Cross-Disorder Analysis of Bipolar Risk Genes: Further Evidence of DGKH as a Risk Gene for Bipolar Disorder, but also Unipolar Depression and Adult ADHD
| Autor: | Volker Arolt, Susanne Kreiker, Henriette N. Buttenschøn, Sabine Herterich, Heike Weber, Bernhard T. Baune, Andrea Boreatti-Hümmer, Katharina Domschke, Andreas Reif, Christian Jacob, Jürgen Deckert, Alexandra Gessner, Lena Weissflog, Thuy Trang Nguyen, Silke Gross-Lesch, Juliane Kopf, Sarah Kittel-Schneider, Klaus-Peter Lesch, Julia Volkert, Maria Neuner, Ole Mors |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Diacylglycerol Kinase Bipolar Disorder Genome-wide association study Single-nucleotide polymorphism Polymorphism Single Nucleotide Risk Factors mental disorders medicine Humans SNP Genetic Predisposition to Disease ANK3 Bipolar disorder Aged Genetic association Pharmacology Genetics Depressive Disorder biology NPAS3 Haplotype Genetic Variation Middle Aged medicine.disease Psychiatry and Mental health Haplotypes Attention Deficit Disorder with Hyperactivity biology.protein Female Original Article Psychology Genome-Wide Association Study |
| Zdroj: | Weber, H, Kittel-Schneider, S, Gessner, A, Domschke, K, Neuner, M, Jacob, C P, Buttenschøn, H N, Boreatti-Hümmer, A, Volkert, J, Herterich, S, Baune, B T, Gross-Lesch, S, Kopf, J, Kreiker, S, Nguyen, T T, Weissflog, L, Arolt, V, Mors, O, Deckert, J, Lesch, K-P & Reif, A 2011, ' Cross-Disorder Analysis of Bipolar Risk Genes: Further Evidence of DGKH as a Risk Gene for Bipolar Disorder, but also Unipolar Depression and Adult ADHD ', Neuropsychopharmacology, vol. 36, no. 10, pp. 2076-2085 . https://doi.org/10.1038/npp.2011.98 |
| ISSN: | 1740-634X 0893-133X |
| DOI: | 10.1038/npp.2011.98 |
| Popis: | Recently, several genome-wide association studies (GWAS) on bipolar disorder (BPD) suggested novel risk genes. However, only few of them were followed up and further, the specificity of these genes is even more elusive. To address these issues, we genotyped SNPs in ANK3, CACNA1C, CMTM8, DGKH, EGFR, and NPAS3, which were significantly associated with BPD in previous GWAS, in a sample of 380 BPD patients. Replicated SNPs were then followed up in patients suffering from unipolar depression (UPD; n=387) or adult attention-deficit/hyperactivity disorder (aADHD; n=535). While we could not confirm an association of ANK3, CACNA1C, and EGFR with BPD, 10 SNPs in DGKH, CMTM8, and NPAS3 were nominally associated with disease, with two DGKH markers surviving correction for multiple testing. When these were followed up in UPD and aADHD, seven DGKH SNPs were also associated with UPD, while one SNP each in NPAS3 and CMTM8 and four in DGKH were linked to aADHD. Furthermore, a DGKH haplotype consisting of rs994856/rs9525580/rs9525584 GAT was associated with all disorders tested, while the complementary AGC haplotype was protective. The corresponding haploblock spans a 27-kb region covering exons coding for amino acids 65-243, and thus might include functional variants yet to be identified. We demonstrate an association of DGKH with BPD, UPD, and aADHD by applying a two-stage design. These disorders share the feature of mood instability, so that this phenotype might be associated with genetic variation in DGKH.Neuropsychopharmacology advance online publication, 8 June 2011; doi:10.1038/npp.2011.98. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|