Linkage results on 11Q21‐22 in Eastern Quebec pedigrees densely affected by schizophrenia

Maziade, Michel; Raymond, Vincent; Cliche, D.; Fournier, Jean-Pierre; Caron, Catherine; Garneau, Y.; Nicole, Luc; Marcotte, Pascale; Couture, Christian; Simard, Carl; Boivin, Rodolphe; Rodrigue, C.; Boutin, Pierrette; Braekeleer, Marc De; Martínez, María; Mérette, Chantal

doi:10.1002/ajmg.1320600607

Cited by 54 publications

(31 citation statements)

References 27 publications

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“…A bestestimate lifetime DSM-IIIR or DSM-IV diagnosis was made with stringent procedures outlined in previous reports [37][38][39] . Ascertainment, diagnostic methods and genotyping procedures for microsatellite markers have also been described in detail elsewhere [19,20,[37][38][39] .…”

Section: Sample and Phenotype Descriptionmentioning

confidence: 99%

A New Strategy for Linkage Analysis under Epistasis Taking into Account Genetic Heterogeneity

et al. 2009

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Background/Aims: Epistasis, the biological interaction of multiple genes modulating their individual effects, is likely omnipresent in complex diseases, and modelling epistasis in linkage studies can help detect loci with little marginal effect and detect epistatic effects themselves. We propose a complete three-step strategy for parametric linkage analysis under epistasis and heterogeneity in extended pedigrees. Methods: (1) Loci most likely involved in epistatic interactions are pre-screened using two-locus one-marker analyses. (2) Among selected loci, linkage to each locus is evaluated conditionally on linkage information at another locus under two-locus epistatic models. Linkage statistics are maximized over a space of epistatic models to avoid misspecification of model parameters. (3) Families linked to the conditioning locus are selected to deal with heterogeneity between pairs of epistatically interacting loci and other unlinked loci. Properties of conditional linkage statistics prevent the introduction of bias. Results: Simulations reveal important gains in power to detect a locus with weak marginal effect involved in epistatic interaction. Application of our methods to schizophrenia and bipolar disorder in Eastern Quebec kindreds suggests epistasis between three locus pairs for bipolar disorder: 8p11-16p13, 15q11-16p13 and 18q12-15q11. Conclusion: These results suggest that the proposed strategy is powerful for tackling complex phenotypes involving epistasis and heterogeneity.

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Section: Sample and Phenotype Descriptionmentioning

confidence: 99%

A New Strategy for Linkage Analysis under Epistasis Taking into Account Genetic Heterogeneity

et al. 2009

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“…First, the 5‐HT3A receptor encoding gene is located at chromosome 11q23.1, which is one of the most important regions showing strong evidence for linkage to schizophrenia (Levinson et al., 1998; Maziade et al., 1995). Second, 5‐HT3A is involved in the release regulation of dopamine and other neurotransmitters including acetylcholine and gamma‐aminobutyric acid (GABA), which are thought to be the target for some antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

Successful treatment with risperidone increases 5‐HT 3A receptor gene expression in patients with paranoid schizophrenia – data from a prospective study

et al. 2017

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IntroductionThe relationship between peripheral 5‐HT3A receptor mRNA level and risperidone efficiency in paranoid schizophrenia patients is still unknown.MethodsA total 52 first‐episode and drug‐naive paranoid schizophrenia patients who were treated with risperidone and 53 matched healthy controls were enrolled. Patients were naturalistically followed up for 8 weeks. Positive and Negative Syndrome Scale (PANSS) was applied to assess symptom severity of the patients at baseline and at the end of 8th week.ResultsThere was no difference in 5‐HT3A receptor mRNA level between paranoid schizophrenia patients and healthy controls at baseline (p = .24). Among 47 patients who completed 8‐week naturalistic follow‐up, 37 were responders to risperidone treatment. 5‐HT3A receptor mRNA level of paranoid schizophrenia patients did not change in overall patients after 8‐week treatment with risperidone (p = .29). However, 5‐HT3A receptor mRNA level in responders increased significantly (p = .04), but not in nonresponders (p = .81).ConclusionsSuccessful treatment with risperidone increases 5‐HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that 5‐HT3A receptor may be involved in the mechanism of risperidone effect.

