Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder
| Autor: | D T, Chen, X, Jiang, N, Akula, Y Y, Shugart, J R, Wendland, C J M, Steele, L, Kassem, J-H, Park, N, Chatterjee, S, Jamain, A, Cheng, M, Leboyer, P, Muglia, T G, Schulze, S, Cichon, M M, Nöthen, M, Rietschel, F J, McMahon, A, Farmer, P, McGuffin, I, Craig, C, Lewis, G, Hosang, S, Cohen-Woods, J B, Vincent, J L, Kennedy, Thomas G, Schulze |
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| Rok vydání: | 2011 |
| Předmět: |
Ankyrins
Male medicine.medical_specialty Bipolar Disorder Time Factors Receptors Prostaglandin Genome-wide association study Polymorphism Single Nucleotide White People 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Asian People Gene Frequency Meta-Analysis as Topic Polymorphism (computer science) Lectins medicine Humans Genetic Predisposition to Disease ANK3 Bipolar disorder RNA Messenger Psychiatry Molecular Biology Allele frequency 030304 developmental biology Cell Line Transformed 0303 health sciences Dose-Response Relationship Drug Valproic Acid Membrane Transport Proteins medicine.disease ácido valproico Antidepressive Agents Psychiatry and Mental health Gene Expression Regulation Schizophrenia Evolutionary biology Meta-analysis Cytokines Female Psychology Lithium Chloride 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Molecular psychiatry. 18(2) |
| ISSN: | 1476-5578 |
| Popis: | Meta-analyses of bipolar disorder (BD) genome-wide association studies (GWAS) have identified several genome-wide significant signals in European-ancestry samples, but so far account for little of the inherited risk. We performed a meta-analysis of ∼750,000 high-quality genetic markers on a combined sample of ∼14,000 subjects of European and Asian-ancestry (phase I). The most significant findings were further tested in an extended sample of ∼17,700 cases and controls (phase II). The results suggest novel association findings near the genes TRANK1 (LBA1), LMAN2L and PTGFR. In phase I, the most significant single nucleotide polymorphism (SNP), rs9834970 near TRANK1, was significant at the P=2.4 × 10(-11) level, with no heterogeneity. Supportive evidence for prior association findings near ANK3 and a locus on chromosome 3p21.1 was also observed. The phase II results were similar, although the heterogeneity test became significant for several SNPs. On the basis of these results and other established risk loci, we used the method developed by Park et al. to estimate the number, and the effect size distribution, of BD risk loci that could still be found by GWAS methods. We estimate that63,000 case-control samples would be needed to identify the ∼105 BD risk loci discoverable by GWAS, and that these will together explain6% of the inherited risk. These results support previous GWAS findings and identify three new candidate genes for BD. Further studies are needed to replicate these findings and may potentially lead to identification of functional variants. Sample size will remain a limiting factor in the discovery of common alleles associated with BD. |
| Databáze: | OpenAIRE |
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