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 (p-value = 1.33 × 10⁻⁸ calculated with the Yates-corrected χ² 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 BDNF 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 BDNF in the pathogenesis of AD.

В статье представлены результаты изучения индивидуально-психологических факторов, потенциально значимых для развития Интернет-зависимости (ИЗ), проведенного в рамках реализации российского междисциплинарного исследовательского проекта по выявлению системы маркеров высокого риска развития ИЗ. На основании полученных данных определена модель психологических предикторов ИЗ, включающая в себя личностные характеристики — высокую импульсивность планирования (как отсутствие предусмотрительности и способности следовать планам на будущее) и низкую самонаправленность (согласно психобиологической модели личности Клонинджера, отражающую недостаток осознания собственных возможностей и ограничений, отсутствие целеустремленности и ответственности). Дополнительно в число психологических предикторов вошел показатель психотравмирующего опыта детства, связанного с проживанием в сообществе с высоким уровнем насилия. Мужской пол также включен в одну из окончательных моделей как фактор риска развития ИЗ. Полученные результаты могут быть положены в основу разработки целенаправленных программ психологической помощи и профилактики ИЗ, направленных на улучшение конкретных характеристик тормозящего контроля и развитие самосознания.

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.

In several unrelated small samples examined correlation between genetic risk of chemical dependence, calculated on the basis of the contribution of geomarkers dopamine system, and phenotype of adolescents 14-17 years of age, not suffering from addiction. When genetic risk increases, the tendency to behavioural disorders increases, the tendency to abandon positive forms of self-assertion increases, the intensity of euphoria increases at the first drug samples, and the ability to predict the consequences of drug use decreases. The obtained correlations may be important for understanding the mechanism of dependence formation in adolescents with high genetic risk and development of individual prevention programs. However, these observations need to be confirmed in more representative studies.

Studied the duration of abstinence from alcohol depending on the level of genetic risk of substance abuse, calculated on the basis of the contribution of genomarkers dopamine system, the 35 adult males who abuse alcohol. It was established that the genetic risk is not associated with the duration of abstinence from alcohol in the conditions of sobriety control.