A look at the intersection of genetics and health information in substance abuse
Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle for each person. On January 20, 2015, President Obama announced the Precision Medicine Initiative (PMI) in his State of the Union address. Through advances in research, technology and policies that empower patients, the PMI will enable a new era of medicine in which researchers, providers and patients work together to develop individualized care. Priorities involve the areas where genetic testing is becoming more prolific, specifically in cancer, heart disease and diabetes. However, the number one reason why people go to the doctor in the United States is pain. Genetic Factors in Substance Abuse
Ironically, chronic pain is a more prevalent health condition than cancer, heart disease and diabetes combined and costs the U.S. healthcare system more than all three combined. More than 30% of Americans have some form of acute or chronic pain, and among older adults, the prevalence is over 40%. As rates of chronic pain have dramatically increased over the past 15 years, there has been a similar increase in the prescriptions for pain relievers — specifically opioid pain medications, which are now the most commonly prescribed class of medications in the United States.
In 2014 alone, U.S. retail pharmacies dispensed 245 million prescriptions for opioid pain relievers, primarily for short-term therapy, but 3-4% of the adult population (9.6 million to 11.5 million) were prescribed longer term opioid therapy. When the medications don’t work, or patients are afraid to take the prescription that they filled at the pharmacy, the pills sit on the shelf, or worse, end up in the wrong hands.
It is a personal choice whether someone decides to use alcohol or drugs. It is influenced by multiple biological, familial, psychological and socio-cultural factors. Once a person uses alcohol or drugs, however, the risk of developing alcoholism or drug dependence is greatly influenced by genetics. According to the definition of addiction from the American Society of Addiction Medicine and published research, genes are responsible for about half the risk of alcoholism and addiction, and while genetics are not the sole determinant, their presence or absence may impact the likelihood that a person will become alcohol or drug dependent.
Individual health is a blend of “nature” (or genetics) and “nurture” (or environment). For example, the risk of developing high blood pressure is influenced by both genetics and environment, including diet, stress and exercise. Some diseases, like sickle cell anemia or cystic fibrosis, are caused by a variation in a single gene. However, most diseases, like alcoholism and drug dependence, are considered genetically complex and involve variations in a number of different genes. Individual studies have shown that genetic variations or single nucleotide polymorphisms (SNPs) in dopamine, serotonin, catecholamine, opioid receptors and others are associated with myriad substance use disorders and other aberrant cravings.
Many peer-reviewed published studies demonstrate that substance use disorders run in families. Research conducted on twins and adopted children has shown the impact of genetics in relation to alcohol and drug dependence. In recent years, researchers have identified numerous genes affecting risk for dependence on alcohol and drugs. While no specific “addiction” gene has been identified, a number of different genetic and biological factors make someone more or less vulnerable to becoming an addict.
Due to the evolutionary advantages inherent in preferring foods and chemicals that provide pleasure and benefit, every person has a predisposition for addiction to those things they like. Thus, the potential for addiction is hard-wired into the brain; yet, some people are more predisposed to addiction than others.
In opioid use disorder, this is often seen as a dramatic positive feeling during the first few doses of the medication. It is not observed in patients who are nauseous or dizzy at first. It is that pleasurable feeling that drives further cravings, and the inherent chemical imbalance addressed by the opioid is something that the person has had with them since they were born. As the exposure to the substance increases, the effect weakens and the craving becomes stronger for that initial reaction. Thus, the cravings for consumption increase further and further as time goes on, until what appears to be a quickly fleeting positive feeling turns into a destructive and poisoning addiction.
Repeatedly abusing drugs or alcohol permanently rewires the brain. In fact, studies show that it changes the DNA methylation of a person. If a person starts out with a low genetic predisposition for addiction, he or she can still end up with an addiction based on repeated or excess exposure. If a person repeatedly abuses drugs or alcohol as the result of environmental or other social factors, it can permanently rewire the brain. The more one chases the effect of alcohol and drugs, the greater the chance of developing an addiction.
When combining a complex pathway of genes along with various factors, such as biological and psychological phenotypes, the inherent challenge is to combine this “big data” into something understandable and actionable for the clinician, patient and payer. With the epidemic of substance use order, and specifically, the issues around the prescription opioid and heroin epidemics, the industry is in desperate need of this type of analysis now more than ever.
Today, there are companies who are looking at combining this level of data. Various different genome-wide association studies (GWAS) have looked at genetic predeterminants, and others are looking into data amalgamated from the recent widespread adoption of electronic health records (EHRs) over the past 10 years in order to search for those genetic and clinical factors that affect risk for substance use disorder. Through the integration of these datasets, researchers should be able to construct viable hypotheses to support predictive models for risk of alcoholism, drug dependence and opioid abuse. By synthesizing clinical and genetic data in substance abuse, precision medicine offers the potential to combine “nature” and “nurture” into a complete picture which may help spare individuals, families and neighborhoods the incredible difficulties and costs associated with the disease of addiction.