title: A genome scan and follow-up study identify a bipolar disorder susceptibility locus on chromosome 1q42.
abstract: In this study, we report a genome scan for psychiatric disease susceptibility loci in 13 Scottish families. We follow up one of the linkage peaks on chromosome 1q in a substantially larger sample of 22 families affected by schizophrenia (SCZ) or bipolar affective disorder (BPAD). To minimise the effect of genetic heterogeneity, we collected mainly large extended families (average family size >18). The families collected were Scottish, carried no chromosomal abnormalities and were unrelated to the large family previously reported as segregating a balanced (1:11) translocation with major psychiatric disease. In the genome scan, we found linkage peaks with logarithm of odds (LOD) scores >1.5 on chromosomes 1q (BPAD), 3p (SCZ), 8p (SCZ), 8q (BPAD), 9q (BPAD) and 19q (SCZ). In the follow-up sample, we obtained most evidence for linkage to 1q42 in bipolar families, with a maximum (parametric) LOD of 2.63 at D1S103. Multipoint variance components linkage gave a maximum LOD of 2.77 (overall maximum LOD 2.47 after correction for multiple tests), 12 cM from the previously identified SCZ susceptibility locus DISC1. Interestingly, there was negligible evidence for linkage to 1q42 in the SCZ families. These results, together with results from a number of other recent studies, stress the importance of the 1q42 region in susceptibility to both BPAD and SCZ.
authors.affiliation: Institute of Cell, Animal and Population Biology, University of Edinburgh, Kings Buildings, Edinburgh, UK. MacgregorS@cf.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Macgregor
authors.forename: P M
authors.initials: PM
authors.lastname: Visscher
authors.forename: S A
authors.initials: SA
authors.lastname: Knott
authors.forename: P
authors.initials: P
authors.lastname: Thomson
authors.forename: D J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: J K
authors.initials: JK
authors.lastname: Millar
authors.forename: R S
authors.initials: RS
authors.lastname: Devon
authors.forename: D
authors.initials: D
authors.lastname: Blackwood
authors.forename: W J
authors.initials: WJ
authors.lastname: Muir
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats; D010375:Pedigree; D012559:Schizophrenia / Q000235:genetics*; D012606:Scotland