of 2.55 at marker D5S426. 19,30 However, unlike these previous chromosome 5p13 findings, broad- ening the diagnosis in kindred CR02 to include psychoses and personality disorders did not increase the evidence of linkage to D5S426. Although the CVCR has developed in relative isolation, it is likely that there is a heterogeneous cause of mental illness in the population.…”

Section: Resultscontrasting

confidence: 68%

Suggestive linkage of schizophrenia to 5p13 in Costa Rica

et al. 2005

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“…It is noteworthy that numerous studies have reported linkage of SZ to the broad region spanning 8p23-21 [Blouin et al, 1998;Kaufmann et al, 1998;Brzustowicz et al, 1999;Garver et al, 2001;Gurling et al, 2001;Suarez et al, 2006]. Our smaller, 8p21 peak also lies within the ninth-ranked, weighted bin of the SZ genome scan meta-analysis [Lewis et al, 2003].…”

Section: Discussionsupporting

confidence: 52%

A reanalysis of 409 European‐Ancestry and African American schizophrenia pedigrees reveals significant linkage to 8p23.3 with evidence of locus heterogeneity

Holliday

Mowry

Nyholt

2008

American J of Med Genetics Pt B

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The detection and replication of schizophrenia risk loci can require substantial sample sizes, which has prompted various collaborative efforts for combining multiple samples. However, pooled samples may comprise sub-samples with substantial population genetic differences, including allele frequency differences. We investigated the impact of population differences via linkage reanalysis of Molecular Genetics of Schizophrenia 1 (MGS1) affected sibling-pair data, comprising two samples of distinct ancestral origin: European (EA: 263 pedigrees) and African-American (AA: 146 pedigrees). To exploit the linkage information contained within these distinct continental samples, we performed separate analyses of the individual samples, allowing for within-sample locus heterogeneity, and the pooled sample, allowing for both within-sample and between-sample heterogeneity. Significance levels, corrected for the multiple tests, were determined empirically. For all suggestive peaks, stronger linkage evidence was obtained in either the EA or AA sample than the combined sample, regardless of how heterogeneity was modeled for the latter. Notably, we report genomewide significant linkage of schizophrenia to 8p23.3 and evidence for a second, independent susceptibility locus, reaching suggestive linkage, 29 cM away on 8p21.3. We also detected suggestive linkage on chromosomes 5p13.3 and 7q36.2. Many regions showed pronounced differences in the extent of linkage between the EA and AA samples. This reanalysis highlights the potential impact of population differences upon linkage evidence in pooled data and demonstrates a useful approach for the analysis of samples drawn from distinct continental groups.

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Schizophrenia spectrum disorders: an autosomal-wide scan in multiplex pedigrees

Cited by 29 publications

References 42 publications

Chromosome 9: linkage for borderline personality disorder features

Chromosome 9: linkage for borderline personality disorder features

Suggestive linkage of schizophrenia to 5p13 in Costa Rica

A reanalysis of 409 European‐Ancestry and African American schizophrenia pedigrees reveals significant linkage to 8p23.3 with evidence of locus heterogeneity

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