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Genome-wide association study on bipolar disorder in the Bulgarian population

Yosifova, A., Mushiroda, T., Kubo, M., Takahashi, A., Kamatani, Y., Kamatani, N., Stoianov, D., Vazharova, R., Karachanak, S., Zaharieva, I., Dimova, I., Hadjidekova, S., Milanova, V., Madjirova, N., Gerdjikov, I., Tolev, T., Poryazova, N., O'Donovan, Michael Conlon, Owen, Michael John, Kirov, George, Toncheva, D. and Nakamura, Y. 2011. Genome-wide association study on bipolar disorder in the Bulgarian population. Genes, Brain and Behavior 10 (7) , pp. 789-797. 10.1111/j.1601-183X.2011.00721.x

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Bipolar affective disorder; DGKH; genome-wide association study; GRIK5; single nucleotide polymorphism
Publisher: Wiley-Blackwell
ISSN: 1601-1848
Last Modified: 04 Jun 2017 03:50
URI: http://orca.cf.ac.uk/id/eprint/27692

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