Genome-wide linkage scan of bipolar disorder in a Colombian population isolate replicates Loci on chromosomes 7p21-22, 1p31, 16p12 and 21q21-22 and identifies a novel locus on chromosome 12q.
OBJECTIVE
Bipolar disorder (BP) is a severe psychiatric illness, characterised by alternating episodes of depression and mania, which ranks among the top ten causes of morbidity and life-long disability world-wide. We have previously performed a whole-genome linkage scan on 6 pedigrees segregating severe BP from the well-characterised population isolate of Antioquia, Colombia. We recently collected genotypes for the same set of 382 autosomal microsatellite markers in 9 additional Antioquian BP pedigrees. Here, we report the analysis of the combined pedigree set.


METHODS
Linkage analysis using both parametric and nonparametric approaches was conducted for 3 different diagnostic models: severe BP only (BPI); mood disorders (BPI, BPII and major depression); and psychosis (operationally defined by the occurrence of at least 1 episode of hallucinations and/or delusions).


CONCLUSIONS
For BPI only, the most interesting result was obtained for chromosome 7p21.1-p22.2 under a recessive model of inheritance (heterogeneity LOD score = 2.80), a region that had previously been linked to BP in a study on Portuguese Island families. For both BPI and mood disorders, nonparametric analyses identified a locus on chromosome 12ct-q14 (nonparametric linkage = 2.55 and 2.35, respectively). This locus has not previously been reported as a candidate region for BP. Additional candidate regions were found on chromosomes 1p22-31 (mood disorders) and 21q21-22 (BPI), 2 loci that have repeatedly been implicated in BP susceptibility. Linkage analysis of psychosis as a phenotype identified candidate regions on chromosomes 2q24-31 and 16p12-q12. The finding on chromosome 16p is noteworthy because the same locus has been implicated by genome-wide association analyses of BP.
Department of Genetics, Evolution and Environment, University College London, London, UK. b.kremeyer@ucl.ac.uk
B
B
Kremeyer
J
J
García
H
H
Müller
M W
MW
Burley
I
I
Herzberg
M V
MV
Parra
C
C
Duque
J
J
Vega
P
P
Montoya
M C
MC
López
G
G
Bedoya
V
V
Reus
C
C
Palacio
C
C
López
J
J
Ospina-Duque
N B
NB
Freimer
A
A
Ruiz-Linares
D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002885:Chromosomes, Human, Pair 16; D002891:Chromosomes, Human, Pair 21; D002897:Chromosomes, Human, Pair 7; D003105:Colombia; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010375:Pedigree; D055815:Young Adult