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Bipolar disorder - Genetic factors

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The disorder runs in families.[1] More than two-thirds of people with bipolar disorder have at least one close relative with the disorder or with unipolar major depression, indicating that the disease has a genetic component.

Studies seeking to identify the genetic basis of bipolar disorder indicate that susceptibility stems from multiple genes. Scientists are continuing their search for these genes, using advanced genetic analytic methods and large samples of families affected by the illness. The researchers are hopeful that identification of susceptibility genes for bipolar disorder, and the brain proteins they code for, will make it possible to develop better treatments and preventive interventions targeted at the underlying illness process.


IntroductionEdit

The monozygotic concordance rate for the disorder is 70%. This means that if a person has the disorder, an identical twin has a 70% likelihood of having the disorder as well. Dizygotic twins have a 23% concordance rate. These concordance rates are not universally replicated in the literature; recent studies have shown rates of around 40% for monozygotic and <10% for dizygotic twins (see Kieseppa, 2004[2] and Cardno, 1999[3]).

In 2003, a group of American and Canadian researchers published a paper that used gene linkage techniques to identify a mutation in the GRK3 gene as a possible cause of up to 10% of cases of bipolar disorder. This gene is associated with a kinase enzyme called G protein receptor kinase 3, which appears to be involved in dopamine metabolism, and may provide a possible target for new drugs for bipolar disorder.[4]


Family studiesEdit

The role of genetic factors in bipolar disorder is indicated by concordance in monozygotic and dizygotic twins, respectively, of 57% and 14%, and the correlation between adopted people and their biological relatives (Cadoret, 1978).

Genetic mappingEdit

Studies have explored the relationship between bipolar disorder and a large number of human chromosomes:

Ongoing researchEdit

The following studies are ongoing, and are recruiting volunteers:

The Maudsley Bipolar Twin Study, based at the Institute of Psychiatry in London is conducting research about the genetic basis of bipolar disorder using twin methodology. Currently recruiting volunteers: identical and non-identical twins pairs, where either one or both twins has a diagnosis of bipolar I or II.


See alsoEdit

References & BibliographyEdit

Key textsEdit

BooksEdit

PapersEdit

Cadoret, R. J.(1978). Evidence for genetic inheritance of primary affective disorder in adoptees. Am. J. Psychiat. 135: 463-466, PMID 637144

  • Baron, M. (1977).Linkage between an X-chromosome marker (deutan color blindness) and bipolar affective illness: occurrence in the family of a lithium carbonate-responsive schizo-affective proband. Arch. Gen. Psychiat. 34: 721-725. PMID 301380
  • Baron, M., Freimer, N. F., Risch, N., Lerer, B., Alexander, J. R., Straub, R. E., Asokan, S., Das, K., Peterson, A., Amos, J., Endicott, J., Ott, J. and Gilliam, T. C.(1993).Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees. Nature Genet. 3: 49-55.

PMID 8490654

  • Baron, M., Rainer, J. D. and Risch, N. (1981).X-linkage in bipolar affective illness: perspectives on genetic heterogeneity, pedigree analysis and the X-chromosome map. J. Affect. Disorders 3: 141-157.PMID 6454708
  • Baron, M., Risch, N., Hamburger, R., Mandel, B., Kushner, S., Newman, M., Drumer, D. and Belmaker, R. H. (1987).Genetic linkage between X-chromosome markers and bipolar affective illness. Nature 326: 289-292.

PMID 3493438

PMID 1096758

  • Gejman, P. V., Detera-Wadleigh, S., Martinez, M. M., Berrettini, W. H., Goldin, L. R., Gelernter, J., Hsieh, W.-T.; Gershon, E. S. (1990). Manic depressive illness not linked to factor IX region in an independent series of pedigrees. Genomics 8: 648-655. PMID 1980485
  • Gershon, E. S., Bunney, W. E., Jr., Leckman, J. F., Van Eerdewegh, M. and De Bauche, B. A. (1976).The inheritance of affective disorders: a review of data and of hypotheses. Behavioural Genetetics 6: 227-261.

PMID 1086088

  • Gershon, E. S., Hamovit, J., Guroff, J. J., Dibble, E., Leckman, J. F., Sceery, W., Targum, S. D., Nurnberger, J. I. Goldin, L. R. and Bunney, W. E., Jr. (1982). A family study of schizo-affective, bipolar I, bipolar II, unipolar, and normal control probands. Arch. Gen. Psychiat. 39: 1157-1167 PMID 7125846
  • Hebebrand, J.(1992).A critical appraisal of X-linked bipolar illness: evidence for the assumed mode of inheritance is lacking. Brit. J. Psychiat. 160: 7-11. PMID 1544014
  • Hebebrand, J. and Hennighausen, K.(1992). A critical analysis of data presented in eight studies favouring X-linkage of bipolar illness with special emphasis on formal genetic aspects. Hum. Genet. 90: 289-293. PMID 1487243
  • Mendlewicz, J., Fleiss, J. L. and Fieve, R. R. (1972).Evidence for X-linkage in the transmission of manic-depressive illness. J.A.M.A. 222: 1624-1627.PMID 4539092
  • Mendlewicz, J.; Linkowski, P.; Wilmotte, J.(1980). Linkage between glucose-6-phosphate dehydrogenase deficiency and manic-depressive psychosis. Brit. J. Psychiat. 137: 337-342.PMID 7448473
  • Mendlewicz, J.; Rainer, J. D. (1974). Morbidity risk and genetic transmission in manic-depressive illness. Am. J. Hum. Genet. 26: 692-701.PMID 4548308
  • Mendlewicz, J.; Rainer, J. D. 1973. X-linkage in manic-depressive illness. (Letter) British Medical Journal. 3: 290.PMID 4541867
  • Mendlewicz, J., Simon, P., Sevy, S., Charon, F., Brocas, H., Legros, S., and Vassart, G. (1987). Polymorphic DNA marker on X chromosome and manic depression. Lancet I: 1230-1232,
  • Pauls, D. L. (1993). Behavioural disorders: lessons in linkage. Nature Genet. 3: 4-5.PMID 8490652
  • Reich, T. Clayton, P. J. and Winokur, G. (1969). Family history studies. V. The genetics of mania. American Journal of Psychiatry 125: 1358-1369.PMID 5304735
  • Risch, N., Baron, M. and Mendlewicz, J. (1986). Assessing the role of X-linked inheritance in bipolar-related major affective disorder. J. Psychiat. Res. 20: 275-288.PMID 3806423
  • Smeraldi, E. Negri, F. Heimbuch, R. C. and Kidd, K. K. (1981). Familial patterns and possible modes of inheritance of primary affective disorders. J. Affect. Disorders 3: 173-182.PMID 6454711
  • Thomson, P. A., Wray, N. R., Thomson, A. M., Dunbar, D. R., Grassie, M. A., Condie, A., Walker, M. T., Smith, D. J., Pulford, D. J., Muir, W., Blackwood, D. H. R., Porteous, D. J. (2005).Sex-specific association between bipolar affective disorder in women and GPR50, and X-linked orphan G protein-coupled receptor. Molec. Psychiat. 10: 470-478,
  • Winokur, G.; Tanna, V. L. (1969).Possible role of X-linked dominant factor in manic depressive disease. Dis. Nerv. Syst. 30: 89-94.PMID 4975420

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