Genetic transmission of major affective disorders: quantitative models and linkage analyses.
We comprehensively reviewed 2 types of studies aimed at specifying the mode of inheritance of major affective disorders: quantitative models and linkage analyses. Quantitative models attempt to represent the genetic mechanism responsible for the familial distribution of a disorder. Despite efforts to refine models by incorporating the bipolar-unipolar distinction or the sex effect, consistent support for a specific mode of transmission has not been found. Some mixed genetic models support single major locus inheritance, but transmission probabilities do not conform to Mendelian expectations. Linkage analysis is a more powerful technique used for testing the single gene hypothesis. Linkage results have also been inconsistent, showing moderate support for an X-linked variant of bipolar-related disorder and equivocal support for linkages to Chromosomes 6 and 11. However, relatively few genetic loci have been examined. Methodological factors, genetic heterogeneity, and phenotypic heterogeneity are discussed as potential explanations for inconsistent findings.
Faraone
S V
SV
Psychiatry Service, Brockton-West Roxbury Veterans Administration Medical Center, Massachusetts 02401.
Kremen
W S
WS
Tsuang
M T
MT
D001714:Bipolar Disorder / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D011618:Psychotic Disorders / Q000235:genetics*; D012307:Risk Factors; D012729:Sex Chromosome Aberrations / Q000235:genetics; D014960:X Chromosome