Genetics of alcohol use disorder: a review
Genetics of alcohol use disorder: a review
A review by Lesch (2005) focuses on serotonin as a link between alcoholism genetics and environment. Based on endophenotypes such as response to ethanol or reaction to stress and anxiety, the authors discuss the role that the serotinergic system plays in modifying each step of the biological hierarchy from genetic basic studies of variants of serotonin to molecular functional imaging. Another review article by Enoch (2006) combines environmental and genetic risk factors into models for high risk of alcoholism.Partitioned heritability LDSCHowever, a wide range of analytical tools is available for the study of statistical epistasis in human populations that could be applied to this disease.The shared genetic mechanisms between substance use and mental disorders revealed in this study underscore the importance of thinking about these disorders in tandem,” said NIMH Director Joshua A. Gordon, M.D., Ph.D.This regulation occurs alongside IL4 and interferon alpha, which were commonly upregulated in both AUD and OUD groups.And J.W.S. provided critical support regarding phenotypes and data in individual datasets.In the 170 years since the term “alcoholism” was first classified as a behavior, problematic drinking has been a widely studied condition to settle the nature versus nurture argument.Further, only 5 pathways were exclusively shared between OUD2 and AUD, whereas 9 pathways were shared across AUD, OUD1, and OUD2 (Table S3).Microarray analysis, which allows the simultaneous analysis of up to tens of thousands of genes, now is a routine approach for investigating changes in gene expression on a genome-wide scale and has yielded interesting results in regards to alcoholism.Meanwhile CHRM2 may act through depression and other internalizing symptoms to foster drinking. Family TiesAt coga’s outset, researchers at sites around the country sought to identify families severely affected by alcoholism. Clues in Human VariationsGenes powerfully influence a person’s physiology by giving rise to some 100,000 different types of protein, each of which has a direct role in the daily functioning of the body and brain or in regulating the activity of other genes.Genetics and Alcohol TolerancePathway-level analysis revealed divergent regulation among specific pathways and convergence on others. The Acute Phase Response signaling (APR) and HOTAIR regulatory pathways exhibited co-upregulation in the AUD and OUD1 groups. Pathways exhibiting concordant alterations in both groups present potential therapeutic targets for both disorders. The MDR method is based on the idea that reducing the dimensionality of the data will make the detection of attribute dependencies (e.g., the SNP interactions that determine the classification of case/control) easier for a classifier such as a decision tree or a naïve Bayes learner. The drawbacks to this method include computational time for large datasets or interactions beyond four-way.Biological Epistasis and AlcoholismDSM-V14, 15 on the other hand consolidated AD and abuse as a single disorder as AUD15,16. By considering AD and abuse under single umbrella increased the number of diagnosed subjects, but this number was still not large enough to design powerful GWAS studies. Therefore, many genetic studies of alcoholism also concentrated on nonclinical phenotypes, such as alcohol consumption and Alcohol Use Disorders Identification Test (AUDIT)17–19, from large population based cohorts. The AUDIT, a 10-item, self-reported test was developed by the World Health Organization as a screen for hazardous and harmful drinking and can be used as a total (AUDIT-T), AUDIT-Consumption (AUDIT-C) and AUDIT-Problems (AUDIT-P) sub-scores. This paper reviews the literature on the importance of genetic influences in the development of alcohol abuse and dependence (alcoholism). The alcohol use disorders are fairly typical of most complex genetic conditions in that multiple genetic influences combine together to explain approximately 40% to 60% of the risk.However, one area that requires further methods development is gene–environment interaction.Two genes enriched in the OUD GWAS (LRP8 and PISD), exhibited differential expression in the OUD1 group, while one gene linked to the PAU GWAS, FUT1, showed differential expression in the OUD1 group.We are currently working on how to combine genetic and environmental information to help people understand their level of risk.New genetic variants have been identified, refined endophenotypes have been characterized, and functional information has begun to emerge on known genetic variants that influence risk for and protection from AUD.We used a similar differential expression approach to compare OUD+/AUD+ and OUD+/AUD− groups with the control group. Our ANCOVA analysis identified 30 genes with significant group effects (Fig. S1E; Table S1). Pairwise comparisons revealed that 16 genes were exclusively differentially expressed in the OUD+/AUD− group, while only 3 genes were differentially expressed exclusively in the OUD+/AUD+ group. Two of these genes is alcoholism inherited belonged to the class of lncRNAs, while the other was the protein-coding gene Ethanolamine Kinase 2 (ETNK2) (Fig. S1E).Insight, Not DestinyThe coga project has been structured around families, but this type of research has also strengthened understanding of the relative importance of specific gene variants as risk factors in different ethnic groups. This is not to say that certain ethnicities are more prone to alcoholism; instead, like the ALDH1 gene version that makes many East Asians intolerant of alcohol, certain of the genetic variants that contribute to risk are much more prevalent in some ethnic groups than in others. The knowledge that such genes are likely to be influencing dependence in patients belonging to one of these populations is another tool that can be used to assess the nature of an individual’s problem and to tailor treatment accordingly. As is true of many other human disorders, alcoholism does not have a single cause, nor is its origin entirely genetic. Genes can play an important role, however, by affecting processes in the body and brain that interact with one another and with an individual’s life experiences to produce protection or susceptibility. Teasing these effects apart is challenging, and to date fewer than a dozen genes that influence one’s risk for alcoholism have been identified, although more surely exist.Extended Data Fig. 3 Phenome-wide associations with PAU PRS in PsycheMERGE EUR samples.They also underscore the https://ecosoberhouse.com/ need to understand how subtle differences in physiology can contribute to a disorder as complex as addiction. The brain’s electrical activity patterns, for example, are a form of endophenotype. Using electroencephalography (EEG) to detect such activity through electrodes on the scalp, researchers can record patterns of neural firing. Sophisticated computer algorithms can analyze the data to identify the brain regions where the signals are likely to have originated, offering additional clues to the type of cognitive processing taking place.
