Unraveling the genetics behind different levels of alcohol consumption

Researchers have delved deep into a vast dataset comprising over 3 million individuals, unearthing fascinating connections between genetic factors influencing alcohol consumption and their relationship with various health conditions.

The study, recently published in the Lancet eBioMedicine, highlights the complex interplay between genetics, alcohol consumption behaviors, and overall well-being.

Genetic landscape of alcohol consumption

Sandra Sanchez-Roige, Ph.D., associate professor at the University of California San Diego School of Medicine Department of Psychiatry, led the research group that analyzed genetic data from 23andMe, Inc., a direct-to-consumer genetics company.

The team focused on three specific single-nucleotide polymorphisms (SNPs) known to influence alcohol consumption. Abraham A. Palmer, Ph.D., professor and vice chair for basic research in the psychiatry department, emphasized the importance of classifying individuals based on their genetic ancestry to avoid statistical pitfalls.

“These variants are primarily associated with how much someone may consume alcohol,” explained Sanchez-Roige. “And they also tend to prevent alcohol use disorder, because these variants are primarily associated with the quantity of alcohol someone may drink.”

Protective power of rare variants

The researchers discovered that certain variants, or alleles, of the SNPs under study act as “protective” factors against excessive alcohol drinking and alcohol use disorder.

Interestingly, one of these alcohol-protective variants is exceptionally rare, with the most prevalent allele found in only 232 individuals out of the 2,619,939 European cohort, 29 out of the 446,646 Latin American cohort, and 7 out of the 146,776 African American cohort.

These protective variants influence how the body metabolizes ethanol, the intoxicating chemical in alcoholic beverages.

“The people who have the minor allele variant of the SNP convert ethanol to acetaldehyde very rapidly. And that causes a lot of negative effects,” said Sanchez-Roige. She likened the experience to a bad hangover that sets in almost immediately, overshadowing any pleasurable effects of alcohol.

Unexpected genetic connections to alcohol consumption

While the SNP variants’ influence on alcohol consumption is well-established, Sanchez-Roige and her team took a “hypothesis-free” approach to the 23andMe dataset.

They aimed to uncover potential associations between the three SNP variants and other traits and behaviors beyond alcohol consumption.

The researchers found that individuals with the alcohol-protective alleles generally enjoyed better health, including less chronic fatigue and less need for daily assistance with tasks.

However, the study also revealed some surprising and counterintuitive findings. Individuals with the alcohol-protective alleles reported higher rates of lifetime tobacco use, emotional eating, Graves’ disease, hyperthyroidism, malaria, myopia, skin cancer, lung cancer, and migraine with aura.

Chicken-and-egg dilemma

Sanchez-Roige acknowledged the complex nature of their findings, particularly when it comes to conditions known to be associated with alcohol consumption, such as cardiovascular disease.

“So is alcohol consumption leading to these conditions?” she asks. Palmer adds, “Or do these genetic differences influence traits like malaria and skin cancer in a manner that is independent of alcohol consumption?”

The researchers emphasized the importance of conducting broad, hypothesis-free studies on large, diverse datasets to gain a more comprehensive understanding of the genetic basis of alcohol behaviors and other conditions.

Sanchez-Roige stressed the significance of including individuals from different ancestral backgrounds in genetic studies to promote a more inclusive and accurate understanding of human health.

“The study of only one group of genetically similar individuals (for example, individuals of shared European ancestry) could worsen health disparities by aiding discoveries that will disproportionately benefit only that population,” she noted.

Implications and future research

This intriguing study opens numerous avenues for future research, encouraging scientists to investigate the potential connections between alcohol-protective alleles and conditions that seemingly have no direct link to alcohol consumption.

“Understanding the underlying mechanisms of these effects could have implications for treatments and preventative medicine,” Sanchez-Roige emphasized.

Respecting the genetic role in alcohol consumption

In summary, the study by Sanchez-Roige, Palmer, and their team has unveiled a complex tapestry of associations between genetic factors influencing alcohol consumption and various health outcomes.

By leveraging the power of a vast dataset from 23andMe, Inc., the researchers have confirmed the protective role of certain genetic variants against alcohol misuse and uncovered surprising connections to conditions seemingly unrelated to alcohol.

This study underscores the importance of conducting inclusive genetic research, embracing diverse ancestral backgrounds, and pursuing hypothesis-free approaches to unravel the intricate mechanisms underlying human health.

As scientists continue to explore the leads generated by this study, they inch closer to a future where genetic insights can inform personalized treatments and preventative strategies, ultimately benefiting individuals across the spectrum of human diversity.

The full study was published in the journal Lancet eBiomedicine.

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