Unlocking the genetic code of drinking

An exploration of 3 million records revealed links between genetic variants that control drinking and a host of non-alcohol-related diseases.

A research team centered on the University of California, San Diego School of Medicine dug into a data set of more than 3 million people compiled by direct-to-consumer genetics company 23andMe, Inc. and found a link between genetic factors that influence alcohol consumption. Interesting connections.

The research was recently published in Lancet eBiomedicine.

Genetic data analysis

The study used genetic data to broadly categorize individuals into European, Latino and African-American, explained corresponding author Dr. Sandra Sanchez-Roige, associate professor in the Department of Psychiatry at the University of California, San Diego School of Medicine. This classification “is necessary to avoid the pitfall of statistical genetics known as population stratification,” said paper co-author Abraham A. Palmer, Ph.D., professor of basic research and vice chair of the Department of Psychiatry.

Researchers analyzed genetic data from 3 million 23andMe study participants, focusing on three specific small snippets DNA Called a single nucleotide polymorphism (SNP). Variants, or alleles, of these specific SNPs can “protect” people from a variety of alcohol behaviors, from excessive drinking to alcohol use disorders, Sanchez-Roige explained.

Genetic variation and alcohol metabolism

One of the alcohol-protective variants they believe is very rare: The most common of the three alleles found in the study was present in 232 individuals in the European cohort of 2,619,939, 29 in the Latin American cohort of 446,646, and 146,776 in the Latin American cohort. Of the 7 African Americans. Others are more common. These variations affect how the body metabolizes ethanol, the intoxicating chemical in alcoholic beverages.

“People with the minor allele variant of the SNP are able to convert ethanol into acetaldehyde very quickly. This can cause a lot of negative effects,” Sanchez-Roic said. She went on to say that the resulting nausea overshadowed any pleasurable effects of the alcohol – think of the severe hangover that set in almost immediately.

“These variations are primarily related to how much a person drinks,” she said. “And they also tend to protect against alcohol use disorders because these variants are primarily related to the amount of alcohol someone is likely to drink.”

Wider effects of genetic variation

Sanchez-Roige explained that the impact of SNP variants on drinking has been well-studied, but her team took a “no hypothesis” approach with the 23andMe dataset, which contains survey data on thousands of traits and behaviors. The researchers wanted to see if these three single nucleotide polymorphism (SNP) variants had effects beyond drinking alcohol.

Sanchez-Roige and Palmer noted that their team has a 10-year partnership with 23andMe that focuses on numerous characteristics, especially those related to addiction. This work is the basis for academic collaborations in the 23andMe research program.

They data mined DNA analysis from saliva samples submitted by consenting 23andMe study participants, as well as responses to health and behavioral surveys available in the 23andMe database, and found a range of associations, though not necessarily related to alcohol. Individuals with alcohol-protective alleles generally have better health, including less chronic fatigue and needing less daily help completing daily tasks.

But the paper points out that individuals with alcohol-protective alleles also had poorer health in some aspects: more lifetime smoking, more emotional eating, more Graves’ disease and hyperthyroidism. Completely unexpected differences were also reported in individuals with alcohol-protective alleles, such as more malaria, myopia, and multiple cancers, particularly more skin and lung cancers, as well as more migraines with aura.

Health Associations and Genetic Insights

Sánchez-Roic admits that their discovery presents a chicken-and-egg problem. For example: cardiovascular disease is just one of many conditions known to be linked to alcohol consumption. “So does drinking alcohol cause these conditions?” she asked. Palmer concluded: “Or do these genetic differences affect traits such as malaria and skin cancer in a way that is independent of alcohol consumption?”

Sánchez-Roig said such broad, hypothesis-free studies are only possible if researchers have access to large amounts of data. Many datasets, including the one used in the study, rely heavily on individuals of European ancestry.

“Including individuals from diverse ancestral backgrounds in genetic studies is important because it allows for a more complete understanding of the genetic basis of alcohol behaviors and other conditions, all of which contributes to a more complete and accurate understanding of human health,” she said. “Studying only a group of genetically similar individuals (e.g., individuals with a common European ancestry) may exacerbate health disparities because the findings would only benefit that population disproportionately.”

Conclusion and future research directions

Their study opens many doors for future research to track possible associations between alcohol-protective alleles and conditions that are not clearly related to alcohol consumption, she said.

“Understanding the underlying mechanisms of these effects may have implications for therapeutic and preventive medicine,” Sanchez-Roic noted.

Reference: Mariela V. Jennings, José Jaime Martínez-Magaña, Natasia S. Courchesne-Krak, Renata B. Cupertino, “Panel-wide associations of variation in alcohol use in a diverse cohort of over 3 million people.” and Mendelian Randomization Studies,” Laura Vilar-Ribó, Sevim B. Bianchi, Alexander S. Hatoum, Elizabeth G. Atkinson, Paola Giusti-Rodriguez, Janitza L. Montalvo-Ortiz, Joel Gelernter, María Soler Artigas, Stella Aslibekyan, Adam Auton, Elizabeth Babalola, Robert K Bell, Jessica Bielenberg, Katarzyna Blake, Emily Bliss, Daniela Coker, Gabriel Cuellar · Partida, Devika Damija, Sayanthan Das, Sarah Elson, Nicholas Erickson, Theresa Fierstein, Allison Fey Chi, Kiper Frates-Brant, Pierre Fontanilas, Will Freeman, Julie M. Granka, Karl Heilbron, Alejandro Hernandez, Barry Hicks, David A. Hinds, Ethan M. Jewett, Yunxuan Jiang, Katelyn Kukar, Alan Kwong, Keng-Han Lin, Bianca A. Llamas, Maya Lowe, Jey C. McCreight, Matthew H. McIntyre, Steven J. Micheletti , Megan E. Moreno, Priyanka Nandakumar, Dominic T. Nguyen, Elizabeth S. Noblin, Jared O’Connell, Aaron A. Petra Kowitz, G. David Poznik, Alexandra Reynoso, Morgan Schumacher, Anjali J. Shastri, Janie F. Shelton, Jingchunzi Shi, Suyash Shringarpure, Qiaojuan Jane Su, Susana A. Tat, Christophe Toukam Tchakouté, Vinh Tran, Joyce Y. Tung, Xin Wang, Wei Wang, Catherine H. Weldon, Peter Wilton, Corinna D. Wong, Sarah L. Elson, Howard J. Edenberg, Pierre Fontanillas, Abraham A. Palmer With Sandra Sanchez-Roige, April 4, 2024 electronic biomedicine.
DOI: 10.1016/j.ebiom.2024.105086

Co-authors on the paper from the Department of Psychiatry at the University of California, San Diego School of Medicine include Mariela V. Jennings, Natasia S. Courchesne-Krak, Renata B. Cupertino and Sevim B. Bianchi. Sandra Sanchez-Roige is also affiliated with the Department of Medicine, Division of Genetic Medicine, Vanderbilt University.

Other co-authors are: José Jaime Martínez-Magaña, Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine; Laura Vilar-Ribó, Psychiatry, Mental Health and Addiction Group, Psychiatric Genetics Group, Hebron Valley Institute, Universitat Autònoma of Barcelona, ​​Barcelona, ​​Spain; Alexander S. Hatoum, Psychology, Washington University in St. Louis and Department of Brain Sciences; Elizabeth G. Atkinson, Department of Molecular and Human Genetics, Baylor College of Medicine; Paula Giusti Rodriguez, Department of Psychiatry, University of Florida School of Medicine; Janitza L. Montalvo-Ortiz, Department of Psychiatry, Department of Human Genetics, Yale University School of Medicine, National Center for Post-Traumatic Stress Disorder, VA CT Medical Center; Joel Gelernter, Department of Psychiatry, VA CT Medical Center, West Haven CT; and the Department of Psychiatry, Genetics, and Neuroscience at Yale University. School of Medicine; María Soler Artigas, Group of Psychiatry, Mental Health and Addiction, Psychiatry, Mental Health and Addiction, Institute of the Hebron Valley, Universitat Autònoma of Barcelona, ​​Barcelona, ​​Spain; Department of Mental Health, University Hospital of the Hebron Valley, Barcelona ; Center for Biomedical Network Research in Mental Health (CIBERSAM), Madrid; Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona; Howard J. Edenberg, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine; and 23andMe Inc . Research team including Sarah L. Elson and Pierre Fontanillas.

The research was funded in part by Tobacco-Related Diseases Research Program grants T32IR5226 and 28IR-0070, NIH National Institute on Drug Abuse (NIDA) DP1DA054394, and NIH National Institute of Mental Health (NIMH) R25MH081482.