A research group centered at the University of California, San Diego School of Medicine delved into a data set of more than 3 million individuals compiled by direct-to-consumer genetics company 23andMe, Inc., and found intriguing connections between genetic factors that influence alcohol consumption. and its relationship with other disorders.
The study was recently published in the Lancet eBioMedicine.
Sandra Sánchez-Roige, Ph.D., corresponding author and associate professor in the Department of Psychiatry at UC San Diego School of Medicine, explained that the study used genetic data to broadly classify individuals as European, Latin American, and African American. These classifications “are necessary to avoid a statistical genetics error called population stratification,” said co-author Abraham A. Palmer, Ph.D., professor and vice chair of basic research in the department of psychiatry.
Researchers analyzed genetic data from 23andMe’s 3 million research participants, focusing on three specific small fragments of DNA known as single nucleotide polymorphisms, or SNPs. Sánchez-Roige explained that variants, or alleles, of these particular SNPs are “protective” against a variety of alcohol behaviors, from excessive alcohol consumption to alcohol use disorder.
One of the protective alcohol variants they considered is very rare: the most prevalent among the three alleles found in the study appeared in 232 individuals from the European cohort of 2,619,939, 29 from the Latin American cohort of 446,646 and in 7 of the 146,776 African Americans. cluster; others are much more common. These variants affect how the body metabolizes ethanol, the intoxicating chemical in alcoholic beverages.
“People who have the minor allele variant of the SNP convert ethanol to acetaldehyde very quickly. And that causes a lot of negative effects,” Sánchez-Roige said. He went on to say that the resulting nausea overshadows any pleasurable effects of alcohol; Think of a bad hangover that appears almost immediately.
“These variants are mainly associated with the amount of alcohol a person can consume,” he said. “And they also tend to prevent alcohol use disorder, because these variants are primarily associated with how much alcohol someone can drink.”
Sánchez-Roige explained that the influence of SNP variants on alcohol consumption is well researched, but his group took a “hypothesis-free” approach to the 23andMe data set, which contains survey data on thousands of traits and behaviors. The researchers wanted to know if the three SNP variants could have other effects beyond alcohol consumption.
Sanchez-Roige and Palmer noted that their group has developed a 10-year partnership with 23andMe that has focused on numerous traits, especially those with relevance to addiction. This work is the basis of an academic collaboration through the 23andMe Research Program.
They extracted data from DNA analyzes of saliva samples submitted by consenting 23andMe research participants, as well as responses to health and behavioral surveys available in the 23andMe database, and found a constellation of associations, not necessarily related to alcohol. People with the alcohol-protective alleles had better overall health, including less chronic fatigue and needed less daily assistance with daily tasks.
But the paper notes that individuals with protective alcohol alleles also had worse health outcomes in certain areas: more lifetime tobacco use, more emotional eating, more Graves’ disease and hyperthyroidism. Individuals with protective alcohol alleles also reported completely unexpected differences, including more malaria, more myopia, and several types of cancer, particularly more skin and lung cancer, and more migraines with aura.
Sánchez-Roige acknowledged that his findings have a chicken-and-egg aspect. For example: cardiovascular disease is just one of several diseases known to be associated with alcohol consumption. “So, does alcohol consumption lead to these conditions?” she asks. Palmer concludes the thought: “Or do these genetic differences influence traits like malaria and skin cancer in a way independent of alcohol consumption?”
Sánchez-Roige said such large, hypothesis-free studies are only possible if researchers have access to very large data sets. Many data sets, including the one used in the study, rely heavily on people of European ancestry.
“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,” he said. . “Studying just a 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.”
He said his study opens numerous doors for future research, looking for possible connections between alcohol-protective alleles and conditions that have no apparent connection to alcohol consumption.
“Understanding the underlying mechanisms of these effects could have implications for treatments and preventive medicine,” Sánchez-Roige said.
Co-authors of the paper from the Department of Psychiatry at the University of California, San Diego School of Medicine are Mariela V. Jennings, Natasia S. Courchesne-Krak, Renata B. Cupertino and Sevim B. Bianchi. Sandra Sánchez-Roige is also associated with the Department of Medicine, Division of Genetic Medicine at Vanderbilt University.
Other co-authors are: José Jaime Martínez-Magaña, Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine; Laura Vilar-Ribó, Psychiatric Genetics Unit, Psychiatry, Mental Health and Addictions Group, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; Alexander S. Hatoum, Department of Psychology and Brain Sciences, Washington University in St. Louis; Elizabeth G. Atkinson, Department of Molecular and Human Genetics, Baylor College of Medicine; Paola Giusti-Rodríguez, Department of Psychiatry, University of Florida College of Medicine; Janitza L. Montalvo-Ortiz, Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, National Center for Post-Traumatic Stress Disorder, VA CT Health Care Center; Joel Gelernter, VA CT Health Care Center, Department of Psychiatry, West Haven CT; and Departments of Psychiatry, Genetics and Neuroscience, Yale University. Medicine School; María Soler Artigas, Psychiatric Genetics Unit, Psychiatry, Mental Health and Addictions Group, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Mental Health, Vall d’Hebron University Hospital, Barcelona; Center for Networked Biomedical Research in Mental Health (CIBERSAM), Madrid; and Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona; Howard J. Edenberg, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine; and the 23andMe Inc. research team, including Sarah L. Elson and Pierre Fontanillas.
The study was funded, in part, by Tobacco-Related Diseases Research Program Grants T32IR5226 and 28IR-0070, the National Institutes of Health (NIH), the National Institute on Drug Abuse (NIDA) DP1DA054394, and the Institute National Mental Health (NIMH) R25MH081482. .