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Can Our Genes Really Predict Our Disease Risk?

Naouras Bouajila

French Society of Alcoholology and Addictology (SF2A)

Introduction

Alcohol remains one of the leading preventable risk factors worldwide. It is implicated in a wide range of chronic conditions, including cancers, cardiovascular and liver diseases, as well as neurological disorders such as dementia. Each year, alcohol use accounts for hundreds of thousands of deaths, and recent data from the Global Burden of Disease Study highlight that alcohol-related disorders rank among the top global causes of years lived with disability.

In response to this evidence, several countries have revised their drinking guidelines, with some going so far as to state that there may be no truly “safe” level of alcohol consumption. Yet, the debate is far from settled. A number of observational studies have suggested that light or moderate drinking might exert protective effects, particularly against certain cardiovascular diseases. But how reliable are these findings?

The AlcoolConsoScience Project: Better Information for Better Prevention

The AlcoolConsoScience project, to which our study directly contributes, was established to strengthen the scientific foundations of public health communication on alcohol. Its primary objectives are to provide rigorous scientific syntheses through systematic reviews, to develop tailored communication tools for healthcare professionals and patients, and to create a dedicated website that challenges misconceptions while disseminating reliable information on alcohol and its health effects (https://sfalcoologie.fr/acs-alcool-conso-science/) .

The project is coordinated by the French Society of Alcoholology and Addictology (SF2A) and is funded by the “Fonds de lutte contre les addictions”, with support from the “Assurance Maladie” and the French Interministerial Mission for Combating Drugs and Addictive Behaviours (MILDECA) .

Beyond producing scientific and educational resources—including literature reviews, original studies, posters, videos, podcasts, and training materials—the project relies on specialized working groups that bring together researchers, clinicians, and experts. These groups address key topics such as alcohol and cancer, alcohol and psychiatric or dual disorders, alcohol and women, alcohol and social vulnerability, alcohol and interactions with medications, as well as the combined effects of alcohol and tobacco on health outcomes.

All of these resources are consolidated on a single online platform, designed to serve as a reference for both healthcare professionals and the general public, with the overarching goal of improving knowledge, strengthening prevention, and supporting better care.

Our systematic review of Mendelian randomization studies is part of this initiative, contributing new scientific insights to guide public health messaging and evidence-based practice.

Mendelian Randomization: A “Natural Experiment”

In epidemiology, a central objective is to examine the relationship between an exposure—such as alcohol consumption—and the development of chronic disease. To address this, researchers rely on various methodological approaches. Randomized controlled trials (RCTs) are considered the gold standard, as the random allocation of treatment to participants minimizes confounding and enables robust causal inference. However, RCTs cannot be applied to all exposures, particularly harmful substances like alcohol or tobacco, where it would be unethical to deliberately assign consumption. Consequently, observational studies are often used, providing valuable insights from real-world data, but their findings remain vulnerable to residual biases. Confounding is the most common limitation: for example, when studying the association between smoking and esophageal cancer, alcohol acts as a confounder since it is correlated both with smoking and with cancer risk, complicating causal interpretation.

To overcome these challenges, an intermediate methodological approach has emerged over the past two decades: Mendelian Randomization (MR). This method exploits the random allocation of genetic variants inherited from parents at conception, a process that mirrors randomization in clinical trials. Specific genetic variants can thus serve as instruments to study the causal effects of modifiable exposures. In the context of alcohol, a well-known example is the ALDH2 gene variant, which induces alcohol intolerance (flushing, palpitations). Individuals carrying this variant typically consume substantially less alcohol; by comparing their health outcomes with those of non-carriers, researchers can estimate the causal role of alcohol consumption, independent of lifestyle or environmental confounders such as smoking or diet.

Mendelian Randomization offers several advantages. Because genetic variants are randomly assigned at conception, the approach reduces confounding from socioeconomic or behavioral factors and helps clarify controversial findings from observational studies. Yet limitations remain: the genetic variants used must be strongly and specifically associated with the exposure of interest, and must not influence the outcome through alternative biological pathways (pleiotropy). Moreover, the observed effects are often modest, requiring very large genetic datasets to achieve adequate statistical power.

Ultimately, Mendelian Randomization occupies a position at the interface between randomized trials and observational research. It is a powerful methodological tool that strengthens causal inference in public health. Within the framework of our systematic review, it provides critical insights into the true effects of alcohol consumption on health, while addressing the methodological limitations inherent in traditional epidemiological approaches.

What Did Our Systematic Review Reveal?

In our systematic review, we analyzed 70 Mendelian Randomization (MR) studies that explored the causal role of alcohol consumption in four major disease groups: cancers (26 studies), cardiovascular diseases (24 studies), liver diseases (6 studies), and neurological conditions (17 studies). This body of evidence provides important insights and also highlights the complexity of alcohol’s impact on health.

