A Genome-Wide Association Study Reveals a <i>BDNF</i>-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures
At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic fu...
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2022-11-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/12/3007 |
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| author | Anastasia Levchenko Sergey Malov Alexey Antonik Anastasia Protsvetkina Kseniya V. Rybakova Alexander Kanapin Alexey N. Yakovlev Anna Y. Nenasteva Anton E. Nikolishin Nikolay Cherkasov Natalia A. Chuprova Anna S. Blagonravova Angelica V. Sergeeva Tatyana V. Zhilyaeva Maria K. Denisenko Raul R. Gainetdinov Alexander O. Kibitov Evgeny M. Krupitsky |
| author_facet | Anastasia Levchenko Sergey Malov Alexey Antonik Anastasia Protsvetkina Kseniya V. Rybakova Alexander Kanapin Alexey N. Yakovlev Anna Y. Nenasteva Anton E. Nikolishin Nikolay Cherkasov Natalia A. Chuprova Anna S. Blagonravova Angelica V. Sergeeva Tatyana V. Zhilyaeva Maria K. Denisenko Raul R. Gainetdinov Alexander O. Kibitov Evgeny M. Krupitsky |
| author_sort | Anastasia Levchenko |
| collection | DOAJ |
| description | At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (<i>p</i>-value = 1.33 × 10<sup>−8</sup> calculated with the Yates-corrected χ<sup>2</sup> test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWASs of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network, where <i>BDNF</i> is the most significant hub gene. This study indicates that several genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The study also reveals a central role of <i>BDNF</i> in the pathogenesis of AD. |
| first_indexed | 2024-03-09T17:17:57Z |
| format | Article |
| id | doaj.art-226085eda30e4e29bf156a96ef36db67 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T17:17:57Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-226085eda30e4e29bf156a96ef36db672023-11-24T13:25:05ZengMDPI AGBiomedicines2227-90592022-11-011012300710.3390/biomedicines10123007A Genome-Wide Association Study Reveals a <i>BDNF</i>-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical MeasuresAnastasia Levchenko0Sergey Malov1Alexey Antonik2Anastasia Protsvetkina3Kseniya V. Rybakova4Alexander Kanapin5Alexey N. Yakovlev6Anna Y. Nenasteva7Anton E. Nikolishin8Nikolay Cherkasov9Natalia A. Chuprova10Anna S. Blagonravova11Angelica V. Sergeeva12Tatyana V. Zhilyaeva13Maria K. Denisenko14Raul R. Gainetdinov15Alexander O. Kibitov16Evgeny M. Krupitsky17Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg 199034, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg 199034, RussiaDepartment of Geometry, Faculty of Mathematics and Mechanics, Saint Petersburg State University, Saint Petersburg 199034, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg 199034, RussiaDepartment of Addictions, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology, Saint Petersburg 192019, RussiaCenter for Computational Biology, Peter the Great Saint Petersburg Polytechnic University, Saint Petersburg 195251, RussiaLipetsk Regional Addiction Hospital, Lipetsk 398006, RussiaMoscow Research and Practical Center for Narcology of the Department of Public Health, Moscow 109390, RussiaLaboratory of Molecular Genetics, Serbsky National Medical Research Center on Psychiatry and Addictions, Moscow 119034, RussiaHuman Population Genetics Laboratory, Research Center for Medical Genetics, Moscow 115522, RussiaLaboratory of Molecular Genetics, Serbsky National Medical Research Center on Psychiatry and Addictions, Moscow 119034, RussiaPrivolzhsky Research Medical University, Nizhny Novgorod 603005, RussiaPrivolzhsky Research Medical University, Nizhny Novgorod 603005, RussiaPrivolzhsky Research Medical University, Nizhny Novgorod 603005, RussiaPrivolzhsky Research Medical University, Nizhny Novgorod 603005, RussiaInstitute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg 199034, RussiaLaboratory of Molecular Genetics, Serbsky National Medical Research Center on Psychiatry and Addictions, Moscow 119034, RussiaDepartment of Addictions, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology, Saint Petersburg 192019, RussiaAt least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (<i>p</i>-value = 1.33 × 10<sup>−8</sup> calculated with the Yates-corrected χ<sup>2</sup> test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWASs of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network, where <i>BDNF</i> is the most significant hub gene. This study indicates that several genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The study also reveals a central role of <i>BDNF</i> in the pathogenesis of AD.https://www.mdpi.com/2227-9059/10/12/3007alcohol dependence<i>BDNF</i>comorbiditygene networkgenome-wide association studysex differences |
| spellingShingle | Anastasia Levchenko Sergey Malov Alexey Antonik Anastasia Protsvetkina Kseniya V. Rybakova Alexander Kanapin Alexey N. Yakovlev Anna Y. Nenasteva Anton E. Nikolishin Nikolay Cherkasov Natalia A. Chuprova Anna S. Blagonravova Angelica V. Sergeeva Tatyana V. Zhilyaeva Maria K. Denisenko Raul R. Gainetdinov Alexander O. Kibitov Evgeny M. Krupitsky A Genome-Wide Association Study Reveals a <i>BDNF</i>-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures Biomedicines alcohol dependence <i>BDNF</i> comorbidity gene network genome-wide association study sex differences |
| title | A Genome-Wide Association Study Reveals a <i>BDNF</i>-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures |
| title_full | A Genome-Wide Association Study Reveals a <i>BDNF</i>-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures |
| title_fullStr | A Genome-Wide Association Study Reveals a <i>BDNF</i>-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures |
| title_full_unstemmed | A Genome-Wide Association Study Reveals a <i>BDNF</i>-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures |
| title_short | A Genome-Wide Association Study Reveals a <i>BDNF</i>-Centered Molecular Network Associated with Alcohol Dependence and Related Clinical Measures |
| title_sort | genome wide association study reveals a i bdnf i centered molecular network associated with alcohol dependence and related clinical measures |
| topic | alcohol dependence <i>BDNF</i> comorbidity gene network genome-wide association study sex differences |
| url | https://www.mdpi.com/2227-9059/10/12/3007 |
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