Identification of susceptibility loci at 7q31 and 9p13 for bipolar disorder in an isolated population.
We performed a linkage analysis on 23 Finnish families with bipolar disorder and originating from the North-Eastern region of Finland, using the Illumina Linkage Panel IV (6K) Array with an average intermarker spacing of 0.65 cM across the genome. We detected genome-wide significant evidence for linkage of mood disorder (bipolar disorder type I, II, or not otherwise specified, manic type of schizoaffective psychosis, cyclothymia, or recurrent depression) to chromosomes 7q31 (LOD = 3.20) and 9p13.1 (LOD = 4.02). Analyzing the best markers on the complete set of 179 Finnish bipolar families supported the findings on chromosome 9p13 (maximum LOD score of 3.02 at position 383 Mb, immediately upstream of the centromere). This region harbors several interesting candidate genes, including contactin associated protein-like 3 (CNTNAP3) and aldehyde dehydrogenase 1 (ALDH1B1). For the 7q31 locus, only one extended pedigree and ten families originating from the same late settlement region in North-Eastern Finland provided evidence for linkage, suggesting that a gene predisposing to bipolar disorder is enriched in that region. Candidate genes of interest in this locus include potassium-voltage-gated channel, member 2 (KCND2) and calcium-dependent activator protein for secretion 2 (CADPS2). The loci on the centromeric region of 9p13 and the telomeric region of 7q31 may represent susceptibility loci for mood disorder in the Finnish population.
FIMM, Institute for Molecular Medicine and National Institute for Health and Welfare, Helsinki, Finland.
Outi M
OM
Palo
Pia
P
Soronen
Kaisa
K
Silander
Teppo
T
Varilo
Katja
K
Tuononen
Tuula
T
Kieseppä
Timo
T
Partonen
Jouko
J
Lönnqvist
Tiina
T
Paunio
Leena
L
Peltonen
D001714:Bipolar Disorder / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004641:Emigration and Immigration; D005190:Family; D005387:Finland; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005843:Geography; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics*