A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2

Abstract

Bipolar disorder is a severe mental illness characterized by mood swings of elation and depression. Family, twin, and adoption studies suggest a complex genetic etiology that may involve multiple susceptibility genes and an environmental component. To identify chromosomal loci contributing to vulnerability, we have conducted a genome-wide scan on approximately 396 individuals from 22 multiplex pedigrees by using 607 microsatellite markers. Multipoint nonparametric analysis detected the strongest evidence for linkage at 13q32 with a maximal logarithm of odds (lod) score of 3.5 (P = 0. 000028) under a phenotype model that included bipolar I, bipolar II with major depression, schizoaffective disorder, and recurrent unipolar disorder. Suggestive linkage was found on 1q31-q32 (lod = 2. 67; P = 0.00022) and 18p11.2 (lod = 2.32; P = 0.00054). Recent reports have linked schizophrenia to 13q32 and 18p11.2. Our genome scan identified other interesting regions, 7q31 (lod = 2.08; P = 0. 00099) and 22q11-q13 (lod = 2.1; P = 0.00094), and also confirmed reported linkages on 4p16, 12q23-q24, and 21q22. By comprehensive screening of the entire genome, we detected unreported loci for bipolar disorder, found support for proposed linkages, and gained evidence for the overlap of susceptibility regions for bipolar disorder and schizophrenia.