Living in the city where the original Starbucks opened, Seattleites are no strangers to drinking coffee. During the hustle and bustle of everyday life, a cup of coffee can offer a boost of energy to keep people moving forward – an effect that has made it one of the most widely consumed and researched beverages in the world [1]. Interestingly, studies of frequent coffee drinkers find both beneficial and detrimental impacts of habitual consumption; for example, research suggests coffee consumption has preventative effects against diseases like Alzheimer’s and Parkinson’s, but also an increased risk of acquiring certain cancers and high blood pressure [1][2]. Although we know a great deal about coffee, the difference in effect from person to person makes it difficult to understand the full scope of the drink’s impact on human health, leading to the hypothesis that genetics play a main role [2]. Further examination of the variation in coffee consumption raises questions about the neurological mechanisms associated with the beverage and has led to findings that support a genetic basis for habitual coffee consumption.

To understand the potential genetic relationship involved in coffee consumption, it is important to understand how the drink affects the human body. The many different compounds that contribute to the makeup of coffee, such as caffeine, polyphenol, and niacin, make it a relatively complex beverage [2]. However, the energizing effect one feels after drinking coffee is primarily due to caffeine, a drug that stimulates the central nervous system. Caffeine acts as an antagonist of adenosine, receptors that inhibit the release of neurotransmitters [1]. By prohibiting adenosine’s signals via multiple mechanisms, caffeine produces an excitatory effect by activating a different pathway, which then leads to an increased release of dopamine, a neurotransmitter associated with the brain’s reward systems. The amount of caffeine necessary to produce a stimulating effect varies, but research suggests it is related to the frequency of consumption and a person’s genetic makeup [1].

By comparing the genomes of hundreds of individuals to the average number of cups of coffee they consumed per day, researchers have located a gene – known as PDSS2 – that shows a negative correlation with coffee consumption: the more coffee a person drinks, the less the gene is expressed [2]. When PDSS2 is inactivated in mice, the expression of genes involved in the metabolism of caffeine significantly increases, suggesting PDSS2 helps regulate those genes, thereby indirectly affecting cell metabolism [2]. The PDSS2 gene codes for an enzyme responsible for the synthesis of coenzyme Q10, which are molecules crucial for converting carbohydrates and fatty acids into energy to drive cellular processes [3]. The association between PDSS2 and coenzyme Q10 leads to further questions about how coffee affects the body’s metabolism; more specifically, how the prevalence of PDSS2 expression affects energy conversion [2]. The gene’s connection to the body’s caffeine mechanisms may help explain why different people require varying amounts of coffee to produce the same effect: a genetic predisposition to drink greater amounts of coffee could suggest a less efficient caffeine metabolism, thus more cups are necessary to acquire the stimulating effects [2].

Another recent study has identified six more loci—specific positions of genes on chromosomes—also supporting a relationship between genetics and frequency of coffee consumption [4]. The loci relate to coffee drinking in unique ways: two loci possibly affect consumption habits by altering the behavioral effects of caffeine by modulating neurotransmitters involved in mood-regulating circuits, such as dopamine and serotonin. The other four loci indirectly affect the metabolism process and consequently the amount of caffeine present in the body; two have been discovered previously, while the other two essentially remain mysteries. When each of the six loci were modified in mice, the resulting phenotypic abnormalities were all associated with coffee consumption [4]. These findings support a plausible genetic basis behind a person’s coffee drinking habits—the presence of these genes or lack thereof could be used to understand how people respond to caffeine or how much coffee a person requires in order to feel caffeine’s effects.

Although current research has yet to solidify the connection between these newly identified genes and a person’s coffee consumption habits, caffeine metabolism clearly plays an extremely important role in gaining a more complete understanding of their relationship. Learning more about the presence of these specific genes and their association with caffeine will allow us to better comprehend the molecular mechanisms behind drinking coffee and hopefully enable us to examine a person’s genetic makeup in order to improve our knowledge of the long-term effects of coffee consumption.


  1. Amin, N., Byrne, E., Johnson, J., Chenevix-Trench, G., Walter, S., Nolte, I. M., ... & Keers, J.C. (2012). Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Molecular psychiatry, 17(11), 1116-1129.
  2. Pirastu, N., Kooyman, M., Robino, A., van der Spek, A., Navarini, L., Amin, N., ... & Gasparini, P. (2016). Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption. Scientific Reports, 6.
  3. Crane, F. L. (2001). Biochemical functions of coenzyme Q10. Journal of the American College of Nutrition, 20(6), 591-598.
  4. Cornelis, M. C., Byrne, E. M., Esko, T., Nalls, M. A., Ganna, A., Paynter, N., ... & Ngwa, J. S. (2015). Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Molecular psychiatry, 20(5), 647-656.