{"id":428166,"date":"2025-09-16T06:06:25","date_gmt":"2025-09-16T06:06:25","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/428166\/"},"modified":"2025-09-16T06:06:25","modified_gmt":"2025-09-16T06:06:25","slug":"what-do-we-really-know-about-genetics-and-alcohol-use-disorder","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/428166\/","title":{"rendered":"What Do We Really Know About Genetics and Alcohol Use Disorder?"},"content":{"rendered":"

Why are some people able to give up alcohol with ease, while others struggle for years? That\u2019s the question driving the work of biostatistician Laura Saba<\/a>, PhD.<\/p>\n

Saba is an associate professor of bioinformatics at the Skaggs School of Pharmacy and Pharmaceutical Sciences<\/a> at CU Anschutz. Her lab investigates the biological mechanisms underlying diseases such as alcohol use disorder (AUD) to inform drug development, while also working to identify individuals who may benefit from specific treatments based on their genetics.<\/p>\n

\u201cAlcohol use disorder is a heterogeneous disease, and we still don\u2019t fully understand all the pathways involved,\u201d Saba said. \u201cWe don\u2019t even know exactly which brain regions or cell types are most important.\u201d<\/p>\n

AUD is estimated to be about 50% heritable, meaning genetic factors play a role in developing the disease. This estimate comes from studies on twins separated by adoption and is verified by animal studies, Saba said.<\/p>\n

As a biostatistician, Saba uses mathematical models that could lead to pharmaceutical interventions for people with AUD.<\/p>\n

\u201cI\u2019m working to mathematically describe the \u2018nature\u2019 part \u2013 specifically, the biological link between a genetic difference and the alcohol-related phenotype we observe in the lab,\u201d she said. \u201cAlcohol use disorder is not a \u2018pull yourself up by the bootstraps\u2019 type of illness, which is hard for people to understand and accept. I hope our work can help people better understand how this disease causes real and incredibly complicated physical changes in the brain.\u00a0<\/p>\n

\n

This article is part of a CU Anschutz Newsroom series exploring addiction, a serious public health issue our doctors and researchers are working hard to address.\u00a0<\/p>\n

See other articles in the series<\/a>.<\/p>\n<\/blockquote>\n

Examining the genetics of \u2018tolerance\u2019<\/p>\n

In the 1990s, a groundbreaking study by Marc A. Schuckit, MD, linked genetics to AUD. He followed a group of sons of individuals with AUD, beginning in childhood and tracking them over 30 years to see who developed the disorder and who did not.<\/p>\n

An anecdote from his early work stuck out to Saba and other researchers.<\/p>\n

\u201cWhen interviewing people with alcohol use disorder, many would say things like, \u2018For years, I was the person who could drink 12 beers and still drive home. Alcohol didn\u2019t affect me. I had a really high tolerance,\u2019\u201d she said.<\/p>\n

People who don\u2019t immediately feel the rewarding effects of alcohol tend to drink more, Saba said.<\/p>\n

\u201cAlcohol is a toxin, so even for people who don\u2019t feel the effects, it\u2019s still affecting their brain,\u201d she said.<\/p>\n

The study found that people with a high tolerance are more likely to suffer negative consequences through continued use, pulling them deeper into the addiction cycle. Once people fall into the addiction cycle, they have less control of their drinking and find it hard to stop, even if it\u2019s hurting them.<\/p>\n

The groundbreaking nature of Schuckit\u2019s study led Saba to begin studying tolerance and other traits related to AUD in 2005, collaborating with Boris Tabakoff<\/a>, PhD, professor at the Institute for Behavioral Genetics<\/a> at CU Boulder<\/a> and Paula Hoffman<\/a>, PhD, professor emerita at CU Anschutz School of Medicine<\/a>.<\/p>\n

Isolating traits of alcohol use in the lab<\/p>\n

To better understand the role genes play in AUD presentations, Saba and her colleagues used animal models to break down measurable behaviors. They isolated behaviors and measured degrees of consciousness, motor coordination and other behavioral patterns associated with alcohol self-administration.<\/p>\n

