title: Genome-wide association study on bipolar disorder in the Bulgarian population.
abstract: Bipolar disorder is a severe psychiatric disorder influenced by environmental and genetic factors. Genetic studies have implicated many variants in the disease's etiology but only few have been successfully replicated. We conducted a genome-wide association study (GWAS) on bipolar disorder in the Bulgarian population followed by a replication study of the top 100 single nucleotide polymorphisms (SNPs) showing the smallest P values. The GWAS was performed on 188 bipolar disorder patients and 376 control subjects genotyped on the Illumina 550 platform. The replication study was conducted on 122 patients and 328 controls. Although our study did not show any association P value that achieved genome-wide significance, and none of the top 100 SNPs reached the Bonferroni-corrected P value in the replication study, the plausible involvement of some variants cannot be entirely discarded. Three polymorphisms, rs8099939 [P = 2.12 × 10(-6), odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.43-2.67] in GRIK5, rs6122972 (P = 3.11 × 10(-6), OR = 2.02, 95% CI = 1.46-2.80) in PARD6B and rs2289700 (P = 9.14 × 10(-6), OR = 2.13, 95% CI = 1.53-2.95) in CTSH remained associated at a similar level after Mantel-Haenszel test for combining the results from the genome-wide and replication studies. A modest association was also detected for SNP rs1012053 (GWAS P = 4.50 × 10(-2)) in DGKH, which has already been reported as the most significant variant in a previous genome-wide scan on bipolar disorder. However, further studies using larger datasets are needed to identify variants with smaller effects that contribute to the risk of bipolar disorder.
authors.affiliation: Laboratory for International Alliance, RIKEN Center for Genomic Medicine, Suehiro-cho, Tsurumi-ku, Yokohama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yosifova
authors.forename: T
authors.initials: T
authors.lastname: Mushiroda
authors.forename: M
authors.initials: M
authors.lastname: Kubo
authors.forename: A
authors.initials: A
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kamatani
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
authors.forename: D
authors.initials: D
authors.lastname: Stoianov
authors.forename: R
authors.initials: R
authors.lastname: Vazharova
authors.forename: S
authors.initials: S
authors.lastname: Karachanak
authors.forename: I
authors.initials: I
authors.lastname: Zaharieva
authors.forename: I
authors.initials: I
authors.lastname: Dimova
authors.forename: S
authors.initials: S
authors.lastname: Hadjidekova
authors.forename: V
authors.initials: V
authors.lastname: Milanova
authors.forename: N
authors.initials: N
authors.lastname: Madjirova
authors.forename: I
authors.initials: I
authors.lastname: Gerdjikov
authors.forename: T
authors.initials: T
authors.lastname: Tolev
authors.forename: N
authors.initials: N
authors.lastname: Poryazova
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: G
authors.initials: G
authors.lastname: Kirov
authors.forename: D
authors.initials: D
authors.lastname: Toncheva
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics*; D002031:Bulgaria; D016022:Case-Control Studies; D056655:Cathepsin H / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018092:Kainic Acid Receptors / Q000235:genetics; D012016:Reference Values; D018570:Risk Assessment; D044465:White People / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056655:Cathepsin H; D018092:Kainic Acid Receptors; C511773:GRIK5 protein, human; C499657:PARD6A protein, human; C534126:CTSH protein, human