By Daniel T. Brown DO ABPM-ADM, Regional Medical Director in Ohio and Pennsylvania, Pinnacle Treatment Centers
In 1953, scientists accurately described the structure of DNA for the first time.
That was revolutionary.
As we know now, DNA – short for deoxyribonucleic acid – exists in every form of organic life on earth. DNA contains sequences of nucleic acids that – when combined in specific patterns and activated by helping molecules like mRNA (messenger RNA) and tRNA (transfer RNA) – tell the machinery of a cell how to build proteins that then carry out the basic molecular functions essential for life.
Every living cell on earth contains DNA – and we know how it works.
That’s truly amazing.
In 1990, scientists embarked on ambitious project. They began mapping the entire human genome. Called The Human Genome Project, the National Institutes of Health (NIH) completed their work in just under thirteen years. This was a truly remarkable feat. It’s had a significant impact on the study of human biology in general. It helps medicine in particular. We’ll let the leaders of the project describe the accomplishment in their own words:
“The Human Genome Project is one of the greatest scientific feats in history. The project was a voyage of biological discovery led by an international group of researchers looking to comprehensively study all of the DNA (known as a genome) of a select set of organisms. Launched in October 1990 and completed in April 2003, the Human Genome Project’s signature accomplishment – generating the first sequence of the human genome – provided fundamental information about the human blueprint, which has since accelerated the study of human biology and improved the practice of medicine.”
To create the genome map, scientists collected thousands of samples of DNA to create a genome reference bank. That bank now contains hundreds of thousands of DNA samples. It allows scientists to conduct a new kind of study, called a Genome-Wide Association Study, or GWAS.
Genome-Wide Association Studies, Alcohol Use Disorder, and Problem Drinking
A GWAS allows researchers to compare genes of individuals with certain medical disorders or conditions against genes of individuals without those disorders or conditions. This allows researchers to learn which genes may or may not contribute to those disorders or conditions.
To date, scientists have identified genes directly related to:
- Prostate cancer
- Obesity
- Type 2 diabetes
- Parkinson’s disease
- Various cardiac disorders
In recent years – as the genome bank collects more and more data – researchers turned their attention to using the GWAS approach to identify genes related another type of chronic medical condition: the disordered use of substances such as drugs and alcohol. The holy grail of this research is to identify one gene – or one set of genes – related to addiction. That’s what they call a marker. A marker is a gene or set of genes that indicate whether an individual has increased likelihood of develop an alcohol or substance use disorder, compared to a person without the marker.
This article will review what we know about the relationship between genes, heavy drinking, and alcohol use disorder. We’ll pay special attention to recent research conducted at Center for Studies of Addiction at the Perelman School of Medicine in Pennsylvania.
We’ll start with data from the first large-scale GWAS on alcohol and substance use disorder, conducted in Sweden in 2014. Results from that study showed:
- In males, heritability of substance use disorder was 55%
- In females, the heritability of substance use disorder was 73%
Here’s what heritability means.
“The extent to which genetic individual differences contribute to individual differences in observed behavior.”
This study classified alcohol as a substance. Therefore, what these results mean – or meant, as of 2014 – was that in men, almost half of an individual’s behavior related to alcohol consumption can be explained by the presence of specific genes. In women, almost three-quarters of behavior related to alcohol consumption can be explained by the presence of specific genes.
Now let’s take a look at the latest information on genetics and alcohol use disorder from the Perelman School of Medicine in Pennsylvania.
Problem Drinking, Alcohol Use Disorder, and Genetic Heritability
The Center for Studies of Addiction at the Perelman School has published several studies on the relationship between genes and alcohol use disorder. In 2019, they released the largest study conducted in the U.S. on the genetics of alcohol use. The sample set of 275,000 individuals was not as large as the study conducted in Sweden, though. That study included data on over one million individuals. This GWAS was large enough for us to make population-level generalizations from the results.
Here’s what the researchers found in that GWAS on alcohol use.
- Problem Drinking. Results indicated 13 genes and derivatives directly related to problem drinking.
- Alcohol Use Disorder. Results indicated 10 genes and derivatives directly related to alcohol use disorder.
- Problem Drinking and AUD. Results indicated 6 genes and derivatives directly related to heavy drinking and AUD.
In this context, problem drinking refers to heavy drinking, defined as consuming more than 4 drinks a day or 14 drinks a week for men, and 3 drinks a day or 7 drinks per week for women, while alcohol use disorder refers to drinking that meets the clinical criteria for AUD defined by the Diagnostic and Statistical Manual of Mental Disorders, Volume 5 (DSM-V) and explained thoroughly in this article in the blog section of our website:
Defining Alcohol Use Disorder
Another study conducted in the United Kingdom, which we discuss in our article Research Report: The Effect of Alcohol on Aging, found that drinking moderate amounts of alcohol had an adverse impact on a structural component of our DNA called telomeres.