Early paradigms looked at choice, giving the mice an option to choose between water and alcohol. Even in passive studies, Saba noted that while they didn\u2019t often drink to intoxication, they did choose to drink alcohol. This helped her team investigate why one animal drinks more than another.<\/p>\n

\u201cAs a statistician, this lets me track the full sequence of behaviors, measure brain traits, and compare animals with and without alcohol exposure to see where differences emerge,\u201d Saba said.<\/p>\n

It\u2019s ongoing work. Because there\u2019s no single \u201calcohol use disorder gene,\u201d it\u2019s allowing her to look at genetic differences that can disrupt the brain and increase susceptibility.<\/p>\n

\n

Does immunity play a role in alcohol use disorder?<\/p>\n

\u00a0<\/p>\n

Tabakoff and colleagues were one of the first to propose a role for immunity in the brain related to alcohol susceptibility. It\u2019s an idea that Saba says is showing up in human studies as well.<\/p>\n

\u00a0<\/p>\n

\u201cIn the last 10 years, we\u2019re starting to gather evidence of the way your brain\u2019s immune system reacts to external stimuli \u2013 how it responds to what it sees as \u2018invaders\u2019 \u2013 and how this might play a key role in how susceptible someone is to alcohol use disorder,\u201d Saba said.<\/p>\n<\/blockquote>\n

Heritability doesn\u2019t mean AUD is destined<\/p>\n

Unlike some genetic diseases \u2013 such as the connection between BRCA1 and BRCA2 gene mutations and breast cancer \u2013 alcohol use disorder depends heavily on environment and behavior.<\/p>\n

\u201cWe have to be careful when we talk about \u2018predisposition,\u2019 genetically-speaking. It doesn\u2019t mean someone is destined to develop alcohol use disorder, because you still have to drink for that to happen,\u201d Saba said.<\/p>\n

Her work isn\u2019t about predicting who will drink and who won\u2019t. Instead, her team focuses on understanding networks in the brain to understand why some animals are resistant.<\/p>\n

Finding needles in a genomic haystack<\/p>\n

Saba and colleagues aim to identify the networks associated with resistance to AUD in the mice and rats they\u2019ve studied using big data and omics approaches. They were able to identify a network associated with alcohol consumption in the two-bottle choice test, which identified some animals that loved alcohol and others that wouldn\u2019t touch it.<\/p>\n

They identified a gene in the middle of a network that wasn\u2019t included in a gene annotation database.<\/p>\n

\u201cThe gene didn\u2019t have a name, and we didn\u2019t know what it did, or even if the gene made a protein or acted as a regulator,\u201d she said. Working with another group, they used CRISPR-Cas9 \u2013 a gene editing tool \u2013 to remove the gene in the animal models to observe the behavior.<\/p>\n

Rats without this unnamed gene drank more alcohol than those with it.<\/p>\n

They also looked at how other genes changed as the result of the removal of this gene.<\/p>\n

\u201cWe found evidence that this gene regulates how RNA is processed in cells, and this is helping us to better understand its role,\u201d Saba said.<\/p>\n

Why lab work is important to understand AUD<\/p>\n

It\u2019s enormous work to identify the myriad ways genes express. Saba and her colleagues continue to comb the data from the animal-based alcohol studies, contributing to the body of work happening worldwide to unravel the mysteries of AUD.<\/p>\n

\u201cThe nature of alcohol use disorder is truly devastating \u2013 not just for the person who has it, but for their loved ones as well,\u201d she said. \u201cUltimately, I hope the work we\u2019re doing will go toward raising awareness and improving intervention.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"Why are some people able to give up alcohol with ease, while others struggle for years? That\u2019s the…\n","protected":false},"author":2,"featured_media":427329,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[267,70,16,15],"class_list":{"0":"post-428166","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-genetics","9":"tag-science","10":"tag-uk","11":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/115212477019576217","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/428166","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=428166"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/428166\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/427329"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=428166"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=428166"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=428166"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}