Health (Commonwealth Union) – A team based at the University of California San Diego School of Medicine delved deep into a vast dataset of over 3 million individuals provided by the direct-to-consumer genetics company 23andMe, Inc. Their investigation showed the intriguing links between genetic factors influencing alcohol consumption and their association with other disorders.
Published in the Lancet eBioMedicine, the study was spearheaded by Sandra Sanchez-Roige, Ph.D., who is an associate professor at UC San Diego School of Medicine Department of Psychiatry and the corresponding author. They utilized genetic data to categorize individuals broadly into European, Latin American, and African American groups, a crucial step to circumvent a statistical genetics challenge known as population stratification, as emphasized by co-author Abraham A. Palmer, Ph.D., professor and vice chair for basic research in the psychiatry department.
Scrutinizing the genetic profiles of the 3 million participants from 23andMe, the researchers zoomed in on three specific DNA segments called single-nucleotide polymorphisms (SNPs). These SNPs, according to Sanchez-Roige, harbor variants or alleles that exhibit a “protective” role against various alcohol-related behaviors, ranging from excessive drinking to alcohol use disorder.
Among the alcohol-protective variants under examination, one stood out for its rarity. The most prevalent allele among the three identified in the study was detected in 232 individuals from the European cohort out of 2,619,939 participants, in 29 individuals from the Latin American cohort out of 446,646, and in 7 individuals from the African American cohort out of 146,776. Other variants were more widespread. These genetic variations influence the body’s ethanol metabolism, the chemical responsible for the intoxicating effects of alcoholic beverages.
Sanchez-Roige indicated that individuals with the minor allele variant of the SNP metabolize ethanol into acetaldehyde at a swift pace. This rapid conversion leads to numerous adverse effects. She further elaborated that the consequent nausea overshadows any enjoyable aspects of alcohol consumption, akin to experiencing an immediate and severe hangover.
“These variants are primarily associated with how much someone may consume alcohol,” she explained. “And they also tend to prevent alcohol use disorder, because these variants are primarily associated with the quantity of alcohol someone may drink.”
Sanchez-Roige elucidated that while previous research has extensively studied the influence of SNP variants on alcohol consumption, her team adopted a “hypothesis-free” approach to explore the expansive 23andMe dataset, encompassing thousands of traits and behaviors. Their aim was to uncover any potential effects of the three SNP variants that goes beyond alcohol consumption.
Additionally, Sanchez-Roige and Palmer highlighted their decade-long collaboration with 23andMe, emphasizing their focus on various traits, particularly those relevant to addiction. This collaboration forms the foundation of an academic partnership under the 23andMe Research Program.
Through meticulous analysis of DNA from saliva samples provided by consenting 23andMe participants, along with the corresponding health and behavior surveys within the database, they unearthed a range of associations unrelated to alcohol. Notably, the individuals that had the alcohol-protective alleles exhibited generally improved health, experiencing less chronic fatigue as well as requiring less daily assistance with tasks.
The research highlights that individuals carrying alcohol-protective alleles may experience adverse health outcomes in certain domains. These include heightened lifetime tobacco use, increased tendencies toward emotional eating, and higher incidences of Graves’ disease and hyperthyroidism. Surprisingly, those with these alleles also exhibited unexpected differences, such as elevated rates of malaria, myopia, and various cancers, notably skin and lung cancers, along with an increased prevalence of migraine with aura.
Sanchez-Roige and her team recognize the complexity of their findings, acknowledging a potential chicken-and-egg scenario. For instance, while cardiovascular disease is linked with alcohol consumption, it remains unclear whether alcohol intake precipitates these conditions or if genetic variations independently influence traits like malaria and skin cancer.
The scope of such comprehensive, hypothesis-free investigations relies heavily on access to vast datasets, often drawn from individuals of European descent, as exemplified by the dataset employed in this study.
“It is important to include individuals from different ancestral backgrounds in genetic studies because it provides a more complete understanding of the genetic basis of alcohol behaviors and other conditions, all of which contributes to a more inclusive and accurate understanding of human health,” she added. “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 expressed that their study paves the way for extensive future research, exploring potential links between alcohol-protective alleles and conditions seemingly unrelated to alcohol consumption.
