A Genome-Wide Association Study Reveals New Genes in a Molecular Network Associated With Alcohol Dependence and Related Clinical Measures

How to cite: Levchenko, A.; Malov, S.; Antonik, A.; Protsvetkina, A.; Rybakova, K.V.; Kanapin, A.; Yakovlev, A.N.; Nenasteva, A.Y.; Nikolishin, A.E.; Cherkasov, N.; Chuprova, N.A.; Blagonravova, A.S.; Sergeeva, A.V.; Zhilyaeva, T.V.; Denisenko, M.K.; Gainetdinov, R.R.; Kibitov, A.O.; Krupitsky, A.E.M. A Genome-Wide Association Study Reveals New Genes in a Molecular Network Associated With Alcohol Dependence and Related Clinical Measures. Preprints 2022, 2022080178. https://doi.org/10.20944/preprints202208.0178.v1 Levchenko, A.; Malov, S.; Antonik, A.; Protsvetkina, A.; Rybakova, K.V.; Kanapin, A.; Yakovlev, A.N.; Nenasteva, A.Y.; Nikolishin, A.E.; Cherkasov, N.; Chuprova, N.A.; Blagonravova, A.S.; Sergeeva, A.V.; Zhilyaeva, T.V.; Denisenko, M.K.; Gainetdinov, R.R.; Kibitov, A.O.; Krupitsky, A.E.M. A Genome-Wide Association Study Reveals New Genes in a Molecular Network Associated With Alcohol Dependence and Related Clinical Measures. Preprints 2022, 2022080178. https://doi.org/10.20944/preprints202208.0178.v1

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MDPI and ACS Style

Levchenko, A.; Malov, S.; Antonik, A.; Protsvetkina, A.; Rybakova, K.V.; Kanapin, A.; Yakovlev, A.N.; Nenasteva, A.Y.; Nikolishin, A.E.; Cherkasov, N.; Chuprova, N.A.; Blagonravova, A.S.; Sergeeva, A.V.; Zhilyaeva, T.V.; Denisenko, M.K.; Gainetdinov, R.R.; Kibitov, A.O.; Krupitsky, A.E.M. A Genome-Wide Association Study Reveals New Genes in a Molecular Network Associated With Alcohol Dependence and Related Clinical Measures. Preprints 2022, 2022080178. https://doi.org/10.20944/preprints202208.0178.v1

APA Style

Levchenko, A., Malov, S., Antonik, A., Protsvetkina, A., Rybakova, K.V., Kanapin, A., Yakovlev, A.N., Nenasteva, A.Y., Nikolishin, A.E., Cherkasov, N., Chuprova, N.A., Blagonravova, A.S., Sergeeva, A.V., Zhilyaeva, T.V., Denisenko, M.K., Gainetdinov, R.R., Kibitov, A.O., & Krupitsky, A.E.M. (2022). A Genome-Wide Association Study Reveals New Genes in a Molecular Network Associated With Alcohol Dependence and Related Clinical Measures. Preprints. https://doi.org/10.20944/preprints202208.0178.v1

Chicago/Turabian Style

Levchenko, A., Alexander O. Kibitov and And Evgeny M. Krupitsky. 2022 "A Genome-Wide Association Study Reveals New Genes in a Molecular Network Associated With Alcohol Dependence and Related Clinical Measures" Preprints. https://doi.org/10.20944/preprints202208.0178.v1

Abstract

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 male and female patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33×10^-8 calculated with the Yates-corrected Chi-square 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 GWAS 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. This study indicates that a number of genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The results also suggest the genetic basis of sex-specific psychiatric comorbidities of AD.

Keywords

alcohol dependence; comorbidity; gene network; genome-wide association study; sex differences

Subject

Medicine and Pharmacology, Psychiatry and Mental Health

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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