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

A. Yosifova, T. Mushiroda, Michiaki Kubo, A. Takahashi, Y. Kamatani, N. Kamatani, D. Stoianov, R. Vazharova, S. Karachanak, I. Zaharieva, I. Dimova, S. Hadjidekova, V. Milanova, N. Madjirova, I. Gerdjikov, T. Tolev, N. Poryazova, M. C. O'Donovan, M. J. Owen, G. KirovD. Toncheva, Y. Nakamura

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)789-797
Number of pages9
JournalGenes, Brain and Behavior
Volume10
Issue number7
DOIs
Publication statusPublished - 01-10-2011
Externally publishedYes

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Genome-Wide Association Study
Bipolar Disorder
Single Nucleotide Polymorphism
Population
Odds Ratio
Genome
Confidence Intervals
Psychiatry

All Science Journal Classification (ASJC) codes

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Yosifova, A., Mushiroda, T., Kubo, M., Takahashi, A., Kamatani, Y., Kamatani, N., ... Nakamura, Y. (2011). Genome-wide association study on bipolar disorder in the Bulgarian population. Genes, Brain and Behavior, 10(7), 789-797. https://doi.org/10.1111/j.1601-183X.2011.00721.x
Yosifova, A. ; Mushiroda, T. ; Kubo, Michiaki ; 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, M. C. ; Owen, M. J. ; Kirov, G. ; Toncheva, D. ; Nakamura, Y. / Genome-wide association study on bipolar disorder in the Bulgarian population. In: Genes, Brain and Behavior. 2011 ; Vol. 10, No. 7. pp. 789-797.
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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, MC, Owen, MJ, Kirov, G, Toncheva, D & Nakamura, Y 2011, 'Genome-wide association study on bipolar disorder in the Bulgarian population', Genes, Brain and Behavior, vol. 10, no. 7, pp. 789-797. https://doi.org/10.1111/j.1601-183X.2011.00721.x

Genome-wide association study on bipolar disorder in the Bulgarian population. / Yosifova, A.; Mushiroda, T.; Kubo, Michiaki; 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, M. C.; Owen, M. J.; Kirov, G.; Toncheva, D.; Nakamura, Y.

In: Genes, Brain and Behavior, Vol. 10, No. 7, 01.10.2011, p. 789-797.

Research output: Contribution to journalArticle

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AU - Yosifova, A.

AU - Mushiroda, T.

AU - Kubo, Michiaki

AU - Takahashi, A.

AU - Kamatani, Y.

AU - Kamatani, N.

AU - Stoianov, D.

AU - Vazharova, R.

AU - Karachanak, S.

AU - Zaharieva, I.

AU - Dimova, I.

AU - Hadjidekova, S.

AU - Milanova, V.

AU - Madjirova, N.

AU - Gerdjikov, I.

AU - Tolev, T.

AU - Poryazova, N.

AU - O'Donovan, M. C.

AU - Owen, M. J.

AU - Kirov, G.

AU - Toncheva, D.

AU - Nakamura, Y.

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N2 - 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.

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