The transmission of manic depressive illness—II. Segregation analysis of three sets of family data

Bucher, Kathleen D.; Elston, Robert C.; Green, Ronald; Whybrow, Peter C.; Helzer, John E.; Reich, Theodore; Clayton, Paula J.; Winokur, George

doi:10.1016/0022-3956(81)90014-5

Cited by 38 publications

(13 citation statements)

References 11 publications

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“…Fi nally, Bucher et al (1981) reported that a segregation analysis of three sets of data indicated that neither an X-linked nor an autosomal dominant gene can account fo r the transmission of BPD. Three of the studies were compatible with a sex-threshhold model and one compatible with a sex-linkage model.…”

Section: Affective Disordersmentioning

confidence: 99%

Human Behavior Genetics

Henderson

1982

Annu. Rev. Psychol.

219

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Section: Affective Disordersmentioning

confidence: 99%

Human Behavior Genetics

Henderson

1982

Annu. Rev. Psychol.

219

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“…We have also noted that similar estimates of the major locus parameters (q and t) and the transmission frequencies are obtained, whether joint or conditional likelihood is considered. Thus the rejection of the Mendelian transmission hypothesis, as reported in previous analyses of affective disorders, might be the result of mechanisms other than those considered here, such as more complex sources of environmental resemblance or a possible genetic heterogeneity [Bucher et al, 1981;Goldin et al, 1983;Rice et al, 19871. We are planning similar studies, considering other types of environmental familial correlation. It will also be interesting to assess how the unified and newly developed models, mentioned in the Introduction, may permit us to determine the role of genetic factors when the environmental effects are measured.…”

Section: Discussionmentioning

confidence: 58%

Robustness of the unified model to shared environmental effects in the analysis of dichotomous traits

Demenais

Abel

1989

Genetic Epidemiology

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Simulation studies were conducted to assess to what extent the conclusions of segregation analysis, performed under the unified model, can be affected by the presence of unmeasured environmental factors shared by family members. Dichotomous data were generated on six-member nuclear families under two variants of the mixed model, incorporating environmental effects shared by all family members. When the generating model includes a polygenic component and a shared environmental effect, there is false detection of a major gene, especially when the joint likelihood of parents' and offspring's phenotypes is computed. The proportion of false conclusions increases as the shared environmental effect increases. On the other hand, the presence of a shared environmental effect in addition to a major gene component does not alter the detection of the major gene nor the transmission probability estimates, which are close to the expected Mendelian values. The rejection of the Mendelian transmission hypothesis, as observed in familial analyses of affected disorders, might be the result of mechanisms other than those considered here, such as more complex sources of environmental resemblance or a possible genetic heterogeneity.

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“…Some segregation analyses on systematically ascertained pedigree sets have produced results consistent with single gene models, 27 30 54 55 while others have been unable to show major locus transmission. [56][57][58] However, caution is required in interpreting these results because of the limited power of the studies to distinguish between single gene and oligogenic models and because of the failure to take account of an important parameter, the recurrence risk in MZ cotwins of a bipolar proband. 59 The observed very rapid decrease in recurrence risk from identical co-twins to first degree relatives and back to the general population (as shown in table 2) is not consistent with single gene modes of inheritance.…”

Section: Mode Of Inheritancementioning

confidence: 99%

Genetics of bipolar disorder

Craddock¹,

Russell²

2006

Beyond Nature and Nurture in Psychiatry

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Bipolar disorder (also known as manic depressive illness) is a complex genetic disorder in which the core feature is pathological disturbance in mood (aVect) ranging from extreme elation, or mania, to severe depression usually accompanied by disturbances in thinking and behaviour. The lifetime prevalence of 1% is similar in males and females and family, twin, and adoption studies provide robust evidence for a major genetic contribution to risk. There are methodological impediments to precise quantification, but the approximate lifetime risk of bipolar disorder in relatives of a bipolar proband are: monozygotic co-twin 40-70%; first degree relative 5-10%; unrelated person 0.5-1.5%. Occasional families may exist in which a single gene plays the major role in determining susceptibility, but the majority of bipolar disorder involves the interaction of multiple genes (epistasis) or more complex genetic mechanisms (such as dynamic mutation or imprinting). Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest identified in linkage studies include 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Chromosome 18 is also of interest but the findings are confusing with up to three possible regions implicated. To date most candidate gene studies have focused on neurotransmitter systems influenced by medication used in clinical management of the disorder but no robust positive findings have yet emerged. It is, however, almost certain that over the next few years bipolar susceptibility genes will be identified. This will have a major impact on our understanding of disease pathophysiology and will provide important opportunities to investigate the interaction between genetic and environmental factors involved in pathogenesis. This is likely to lead to major improvements in treatment and patient care but will also raise important ethical issues that will need to be addressed. (J Med Genet 1999;36:585-594)

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The transmission of manic depressive illness—II. Segregation analysis of three sets of family data

Cited by 38 publications

References 11 publications

Human Behavior Genetics

Human Behavior Genetics

Robustness of the unified model to shared environmental effects in the analysis of dichotomous traits

Genetics of bipolar disorder

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