Study reveals genetic associations between coffee and harmful health outcomes such as obesity and substance use

Scientists have found consistent positive genetic correlations of coffee intake with substance use and obesity in US and UK adults of European ancestry. The study is published in the journal Neuropsychopharmacology.

Background

Coffee is one of the most popular beverages worldwide, with 60-85% of European and US adults consuming 0.6 – 5.5 cups of coffee daily. Caffeine is the major psychoactive compound in coffee.

Bioactive compounds present in coffee are known to increase cognitive function and reduce the risk of several health complications, including liver disease, neurodegenerative diseases, cardiovascular disease, type 2 diabetes, and certain cancers.

Excessive coffee intake, in contrast, has been found to increase the risks of other substance use and misuse, abnormal lipid profile, pregnancy loss, gastrointestinal complications, and cardiovascular impairment.

Previous genetic studies have found that coffee intake is 36-56% heritable, indicating that coffee intake is amenable to genetic analysis. Several genome-wide association studies of coffee intake have found associations with single nucleotide polymorphisms (SNPs) within or near genes that metabolize caffeine. 

In this study, scientists have performed a genome-wide association study of coffee intake in 10,156 US participants of European ancestry. They have used genetic correlations and phenome- and laboratory-wide association studies to explore the relationships of coffee intake with multiple biomarkers, health characteristics, and lifestyle traits.

Furthermore, they have compared their findings with the largest available genome-wide association studies of coffee intake from the UK Biobank. They have used these datasets to explore cohort-specific associations with coffee intake across two different populations.

Important observations

The genome-wide association study of coffee intake in US participants identified seven significant loci (specific gene location on a chromosome), mostly in genes associated with metabolic processes.

A significant enrichment of coffee-related genes was observed in the central nervous system. The majority of observed genetic associations of coffee intake were with adverse outcomes in both US and UK cohorts, especially with substance use and obesity-related traits.

The gene-based analysis identified 165 candidate genes, including four previously identified coffee intake-related genes and six novel candidate genes.

The consistent positive genetic association observed between coffee intake and substance use highlights the widely accepted fact of having common genetic factors for any substance use. Existing literature clearly indicates that the use of one substance can potentially increase the use of any other substance.

A consistent positive genetic association was also observed between coffee intake and obesity-related traits in both US and UK cohorts. This finding contradicts previous meta-analyses of randomized controlled trials and epidemiological studies that have found modest inverse associations of coffee intake with body mass index (BMI) or non-specific impact of coffee intake on waist circumference and obesity.

Such discrepancies in findings could be attributed to the differences in coffee intake amount between studies, as higher coffee intake is likely to reduce its genetic associations with BMI and obesity. The scientists believe that future subgroup analyses may help explain contradictory associations between the genetics and prevalence of coffee intake with obesity-related traits.       

Regarding other health outcomes, the study found positive genetic associations of coffee intake with psychiatric disorders, pain, and gastrointestinal traits in the US cohort. However, these associations were either absent or negative in the UK cohort.

Similarly, a positive and a negative genetic association was observed between coffee intake and cognition in the UK cohort and the US cohort, respectively. Overall, the number of positive genetic associations between coffee intake and different health outcomes was higher and stronger in the US cohort compared to the UK cohort.

As mentioned by the scientists, cultural variation in coffee intake habits between the US and the UK could be attributed to the observed inconsistencies in genetic relationships. Moreover, comparatively higher levels of coffee intake or caffeine intake from high-caloric beverages have been documented in the US. This might explain the observed negative impact of coffee intake on health outcomes in the US cohort. 

Study significance

The study reveals that coffee intake is genetically associated with the risk of other substance use and obesity-related traits. These associations are observed in two large cohorts of European ancestry.

These findings provide a cautionary perspective on combining large datasets derived from distinct geo-cultural populations.

As mentioned by the scientists, the study used self-reported coffee intake data and captured a broad phenotype. Inter-individual differences in coffee cultivation or brewing methods, dietary and other lifestyle habits, and environmental and social norms related to coffee intake may act as potential confounding factors and contribute to the observed differences between cohorts.

The coffee intake phenotype in the US cohort was 5-ounce cups of caffeinated coffee, whereas, in the UK cohort, it was mostly decaffeinated coffee with no explicitly defined cup volume. These factors might also contribute to the discrepant genetic associations.