Huntington disease: Linkage analysis with age‐of‐onset corrections

Hodge, Susan E.; Spence, M. Anne; Crandall, Barbara F.; Sparkes, Robert S.; Sparkes, Maryellen C.; Crist, Michol; Tideman, Susan

doi:10.1002/ajmg.1320050305

Cited by 28 publications

(12 citation statements)

References 6 publications

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“…Our overall results are consistent with the study of Hodge et al (1980) which suggested that the exact nature of the correction for age was not critical to the establishment of linkage, so long as a reasonable adjustment was made. Methods 2 and 3 produced identical results since both approximations to the age curves were strikingly similar.…”

Section: Discussionsupporting

confidence: 93%

Analysis of Huntington disease linkage and age-of-onset distributions

1986

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Section: Discussionsupporting

confidence: 93%

Analysis of Huntington disease linkage and age-of-onset distributions

1986

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“…major depression, substance and alcohol abuse). In some cases 10,12 the analytic strategies and model parameters we used were almost identical to those in the previous reports or differed only in ways 21 unlikely to have a large effect on outcome 40 . However, in the case of the studies by Kaabi et al 9 and Thorgierssen 8 there were significant analytic differences that must be taken into account in evaluating our results.…”

Section: Discussionmentioning

confidence: 96%

Linkage analysis of alternative anxiety phenotypes in multiply affected panic disorder families

Fyer

Costa

Haghighi

et al. 2012

Psychiatric Genetics

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Background The choice of phenotype definitions for genetic studies of panic and phobic disorders is complicated by family, twin and neurobiological data indicating both distinct and shared risk factors as well as heterogeneity within categories. We previously reported a genome scan in 120 multiplex panic disorder (PD) families using a phenotype that closely adhered to the DSM IV PD definition. Here we extend this work by conducting exploratory linkage analyses in this same pedigree set using ten additional literature- based panic and phobia-related phenotypes that take into account aspects of these hypothesized complexities. Methods Multiply affected families (> 2 individuals with PD) were recruited from clinical and non-clinical sources, evaluated by clinician administered semi-structured interview and subsequent blind consensus best estimate procedure. Each phenotype was analyzed under dominant and recessive models using parametric 2-point (homogeneity and heterogeneity), multipoint, and non-parametric methods. Empirically based permutations were used to estimate model specific and global (across all phenotypes) p-values. Results The highest score was a 2-point lod (4.27, global p < 0.08) on chromosome 13 (D13S793, 76cM) for the phenotype “specific or social phobia” under a recessive model and conditions of homogeneity. There was minimal support for linkage to any of the remaining nine phenotypes. Conclusions Though interpretation of findings is limited by sample size and the large number of phenotypes and models analyzed these data suggest a region on chromosome 13 as a potential site for further exploration in relation to risk for specific and social phobias.

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“…This approach should also be used in genetic linkage studies. Hodge et al [1980] have recently reported that the shape of the distribution used for age correction is not critical in a HD linkage study as long as some age correction is made; however, they indicate (by using best fitting distribution) that the location of the distribution can be important. These results could have a significant effect on linkage, in particular, if a valid linkage relationship is found.…”

Section: Discussionmentioning

confidence: 97%

Age‐of‐onset heterogeneity in Huntington disease families

et al. 1983

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Ten Huntington disease (HD) families are analyzed using maximum likelihood methods to study age-of-onset (AO) heterogeneity. Both age of onset and age at examination are used in calculating an individual's likelihood of being affected; familial correlations and family structure are not included in the model. The model allows for differences in current age distributions by considering the distribution of age of onset conditional on age at examination. Families are grouped according to family type (ie, juvenile-onset families and adult-onset families) and then analyzed within each family type as well as between the two types, using both a chi-square test for heterogeneity and F-ratios. The results of the chi-square analyses indicate heterogeneity in AO among the individual families as well as between the two family types. However, the results of the F-ratios show no significant difference between the two family types, indicating that the difference in the chi-square analysis between the two family types is mostly owing to variation among the families. Thus, the results demonstrate that the existing variation in age of onset between these two family types is dwarfed by the magnitude of the variation among the families within each type. This implies that families of sufficient size should be evaluated individually for age-of-onset data for the purpose of either genetic counseling or linkage studies.

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Huntington disease: Linkage analysis with age‐of‐onset corrections

Cited by 28 publications

References 6 publications

Analysis of Huntington disease linkage and age-of-onset distributions

Analysis of Huntington disease linkage and age-of-onset distributions

Linkage analysis of alternative anxiety phenotypes in multiply affected panic disorder families

Age‐of‐onset heterogeneity in Huntington disease families

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