Transmission of affective disorders: An application of segregation analysis to blind family study data

Tsuang, Ming T.; Bucher, Kathleen D.; Fleming, Jerome A.; Faraone, Stephen V.

doi:10.1016/0022-3956(85)90065-2

Cited by 24 publications

(13 citation statements)

References 15 publications

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“…Finally, when genetic heterogeneity was assumed, D6S296 had the strongest evidence of linkage with schizophrenia under the recessive model, whereas D6S285 (D6S274) and D6S291 showed the strongest evidence of linkage under the dominant model. These data are compatible with the hypothesis of genetic heterogeneity of schizophrenia [Gottesman and Shields, 1982; Kendler and Diehl, 1993; Tsuang et al, 1982] and suggest the need for further study of this hypothesis.…”

Section: Discussionsupporting

confidence: 85%

“…A genetic component in the etiology of schizophrenia has been emphasized based on family, twin, and adoption studies [Cloninger, 1988; Gottesman and Shields, 1982]. The mode of inheritance is not known, however, because segregation analyses have revealed contradictory results [Kendler and Diehl, 1993; Risch and Baron, 1984; Tsuang et al, 1982]. Linkage analysis using highly polymorphic markers is an important strategy in searching for the location of potential vulnerability gene(s) of schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of linkage of markers on chromosome 6p with schizophrenia in Taiwanese families

Lin

Lee

et al. 2000

Am. J. Med. Genet.

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Previous studies have indicated possible linkage of schizophrenia with chromosome 6p21-24. In an attempt to replicate these findings, we studied the linkage of schizophrenia with nine markers on chromosome 6p21-24 in 39 Taiwanese schizophrenic nuclear families with at least two affected siblings. Two diagnostic models (narrow: Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia only; and broad: including schizophrenia, schizoaffective, and other nonaffective psychotic disorders) were used to define the disease phenotypes. With the broad and narrow diagnostic models, the marker D6S296 produced maximum two-point lod scores of 1.46 (straight theta = 0.2) and 1.35 (straight theta = 0. 2), respectively, in the recessive inheritance model. Assuming locus heterogeneity, a multipoint lod score of 0.85 was obtained between markers D6S296 and D6S277 under the narrow/recessive model. Maximum nonparametric lod scores of 1.25 ( p= 0.09) and 1.36 (p = 0.08) were observed, but still not statistically significant, at D6S296 in the narrow and broad diagnostic models, respectively. Both two-point analysis of the dominant model (lod score 0.85) and nonparametric analysis (lod score 1.25) showed a mild peak lod score appeared at marker D6S 285 as well. The results add some support to the suggestive linkage of schizophrenia with markers in the regions of chromosome 6p22 and 6p24 in an ethnically distinct Taiwanese sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:74-78, 2000.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Evaluation of linkage of markers on chromosome 6p with schizophrenia in Taiwanese families

Lin

Lee

et al. 2000

Am. J. Med. Genet.

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“…While the earlyonset form of BPI was associated with a non-Mendelian major gene transmission with polygenic background, the late-onset form of the disorder was characterized by a multifactorial transmission model. Although several segregation studies have been previously performed in bipolar disorder [Gershon et al, 1976;Goldin et al, 1983;Tsuang et al, 1985;Rice et al, 1987;Sham et al, 1991;Pauls et al, 1995;Spence et al, 1995], none of them has compared transmission patterns in early-versus late-onset probands. The study by Todd et al [1993] has previously investigated segregation models in 22 families of BPI and BPII probands with childhood and adolescent onset; in accordance with our results in families of early-onset probands, their data were compatible with a non-Mendelian major gene transmission.…”

Section: Discussionmentioning

confidence: 97%

“…Although several segregation analyses have been undertaken in BP [Gershon et al, 1976;Goldin et al, 1983;Tsuang et al, 1985;Rice et al, 1987;Sham et al, 1991;Pauls et al, 1995;Spence et al, 1995], to our knowledge, no analysis so far was concerned with comparing transmission patterns in early-versus lateonset BP. Todd et al [1993] have previously performed a segregation analysis in families of BP probands with childhood and adolescent onset, but they had no lateonset group for comparison.…”

Section: Introductionmentioning

confidence: 96%

Different familial transmission patterns in bipolar I disorder with onset before and after age 25

et al. 2001

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Gene identification in common disorders such as Alzheimer disease and breast cancer has greatly profited from the use of age of onset as criterion to delineate subgroups of disease characterized by different inheritance patterns. In bipolar affective disorder, where the majority of linkage studies have produced conflicting results, studies reporting clinical characteristics and familial occurrence of disease have suggested that age of onset might serve as an indicator for identifying more homogeneous subgroups of disease. Our study was the first to examine this hypothesis by the means of segregation analysis. We investigated a sample of 177 bipolar I probands recruited from consecutive admissions and their first- and second-degree relatives (2,407 subjects). Probands were subdivided into an early-onset (n = 107) and a late-onset group (n = 70) using an age of onset of 25 as a cut-off point. This age was chosen because the observed age of onset distribution was bimodal with a cut-off of 25 years. Morbid risks for affective disorder were found significantly higher (P = 0.01) in relatives of probands with an early onset than in probands with late onset of disease. The segregation analysis showed that the disease is transmitted differently in early- and late-onset groups. In the early-onset group, a non-Mendelian major gene with a polygenic component was favored while the data in the late-onset group were compatible with a multifactorial model. This result may have important implications for future molecular studies aiming at the identification of disease-associated genes.

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“…Family studies indicate that affective disorders, particularly bipolar affective illness, are strongly familial (Weissman, Kidd and Prusoff, 1982;Gershon et al, 1982); however, segregation analyses do not support a single mode of inheritance (Crowe et al, 1981;Goldin et al, 1983;Tsaung et al, 1985;Rice et al, 1987). Clinically, affective illnesses are heterogeneous in psychiatric comorbidity, type and pattern of symptoms and age of onset.…”

Section: Familial Transmission Of Affective Illnessmentioning

confidence: 93%

Identifying genes determining trait differences in behavior and drug response: a comment on 'Quantitative trait loci and psychopharmacology'

Goldman

Filling-Katz

1991

J Psychopharmacol

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In Plomin, McClearn and Gora-Maslak's target article (see also Science 248: 183-188, 1990), reverse genetic approaches are emphasized for locating genes determining behavioral and pharmacogenetic traits. Furthermore, prospects for such an undertaking are presented pessimistically in that behavioral traits are asserted to be polygenic (due to the simultaneous action of variant alleles at multiple loci) and are conceptualized as being determined in large part by unshared environmental factors. We disagree with Plomin et al. in three major areas and argue the following:(1) Forward genetic approaches involving candidate locus analysis and detailed analysis of the phenotype are of primary importance for isolating genes for behavioral traits, as for other genetic traits.(2) Virtually all physiologic processes and metabolic pathways involve sets of genes, resulting in genetic heterogeneity (multiple genetic origins for a trait). However, polygenicity is approximately as unusual for behavioral traits as for other traits.(3) Heritability analyses underestimate the extent to which behavioral traits are amenable to genetic analysis and have been misinterpreted to overestimate the importance of environmental factors.

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Transmission of affective disorders: An application of segregation analysis to blind family study data

Cited by 24 publications

References 15 publications

Evaluation of linkage of markers on chromosome 6p with schizophrenia in Taiwanese families

Evaluation of linkage of markers on chromosome 6p with schizophrenia in Taiwanese families

Different familial transmission patterns in bipolar I disorder with onset before and after age 25

Identifying genes determining trait differences in behavior and drug response: a comment on 'Quantitative trait loci and psychopharmacology'

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