Cancers

The MR evidence showed clear and consistent associations between alcohol and certain cancers, particularly oral and oropharyngeal cancers, colorectal cancer, cutaneous melanoma, and liver cancer, especially hepatocellular carcinoma. For these cancers, alcohol appears to play a direct causal role, independent of smoking.

Other cancer sites showed more mixed results. For example, breast cancer did not show a significant association except when looking at problematic alcohol use, which contrasts with observational studies suggesting even light drinking increases risk. For esophageal cancer, results were inconsistent, but studies in Asian populations did support a higher risk, especially for esophageal squamous cell carcinoma. Some MR studies also suggested no clear associations with ovarian, prostate, gastric, pancreatic, bladder, thyroid, and kidney cancers, while endometrial cancer was unique in showing a potential protective effect in one subtype.

Overall, the MR evidence supports the carcinogenic role of alcohol for several cancers but also highlights important gaps and inconsistencies depending on cancer site, genetic background, and study design.

Cardiovascular Diseases

The relationship between alcohol and cardiovascular health has long been debated, with observational studies suggesting a protective effect of light to moderate drinking. However, MR studies largely challenge this view.

Our review showed robust associations between alcohol and increased blood pressure, hypertension, and stroke, with no evidence of cardiovascular protection, even at low levels of consumption. For heart failure, atrial fibrillation, and coronary artery disease, MR results were less consistent, but overall, they did not confirm the protective associations reported in earlier observational studies. This suggests that the so-called “cardioprotective” effect of moderate drinking may have been overstated due to confounding and methodological bias.

Liver Diseases

Although only six MR studies were available, their conclusions were strong: genetically predicted alcohol consumption markedly increases the risk of alcoholic liver disease and cirrhosis. The evidence also suggested possible detrimental effects in people with metabolic dysfunction-associated steatotic liver disease (MASLD), although findings were inconsistent. In addition, MR studies reported associations with impaired liver function biomarkers, supporting the role of alcohol in progressive liver injury.

Neurological Disorders

The MR evidence on brain health was more heterogeneous. Observational studies had suggested a J-shaped curve, with moderate drinkers having better outcomes than abstainers, but MR studies did not support this protective effect. Instead, results were mixed and often inconclusive, with some studies suggesting potential protective effects for Parkinson’s disease, but others pointing to harmful associations with Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, epilepsy, and cognitive decline. The methodological limitations of these studies (small sample sizes, overlapping cohorts, weak instruments) call for further research, but overall, the evidence does not confirm any neuroprotective role of alcohol.

Conclusion

Our systematic review of Mendelian Randomization (MR) studies underscores that alcohol consumption is causally linked to major health risks, including several cancers, hypertension, and stroke, while providing little to no protective effect—even at low levels of intake. These findings reinforce the urgent need for cautious public health messaging and evidence-based policies to reduce alcohol-related harm.

Beyond the specific case of alcohol, MR itself emerges as a powerful methodological tool for modern epidemiology. As we have seen, it offers robust evidence for causal inference, helping to resolve uncertainties and overcome many of the biases inherent to observational research. Leading scientific societies are increasingly incorporating MR findings into their clinical guidelines, as reflected in recent publications in journals such as the European Heart Journal.

With the rapid expansion of large-scale genetic databases and the availability of advanced statistical tools, MR is progressively establishing itself as a standard in epidemiological research.

In the long run, MR has the potential to become an essential instrument not only for advancing scientific understanding but also for shaping clinical recommendations and guiding public health strategies.

Preparing for the next EUSPR Conference (2026 in Dublin, Ireland)

Are you planning to participate in the next EUSPR Conference? If so, do you intend to present further details about your work?

Yes,I am planning to participate in the next EUSPR Conference in 2026. Whether I will present my work will depend on the thematic focus of next year’s conference and how it aligns with my current research activities.

About the author

I am a scientific studies manager working on the AlcoolConsoScience project coordinated by the French Society of Alcoholology and Addictology (SF2A), within a team of experts and physicians specialized in addictology. My research focuses on the health effects of alcohol consumption and its interaction with tobacco, with particular attention to neurological diseases, cancer, liver disease, cardiovascular conditions, and alcohol–drug interactions, which contribute to improving clinical practice and patient care. Within this project, I contribute to systematic reviews, data analysis, and the development of scientific syntheses aimed at strengthening the evidence base for public health communication. My work also supports the creation of educational and communication tools for healthcare professionals and the general public, developed by the SF2A communication team, with the overarching aim of improving knowledge, supporting prevention, and informing better care practices in the field of public health.

You can contact her at naourasbouajila97[at]gmail.com  for any enquiries

 


OpenEdition suggests that you cite this post as follows:
EUSPR Early Careers Forum (October 20, 2025). Can Our Genes Really Predict Our Disease Risk? Preventing disease and ill health. Retrieved May 19, 2026 from https://doi.org/10.58079/14zed


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