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Accumulation of acetaldehyde is responsible for the physiological malaise commonly known as ‘hangover’. Alcohol tolerance occurs when you use alcohol in the same amounts over time and no longer get the same effects, so you need to increase the amount. Alcohol use disorder (AUD) is a leading cause of death and disability worldwide and is characterized by frequent and problematic drinking behaviors, such as binge drinking, loss of control, and continued drinking despite harmful consequences. 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. She said their study opens numerous doors for future research, chasing down possible connections between the alcohol-protective alleles and conditions that have no apparent connection with alcohol consumption.
Sanchez-Roige and Palmer noted that their group has developed a 10-year partnership with 23andMe that has focused on numerous traits, especially those with relevance for addiction. Published today in Nature Mental Health, the study was led by researchers at the Washington University in St. Louis, along with more than 150 coauthors from around the world. B, Ninety-two regions in a cross-ancestry analysis were fine mapped and a direct comparison was done for these regions in EUR. C, Comparison for the highest PIPs from cross-ancestry and EUR-only fine mapping in the 92 regions. Red dots are the regions fine mapped across EUR, AFR and LA; blue dots are the regions fine mapped across EUR and AFR; green dots are the regions fine mapped across EUR and LA; and black dots are the regions only fine mapped in EUR.
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Extended Data Fig. 1 Manhattan and QQ plots for PAU/AUD meta-analyses in different ancestries.
This has resulted in a paradigm shift away from gene centric studies towards analyses of gene interactions and gene networks within biologically relevant pathways. Research suggests that genes can influence a person’s risk of developing an addiction to alcohol. Certain genetic variations can make individuals more susceptible to developing alcohol dependence. Overall, genetics play a significant role in the co-occurrence of alcohol addiction and mental health disorders.
In retrospect, those studies (despite sample sizes in the range of 1000–2000) were largely underpowered to detect risk variants of small effect. Current power and sample size estimates for GWAS with effect sizes of 1.05–1.2 range from 30,000 – 120,000 (Owen et al., 2010; Schizophrenia Working Group of the Psychiatric Genomics, 2014). While the use of a stringent P-value for GWAS avoids the detection of false positive findings, it might also miss ‘true’ variants. Recent attempts to address this issue have used pathway analysis and polygenic risk score approaches (Gelernter et al., 2014) but have not been widely applied to AUD genetic analyses. For the study, the researchers used genetic data from the multi-ethnic Million Veteran Program (MVP), a national, voluntary research program sponsored by the Department of Veterans Affairs, which includes white, African-American, Latino, and Asian participants.
- By further studying the genetic factors involved, we can better understand alcoholism and develop more effective strategies to prevent, diagnose, and treat this serious condition.
- However, sex-stratified GWAS also identified two female-specific signals for AUDIT-C (Supplementary Data 3, Supplementary Figs. 9, 10) and one for AUD (Supplementary Data 4, Supplementary Figs. 11, 12).
- By modifying these genes, scientists aim to enhance an individual’s ability to break down and eliminate alcohol from their system.
Supplementary Data 41
Understanding the genetic influences on alcoholism in different populations is crucial for developing personalized treatment approaches. Genetic testing can help identify individuals who are at a higher risk and tailor interventions accordingly. By targeting specific genetic factors and considering the environmental context, healthcare professionals can optimize treatment outcomes and provide effective support to individuals struggling with alcohol addiction. Certain gene variations can increase the risk of developing alcoholism, while others may decrease the risk. These genetic variations can affect the way our bodies metabolize alcohol, alter brain chemistry, and influence behavior.
Further research is needed to explore the precise mechanisms through which ALDH gene variants influence alcohol metabolism and addiction risk. By understanding the genetic factors involved in alcoholism, scientists hope to develop more effective prevention strategies and treatment options for individuals affected by this complex disease. Although the serotonin transporter gene is not the sole determinant of alcoholism, it does contribute to an individual’s genetic predisposition to the disease. Inheritance of this variant can increase the likelihood of developing alcoholism, especially in individuals who are exposed to environmental risk factors such as early exposure to alcohol or a family history of alcoholism. COGA ascertained probands in treatment for alcohol dependence, and a smaller number of comparison individuals from the same communities, and then recruited their families.