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“…Two other regions were investigated as follow-ups of our own preliminary findings suggesting an association between adult onset SZ and the DRD3 locus 14 and of a suggestive linkage between SZ and 11q21-q24. 16 We report here the first stage of our genome scan using 220 markers that covered approximately 30% of the genome. Some areas had to be covered more densely, because: (i) we sought to replicate previous findings and hence had to use the markers that formerly produced the most significant results; or (ii) we had to follow up positive linkage signals observed in the present study.…”

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confidence: 99%

A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes

et al. 2001

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We report the first stage of a genome scan of schizophrenia (SZ) and bipolar disorder (BP) covering 18 candidate chromosomal areas. In addition to testing susceptibility loci that are specific to each disorder, we tested the hypothesis that some susceptibility loci might be common to both disorders. A total of 480 individuals from 21 multigenerational pedigrees of Eastern Qué bec were evaluated by means of a consensus best-estimate diagnosis made blind to diagnoses in relatives and were genotyped with 220 microsatellite markers. Two-point and multipoint model-based linkage analyses were performed and mod scores (Z, for max Z max ) are reported. The strongest linkage signals were detected at D18S1145 (in 18q12; Z = 4.03) for BP, and at D6S334 (in 6p 22-24; Z het = 3.47; ␣ = 0.66) for SZ. Three other chromosomal areas (3q, 10p, and 21q) yielded linkage signals. Chromosomes 3p, 4p, 5p, 5q, 6q, 8p, 9q, 11q, 11p, 12q, 13q, 18p and 22q showed no evidence of linkage. The 18q12 results met the Lander and Kruglyak (1995) criterion for a genome-wide significant linkage and suggested that this susceptibility region may be shared by SZ and BP. The 6p finding provided confirmatory evidence of linkage for SZ. Our results suggest that both specific and common susceptibility loci must be searched for SZ and BP. Molecular Psychiatry (2001) 6, 684-693.Keywords: schizophrenia; bipolar disorder; linkage analysis; psychiatric genetics; family studies Schizophrenia (SZ) and bipolar disorder (BP) are highly heritable disorders probably involving several genes and environmental factors. 1-3 Although previous linkage studies have yielded promising results for both disorders 4-6 (see Riley and McGuffin 7 and Pulver 8 for a recent comprehensive review), their results are often conflicting and difficult to interpret. Methodological obstacles to definitive findings include insufficient statistical power, unknown mode of inheritance, populational differences, uncertain phenotype definitions, 3,9 which also complicate the comparison of results across studies. In addition, studies suggested that some susceptibility loci such as 13q32 5,6 and 18p11 5,10 might be common to both disorders. 11,12 As discussed elsewhere, 2,13,14 such common loci are compatible with previous reports of some degree of coaggregation between SZ and mood disorders. 15 In this context, as a first stage of a genome scan for SZ and BP, we prioritized chromosomal areas based on previous linkage or association results before using, in the second stage, evenly spaced (7-10 cM) markers to cover the rest of the genome which is underway. Our criteria to select candidate areas were based on previous findings of a lod score of at least 2 in the case of parametric (model-based) analyses, or a P-value of at least 0.005 in the case of non-parametric (model-free) analyses. Two other regions were investigated as follow-ups of our own preliminary findings suggesting an association between adult onset SZ and the DRD3 locus 14 and of a suggestive linkage between SZ and 11q21-q24. 16 We r...

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Linkage results on 11Q21‐22 in Eastern Quebec pedigrees densely affected by schizophrenia

Cited by 54 publications

References 27 publications

A New Strategy for Linkage Analysis under Epistasis Taking into Account Genetic Heterogeneity

A New Strategy for Linkage Analysis under Epistasis Taking into Account Genetic Heterogeneity

Successful treatment with risperidone increases 5‐HT 3A receptor gene expression in patients with paranoid schizophrenia – data from a prospective study

A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes

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