Furthermore, the best-powered GWAS of SUDs to date have been conducted primarily in samples of European ancestries, limiting their predictive utility to individuals who are also of European ancestry (Martin, Daly, Robinson, Hyman, & Neale, 2019). Finally, PGS can be difficult to interpret in layperson’s terms (i.e. being in the 95th percentile of polygenic risk for alcohol dependence does not mean you have a 95% chance of developing the disorder). Further research is needed to fully understand the potential benefits, and possible harms, of incorporating genetic information (e.g. PGS) into SUD treatment planning (Driver, Kuo, & Dick, 2020; Lebowitz, 2019; Lebowitz & Ahn, 2018). Although researchers found environmental factors played a larger role, opioid polygenic risk scores explained 8% of the variance of the risk for opioid dependence. The study also found that among people with higher polygenic risk scores, individuals with a higher education level were less likely to have opioid dependence, whereas those with posttraumatic stress disorder (PTSD) were more likely to have opioid dependence.

1. It was supported by the National Institute on Drug Abuse (NIDA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Mental Health (NIMH), the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute on Aging.
2. NIDA and other Institutes at NIH supported a recently released report on responsible use and interpretation of population-level genomic data, by the National Academies of Sciences, Engineering, and Medicine.
3. Even if you have a genetic predisposition to addiction, you can take steps to manage your risk and minimize your chances of addiction.
4. Opioid neurotransmission is also crucial for signaling in the brain’s reward pathway and, while directly relevant to heroin addiction, this neurotransmission pathway also modulates the acute and chronic responses to other substances of abuse (e.g., alcohol, nicotine, cocaine, and others).
5. (2012, this issue) contribution discusses the role of genes involved in GABA in alcoholism and nicotine addiction.

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Substance-specific genes include genes for metabolic enzymes (ALDH2, ADH1B) as well as genes encoding gatekeeper molecules such as drug receptors (eg, nicotinic receptors, OPRM1). SUD afflicted individuals frequently present with a comorbid condition, either a co-occurring addiction to a different drug or another psychiatric disorder. This clinical reality points to the existence of common genetic factors underlying vulnerability to both comorbid conditions. The paper in this issue by de Leon and Diaz (2012) discusses how comorbid conditions can be harnessed to investigate the genetics of SUD (in this case the comorbidity of schizophrenia or mood disorders with nicotine addiction). Although nicotine addiction and schizophrenia demonstrate the highest comorbidity rates, other diseases, and particularly mood disorders, also exhibit very high prevalence rates of smoking. The letter to the editor by Lawrence et al. (2012) in this issue provides evidence that the comorbidity between nicotine addiction and depression is not driven only by depressed patients’ higher rates of abusing other drugs concomitantly to nicotine, but also by the direct effects of nicotine itself.

In their paper in this issue, Levran et al. (2012) review the various genes implicated in opioid neurotransmission and their associations with SUD, including the response to therapeutic interventions in the treatment of alcoholism and heroin addiction. Heritability estimates from twin studies of CanUD range from ~0.51 to 0.59, slightly higher than the estimates for cannabis use/initiation (~0.40–0.48; Agrawal & Lynskey, 2006; Verweij et al., 2010). Twin and family studies have found shared genetic and environmental influences across the stages of cannabis use and abuse (Agrawal, Neale, Jacobson, Prescott, & Kendler, 2005; Van den Bree, Johnson, Neale, & Pickens, 1998). Rare genetic variants relevant to addiction have been found within the serotonin receptor 2B gene (HTR2B) and MAOA, and several of the functional CYP26 alleles are also rare or uncommon. Both HTR2B and MAOA influence impulsivity and behavioral control and findings for these genes in humans remarkably parallel animal models.

A recent exome-chip meta-analysis of 16 studies fine-mapped 124 GWS rare coding variant associations across nicotine use outcomes i.e. CPD, pack-years (i.e. quantity of cigarette packs smoked in lifetime), smoking initiation, age of smoking initiation; Brazel et al., 2019. Rare variation accounted for 1.0–2.2% of phenotypic variance across these traits (Brazel et al., 2019). Twin studies can to some extent disentangle the roles of genetic heterogeneity and polygenicity–epistasis. 2,14 under the epistatic model, combinations of genetic variants, each represented as a puzzle piece, determine phenotypes.

The findings in one study showed that environmental factors explained more of the risk for opioid dependence than polygenic risk scores—a number estimating how genetic variants affect an individual’s risk of developing a disease. The researchers found selected environmental factors, such as annual household income and education level, explained an average three-fold greater risk for opioid use disorder (OUD) compared with opioid use disorder polygenic risk scores alone. Substance use disorders (SUDs) are heritable psychiatric disorders Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5); American Psychiatric Association, 2013 that are influenced by both environmental and genetic factors. Given the public health burden of SUDs, a better understanding of SUD etiology is of wide-reaching importance. Genetic studies have begun to elucidate the molecular mechanisms underlying SUDs and related traits, including other psychiatric conditions with which SUDs frequently co-occur (Grant et al., 2016; Kessler, 2004).

Opioid Use Disorder

But does that mean your chance of addiction is essentially a coin flip if you have a family history of SUD? 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. It was supported by the National Institute on Drug Abuse (NIDA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Mental Health (NIMH), the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute on Aging. It’s increasingly common for someone to be diagnosed with a condition such as ADHD or autism as an adult. It is also known that pain, either psychological or physical, as well as PTSD and trauma, can make AUD more likely, as the additive relief of distress seems to increase brain-related rewards derived from alcohol. Details about upcoming events—including meetings, conferences, workshops, lectures, webinars, and chats—sponsored by NIMH.

AUD Protections and Risks

The paper in this issue by Tsuang et al. (2012) discusses the complex interactions that underlie the comorbidity between nicotine addiction and depression, which are confounded by the antidepressant effects of smoking (both through nicotine and through inhibition of MAO A by cigarette smoke). They also discuss the potential causality role that early exposure sobriety gift ideas for him to nicotine may have in increasing the risk of depression. Four articles in this Special Issue discuss and review the value of animal models to study the contribution of genetic variation to SUD risk.

Alcohol use disorder (AUD) has been studied for years, starting with twin studies comparing identical or fraternal twins and their risk for AUD and adoption studies comparing adopted children to their birth parents. Some genes increase a person’s risk for AUD, while others decrease that risk directly what happens if i report a drug dealer to the police or indirectly. For instance, some people of Asian descent carry a gene variant altering their rate of alcohol metabolism, causing symptoms like flushing, nausea, and rapid heartbeat when they drink even a little alcohol. “Substance use disorders and mental disorders often co-occur, and we know that the most effective treatments help people address both issues at the same time.

Forty years maverick sober living later, and thanks to the findings from epidemiology and genetics studies, the general concept that addiction “runs in families” is beyond dispute, but teasing apart the timing, strength and contingent nature of the genetic contribution to addiction remains the focus of challenging research. As a result of Anton’s research, it’s clear that personalized treatment and choosing the right medication for the right patient is becoming possible in AUD. For example, performing a few relatively simple genetic tests identifying variations in three brain genes will enable physicians to predict which patients would benefit most from taking naltrexone, an FDA-approved medication for AUD. Rather than taking a drug that could never work well because of one’s genetic makeup, wouldn’t it be best to know this upfront and potentially choose an alternative?