That study showed the following:
- People who consumed alcohol in amounts considered heavy had increased risk of damage to telomeres than non-drinkers or moderate drinkers
- People who met the clinical criteria for AUD has increased risk of telomere damage compared to non-drinkers, mild drinkers, and moderate drinkers
Which bring us to the current study. Telomere length is an indicator of aging. Generally speaking, the older you get, the shorter your telomeres get. That’s why researchers now say alcohol consumption – at mild or moderate levels – accelerates the aging process. The new study offers data on a new metric related to the brain and aging. It measured the relative amount of white and gray matter present in the brain of an adult human.
Daily Drinking, Shrinking Brain, and Cognitive Decline
Dr. Henry R. Kranzler, director of the Center for Studies of Addiction at the University of Pennsylvania, the research center mentioned above, works every day to learn more about the genetic component of alcohol and substance use disorders. For the past twenty years, he’s explored the potential of gene therapy – a.k.a. medications designed to act on targeted genetic sequences – to help either prevent alcohol and substance use disorder or support people in recovery from alcohol or substance use disorder.
Here’s how he described his research in a recent interview published in the print and online news resource, The Philadelphia Inquirer:
“Theoretically, if you genotype a large sample of people with alcohol use disorder you can use the information to calculate a single risk score, which could be used to determine who is going to benefit from a specific type of medication to treat the disorder.”
The challenge with alcohol use disorder is that there are multiple genes involved, each of which has a unique contribution to the overall disorder. That means AUD is polygenic. Other poygenic traits – like height, for instance – involve over 11,000 genes. While it’s not impossible to identify the specific risk and protective variants in each gene group for each trait – like alcohol use disorder or height – that’s what makes the next step in this research complex. Developing a polygenic risk score has worked for some disorders, but scientists do not have enough information to develop “individual for psychiatric disorders for use in a prevention or treatment context,” according to Dr. Kranzler.
His latest research, however, has identified something important: consuming more than one standard alcoholic beverage per day – think one regular twelve-ounce bottle of beer or one regular eight-to-twelve-ounce glass of wine – has a negative impact on the human brain. This finding was part of the study on telomere length, but focused on changes in the volume of gray and white matter in the brain, as opposed to telomere length.
The Results: Brain Volume and Alcohol Consumption
First, let’s talk about gray and white matter.
Brain cells are both gray and white, with the gray and white colors corresponding to different sections of the cells themselves. Most brain cells have two parts: a body and a connecting structure. The bodies of our brain cells are gray. These are neurons. They make up what’s called our gray matter. The structures that connect brain cells are white. These are axons. They make up what’s called our white matter. White and gray matter are part of the same system, with different functions, and work together for optimal brain function. Gray matter is where our brains process information – i.e. thinking, feeling, and deciding – and white matter is how our brains communicate the information that’s processed.
Now let’s look at what Dr. Kranzler and his colleagues found.
Alcohol and the Brain: When Problems Can Start
- Consuming more than one alcoholic beverage per day was associated with lower gray matter volume, compared to drinking one or fewer alcoholic beverages per day
- Consuming more than one alcoholic beverage per day was associated with lower white matter volume, compared to drinking one or fewer alcoholic beverages per day
- The physical characteristics of white matter – meaning its organization and structural integrity – deteriorated with levels of alcohol consumption exceeding one drink per day
You can see why a reduction in both white and gray matter concerns researchers: both play a role in how our brain functions and communicates. Decreased processing power and impaired ability to communicate, combined, have a negative impact on how our brain works, which, ultimately, means a decrease in overall cognitive function.
The fact that consuming more than one alcoholic beverage per day, but less than what federal guidelines indicate is risky, means that right now, many people in the U.S. drink more than is healthy without realizing it. The current guidelines for drinking tell us that for women, about 7 drinks a week is safe, but for men, about 14 drinks a week is safe.
But are those levels of consumption really safe?
How We Can Use This Information
Dr. Kranzler thinks we need to adjust those guidelines to bring them into alignment with the latest research on the negative impact of alcohol on both telomere length and white/gray matter volume. Specifically, he thinks the current guidelines are “…too much for men, but probably about right for women.”
This brings us to a unique place in our understanding of alcohol use disorder. Evidence shows two sets of facts that appear to conflict.
- Alcohol consumption guidelines tell us that for males, about 14 drinks a week does not increase risk of developing alcohol use disorder.
- Experimental data tells us that consumption of more than one drink per day – or more than 7 drinks per week – can lead to reductions in telomere length, gray matter, and white matter.
Telomere length impacts aging, while gray and white matter directly impact typical cognitive function. Therefore – excluding women, for the moment – consuming alcohol at levels considered safe may have a negative impact on cognitive function in men.
That’s a conundrum.
But it’s a conundrum we can resolve in one simple way. We can reduce our alcohol consumption. We can reduce it to about one drink per day. That’s no more than 7 drinks per week. The latest evidence indicates that consuming alcohol at that level does not impact telomere length or white and gray matter volume. Therefore, it should not have a negative impact on overall cognitive function.
That’s how we can all play it safe with alcohol.
One more thing. if you’ve ever considered quitting drinking, or regularly consume more than one drink per day, or more than seven drinks per week, we encourage you to visit our page on alcohol use disorder. Please read the information we provide. You’ll learn more about treatment and support disordered or problem drinking.