A genome-wide association study of bipolar disorder in Norwegian individuals, followed by replication in Icelandic sample.
BACKGROUND
In the present study we investigated genetic variants associated with bipolar disorder in a homogenous Norwegian sample, and potential genetic overlap with schizophrenia, using the Affymetrix 6.0 array.


METHODS
We carried out a genome-wide association study (GWAS) by genotyping 620 390 single-nucleotide polymorphisms (SNPs) in a case-control sample of Norwegian origin (the TOP study) including bipolar disorder (n=194), healthy controls (n=336) and schizophrenia (n=230), followed by replication and combined analysis in a genetically concordant Icelandic sample of bipolar disorder (n=435), and healthy controls (n=10,258).


RESULTS
We selected 1000 markers with the lowest P values in the TOP discovery GWAS and tested these (or their surrogates) for association in the Icelandic replication sample. Polymorphisms on 35 loci were confirmed associated with bipolar disorder (nominal P value<0.05; not corrected for multiple testing) in the replication sample. The most significant markers were located in DLEU2, GUCY1B2, PKIA, CCL2, CNTNAP5, DPP10, and FBN1. The combined group of schizophrenia and bipolar disorder compared to controls did not provide additional significant findings.


CONCLUSIONS
Relatively small number of samples.


CONCLUSIONS
We detected weak but reproducible association with markers in several genes, in proximity to susceptibility loci found in previous GWAS studies of bipolar disorder. Further work is required to study their localization, expression, and regulation and international meta-analytic efforts will help to further elucidate their role.
Djurovic
Srdjan
S
Institute of Psychiatry, University of Oslo, Oslo, Norway. srdjan.djurovic@medisin.uio.no
Gustafsson
Omar
O
Mattingsdal
Morten
M
Athanasiu
Lavinia
L
Bjella
Thomas
T
Tesli
Martin
M
Agartz
Ingrid
I
Lorentzen
Steinar
S
Melle
Ingrid
I
Morken
Gunnar
G
Andreassen
Ole A
OA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007055:Iceland; D008875:Middle Aged; D009664:Norway; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D055815:Young Adult
D005819:Genetic Markers