A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish

• Published in: Nature genetics Vol. 12; no. 4; pp. 431 - 435
• Main Authors: Ginns, Edward I, Egeland, Janice A, Paul, Steven M, Ott, Jurg, Pauls, David L, Keith, Tim P, Weissenbach, Jean, Fann, Cathy S.J, Falls, Kathleen M, Carulli, John P, Allen, Cleona R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.04.1996
• Subjects: Alleles; Biological and medical sciences; Bipolar Disorder - genetics; Chromosome Mapping; Chromosomes, Human, Pair 13 - genetics; Chromosomes, Human, Pair 15 - genetics; Chromosomes, Human, Pair 6 - genetics; Ethnic Groups - genetics; Female; Genetic Linkage; Genetic Markers; Genome, Human; Humans; Lod Score; Male; Medical sciences; Miscellaneous; Models, Genetic; Pedigree; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Techniques and methods; Genetic mapping; Human; Linkage; Genetic marker; Family study; Chromosome D13; Depression; Chromosome C6; Affective disorder; Bipolar; Gene; Chromosome D15; Risk factor; Predisposition
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0496-431

The most characteristic features of bipolar affective disorder (manic-depressive illness) are episodes of mania (bipolar I, BPI) or hypomania (bipolar II, BPII) interspersed with periods of depression. Manic-depressive illness afflicts about one percent of the population, and if untreated, is associated with an approximately 20% risk of suicide. Twin, family and adoption studies provide compelling evidence for a partial genetic aetiology, but the mode(s) of inheritance has not been identified. Nonetheless, the majority of genetic linkage studies have assumed classical mendelian inheritance attributable to a single major gene. Although segregation analyses have yielded inconsistent results (with most studies rejecting a single locus inheritance model), the best single gene model is dominant inheritance if only BPI is considered. Reported linkages of bipolar affective disorder on chromosomes 11, 18, 21 and X have been difficult to substantiate, and additional studies are required for replication or exclusion of these regions. We now present the results of our genome-wide linkage analyses that provide evidence that regions on chromosomes 6, 13 and 15 harbour susceptibility loci for bipolar affective disorder, suggesting that bipolar affective disorder in the Old Order Amish is inherited as a complex trait.