Is coffee good or bad for you?

Caffeinated coffee is a psychoactive substance, notes Sandra Sanchez-Loij, PhD, an associate professor of psychiatry at the University of California, San Diego School of Medicine, who is part of an international group of researchers who compared coffee consumption profiles from the 23andMe database with the larger British record. She is corresponding author of a study recently published in the journal Neuropsychiatry. Neuropsychopharmacology.

Dr. Haley HA Thorpe, from the Department of Anatomy and Cell Biology at the Schulich School of Medicine and Dentistry at Western University in Ontario, is lead author on the paper. Dr. Thorpe explained that the research team collected genetic data and self-reported coffee consumption to compile a genome-wide association study (GWAS) to uncover associations between genes known to be linked to coffee consumption and health-related traits and conditions.

“We used this data to identify genomic regions associated with a higher or lower likelihood of drinking coffee,” Thorpe explained, “and to identify the genes and biology underlying coffee consumption.”

Dr. Abraham Palmer, also the lead researcher on the paper and a professor of psychiatry at the University of California, San Diego School of Medicine, said most people are surprised to learn that there is a genetic influence on coffee intake. “From previous papers, we had ample reason to suspect that there might be genes that influence coffee intake,” he said. “So we weren't surprised to find statistical evidence that this is a genetic trait in both cohorts we studied. In other words, that certain genetic variants inherited from your parents influence how much coffee you drink.”

Sánchez Loigi said the genetic influence on coffee consumption is the first of two questions researchers want to answer.

“The second question is something that coffee lovers really want to know,” Sánchez Loigi says: “Is drinking coffee good or bad? Does drinking coffee have positive health consequences or not?”

The answer is inconclusive. A comparison of the group's genome-wide association study of 130,153 US-based 23andMe study participants with a similar UK Biobank database (334,649 Brits) revealed consistent positive genetic associations between coffee and adverse health outcomes such as obesity and drug use. A positive genetic association is an association between a particular gene variant (genotype) and a particular condition (phenotype). Conversely, a negative genetic association is an apparent protective trait that prevents a condition from developing. When it comes to mental illness, the results are even more complicated.

“For example, look at the genetics of anxiety, bipolar disorder and depression. In the 23andMe data set, they tend to be positively genetically correlated with the genetics of coffee consumption,” Thorpe says. “But in UK Biobank, we see the opposite pattern, they're negatively genetically correlated. This wasn't what we expected.”

There have been other instances where 23andMe sets didn't match with UK Biobank, but the biggest discrepancies were for mental illnesses, she said.

“It's common in this field to combine similar datasets to increase research power, and this information makes it pretty clear that combining these two datasets was not a smart idea, and we ended up not doing so,” Thorpe said. She explained that blending databases can mask effects, leading researchers to erroneous conclusions or even canceling each other out.

Sánchez-Loij says the researchers have a few ideas as to why the results differed. First, the surveys were apples-and-oranges. For example, the 23andMe survey asked, “How many 5-ounce (cup-sized) cups of caffeinated coffee do you drink per day?” Compare that to the UK Biobank's “How many cups of coffee do you drink per day (including decaffeinated coffee)?”

The study didn't take into account differences in how the coffee is served, beyond serving size and whether it's caffeinated or decaffeinated: “We know that in the UK, instant coffee is generally preferred, whereas in the US, ground coffee is more popular,” Thorpe said.

“And then there's Frappuccinos,” Sánchez-Loisi added, referring to the U.S. trend of drinking coffee loaded with sugar and additives. Palmer cited other caffeinated beverages, particularly tea, in the context of the UK Biobank, but tea was not included in the coffee-only GWAS. Palmer added that GWAS show genotype-phenotype associations that are different than those between coffee and tea.

“Genetics influence a lot of things – height, for example,” he says, “and those things probably work the same whether you live in the US or the UK. But coffee is something people decide.”

Sanchez Loigi noted that coffee comes in many forms, from instant coffee to Frappuccinos, and is consumed with different cultural norms in different places: someone with a particular genotype might end up with a completely different phenotype in the UK than in the US.

“And that's exactly what the data tells us,” she says, “because in the case of height, behavior doesn't really matter, but behavior and selection in the environment affect it in different ways. So genotype-by-environment interactions complicate the picture.”

The researchers stressed the need for further research to address not only coffee and caffeine consumption but also the use of other substances to elucidate the genetic and environmental relationships.

In addition to these researchers, co-authors on the paper from UC San Diego include Benjamin K. Pham, John J. Meredith, Mariella V. Jennings, Natasia S. Courchesne-Kulak, and Sevim B. Bianchi from the Department of Psychiatry. Additional co-authors include Pierre Fontanillas of 23andMe, Inc., Laura Villar-Ribot of Universitat Autònoma de Barcelona, ​​Spain, Julian Mutz of King's College London, UK, Sarah L. Elson and Gibran Y. Khokhar of the University of Guelph, Canada, Abdel Abdellaoui of the University of Amsterdam, The Netherlands, Lee K. Davis of Vanderbilt University Medical Center, and the 23andMe research team.

Mariela V. Jennings, Sevim B. Bianchi, and Sandra Sanchez-Roige are supported by funds from the California Tobacco Related Disease Research Program (TRDRP; grant numbers T29KT0526 and T32IR5226). Sevim B. Bianchi and Abraham Palmer are also supported by P50DA037844. BKP, Julian Mutz, and Sandra Sanchez-Roige are supported by NIH/NIDA DP1DA054394. Hayley H. A. Thorpe is funded through a Natural Sciences and Engineering Research Council PGS-D scholarship and a Canadian Institutes of Health Research (CIHR) fellowship. Jibran Y. Khokhar is supported by a CIHR Canada Translational Neuropsychopharmacology Fellowship. Lea K. Davis is supported by R01 MH113362. Natasia S. Courchesne-Krak is funded through a NeuroAIDs Interdisciplinary Research Fellowship (grant number R25MH081482). Julian Mutz is funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre, South London, Maudsley NHS Foundation Trust and King's College London.