An apparently dominant bipolar affective disorder (BPAD) locus on chromosome 20p11.2-q11.2 in a large Turkish pedigree

Bipolar affective disorder (BPAD), also known as manic-depressive illness, is a common complex, polygenic disorder characterised by recurrent cyclic e pisodes of mania and depression. Family, twin, and adoption studies strongl y suggest a genetic predisposition/susceptibility to BPAD, but no genes hav e yet been Identified. We studied a large Turkish pedigree, with an apparen tly autosomal dominant BPAD, which contained 13 affected individuals. The a ge of onset ranged from 15-40 with a mean of 25 years. The phenotypes consi sted of recurrent manic and major depressive episodes, including suicidal a ttempts; there was usually full remission with lithium treatment. A genome- wide linkage analysis using a dominant mode of inheritance showed strong ev idence for a BPAD susceptibility locus on chromosome 20p11.2-q11.2. The hig hest a-point lod score of 4.34 at theta = 0 was obtained with markers D20S6 04, D20S470, D20S836 and D20S838 using a dominant model with full penetranc e. Haplotype analysis enabled the mapping of the BPAD locus in this family between markers D20S186 and D20S109, to a region of approximately 42 cM.