Genetic factors in the etiology of bipolar disorder

Consuelo Walss-Bass

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations


Traditional epidemiological studies of families, including twin and adoption studies, that quantify the degree of heritability or familial aggregation of a disease have long established that genetic inheritance is a major risk factor in the development of bipolar disorder, reporting the heritability of the disorder to be between 80 and 90%, depending on the specific diagnostic classification used (Craddock and Forty, 2006). These studies clearly established the existence of bipolar disorder susceptibility genes, showing that risk for the disorder increases the closer the relationship to the affected individual, so that a monozygotic co-twin bears the highest risk, with evidence of concordance ranging between 45 and 75%. This imperfect concordance rate reveals that being born with a set of mutated genes is not a de facto sentence of having the disorder, but merely confers susceptibility to the illness. Therefore, non-shared environmental factors likely play an important role in modulating this risk and leading to development of the illness. Perhaps understandably, because of the great contribution of genetic factors towards disease risk, most of the effort towards discerning the etiology of bipolar disorder has focused on identifying susceptibility genes, and thus the role of the environment in regulating gene function and thereby modulating risk has until recently received only broad attention. Paradoxically, despite the great efforts, genetic epidemiological studies in the last 30 years, aiming to determine the genomic location and identity of the putative causative genes, have provided inconclusive results, with no single gene currently identified as being definitively involved in the development of bipolar disorder. These studies have, however, yielded agreement on at least one major ideology: bipolar disorder is a complex polygenic disorder caused most likely by the presence of multiple susceptibility alleles (genetic variations), each of small effect that in and of themselves cause subtle cellular and physiological abnormalities, or by the presence of one or two genetic mutations of large effect which significantly disrupt chromosome structure and brain function, or a combination of mutations of both small and large effect. The additive effect of these mutations may result in certain behaviors and traits that when combined with particular environmental factors lead to a specific clinical manifestation.

Original languageEnglish (US)
Title of host publicationBipolar Disorders
Subtitle of host publicationBasic Mechanisms and Therapeutic Implications, Third Edition
PublisherCambridge University Press
Number of pages25
ISBN (Electronic)9781107477278
ISBN (Print)9781107062719
StatePublished - Jan 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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