However the use of microarrays and advances in next-generation RNA-sequencing (RNA-Seq) 35 have conferred the ability to quantify mRNA transcripts in postmortem brain and analyze expression differences between alcoholics and controls within gene networks 36–39. Epigenetic modifications, such as DNA methylation and histone modifications, play a crucial role in gene regulation and have been implicated in addiction-related behaviors. Future research should investigate how epigenetic changes contribute to alcohol addiction and whether these modifications can be targeted for therapeutic purposes. Furthermore, targeting specific behaviors and risk factors can also be effective in preventing addiction. This can include implementing policies to reduce access to alcohol, implementing early intervention programs for at-risk individuals, and promoting healthy coping mechanisms for stress and emotional challenges. Currently, treatment for alcoholism typically includes a combination of therapy, support groups, and medication.
Other Genetic Factors For Developing AUD
Similarly, individuals with genetic variations in the brain’s reward system may benefit from targeted therapies that modulate dopamine release, helping to reduce cravings and prevent relapse. It is important to note that genetic testing for alcoholism predisposition does not guarantee that an individual will develop the disease. Environmental factors, such as exposure to alcohol and lifestyle choices, also play a significant role in the development of alcoholism. While genes play a significant role in predisposing individuals to alcoholism, environmental factors also have a notable impact.
Overall, family history is an important factor to consider when assessing an individual’s risk for alcohol addiction. While genetics can contribute to an increased susceptibility, it is important to recognize the role of environment and individual choices in the development of alcoholism. By evaluating these factors, healthcare professionals can develop personalized treatment plans and interventions to support individuals at risk and help drug addiction them overcome alcohol addiction. Understanding the genetic factors that increase the risk of alcohol addiction can have important implications for the treatment and prevention of this disorder. By identifying individuals who may be at a higher risk, healthcare professionals can provide targeted interventions and support to help reduce the likelihood of developing alcohol addiction.
For AUD, we identify 23 GWS genes in EAs, 5 in AAs, and 1 in LAs (Supplementary Fig. 14), many of which are GWS loci in the SNP-based analyses for that trait. For AUD, the loci in EAs that are not GWS in the SNP-based analyses are KRTCAP3, TRMT10A, ZNF512, DCLK2, MTTP, and MCC. The risks of smoking were first widely publicized by the Surgeon General’s Report of 1964, and the combination of that medical information and social pressure has reduced the prevalence of smoking over the subsequent decades. An individual’s awareness of personal genetic medical risks may similarly change his or her choices. The broader health and social effects of this new type of information may not be seen quickly, but they could be quite profound over time.
PRS for phenome-wide associations
Thus, when investigating the biology of alcoholism, researchers must carefully define the problem–for example, distinguishing between true dependence on alcohol and alcohol abuse, which is a less medically severe syndrome. The goals of this renewal concept are to continue to integrate and share COGA data and to continue to add data across the lifecycle, specifically in drug addiction the adolescent and young adult (Prospective Study) and older adult (Lifespan Study) cohorts. GCTA/GREML, or GCTA, is a statistical method which estimates variance in genetics by quantifying the chance genetic similarity of individuals and comparing their similarity in trait measurements. By quantifying the additive contributions of a subset of genetic variants (SNPs) to a trait’s heritability, GCTA can corroborate the findings of GWAS studies. If the GCTA estimate of SNP heritability is consistent with the total genetic heritability, it is implicated that those genetics variants have a causal effect on the observed phenotype (Yang et al., 2011). AUD is a complex disorder, and likely hundreds if not thousands of genes contribute to its broad and varied phenotype.
The researchers analyzed genetic data from the 3 million 23andMe research participants, focusing on three specific little snippets of DNA known as single-nucleotide polymorphisms, or SNPs. Sanchez-Roige explained that variants, or alleles, of these particular SNPs are “protective” against a variety of alcohol behaviors, from excessive alcohol drinking to alcohol use disorder. Given the challenges faced by individuals with a genetic predisposition to alcoholism, it is crucial to have supportive networks in place to assist and guide them through their journey towards recovery. These networks can provide the necessary resources, information, and emotional support to help these individuals navigate the complexities of their condition.
They can be a place for individuals to discuss their struggles, seek advice, and learn from others who have successfully managed their genetic predisposition to alcoholism. This sense of community can help combat feelings of isolation and provide a strong support system for individuals on their journey to recovery. One of the areas of focus in pharmacogenetics is determining an individual’s response to medications that aid in the prevention of relapse. Certain medications, such as naltrexone and acamprosate, are commonly used to reduce cravings and maintain sobriety.
