Mendelian randomization integrating GWAS and eQTL data revealed genes pleiotropically associated with major depressive disorder
| Autor: | Xiaohan Yang, Huiquan Jing, Huarong Yang, Wenjin Lu, Di Liu, Bowen Feng, Weizhu Zhou, Minglu Xu, Jingyun Yang, Chuntao Zhao |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Quantitative Trait Loci Neurosciences. Biological psychiatry. Neuropsychiatry Genome-wide association study Computational biology Biology Quantitative trait locus Molecular neuroscience Major histocompatibility complex Polymorphism Single Nucleotide Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine mental disorders Mendelian randomization medicine Humans Genetic Predisposition to Disease Gene Biological Psychiatry Genetic association Depressive Disorder Major Mechanism (biology) Comparative genomics Mendelian Randomization Analysis medicine.disease Psychiatry and Mental health 030104 developmental biology Multiple comparisons problem Expression quantitative trait loci biology.protein Major depressive disorder 030217 neurology & neurosurgery RC321-571 Genome-Wide Association Study |
| Zdroj: | Translational Psychiatry Translational Psychiatry, Vol 11, Iss 1, Pp 1-9 (2021) |
| ISSN: | 2158-3188 |
| Popis: | ObjectivesTo prioritize genes that are pleiotropically or potentially causally associated with the risk of MDD.MethodsWe applied the summary data-based Mendelian randomization (SMR) method integrating GWAS and expression quantitative trait loci (eQTL) data in 13 brain regions to identify genes that were pleiotropically associated with the risk of MDD. In addition, we repeated the analysis by using the meta-analyzed version of the eQTL summary data in the brain (brain-eMeta).ResultsWe identified multiple significant genes across different brain regions that may be involved in the pathogenesis of MDD. The prime-specific gene BTN3A2 (corresponding probe: ENSG00000186470.9) was the top hit showing pleotropic association with MDD in 9 of the 13 brain regions and in brain-eMeta, after correction for multiple testing. Many of the identified genes are located in the human major histocompatibility complex (MHC) region on chromosome 6 and are mainly involved in immune response.ConclusionsOur SMR analysis revealed that multiple genes showed pleiotropic association with MDD across the brain regions. These findings provide important leads to a better understanding of the mechanism of MDD, and reveals potential therapeutic targets for the prevention and effective treatment of MDD. |
| Databáze: | OpenAIRE |
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