Genetic predisposition to coffee consumption and the association with the early risk of atherosclerosis.

Observational analysis showed no significant association between self-reported coffee consumption and subclinical atherosclerosis measures.

• Study included 24,835 participants from the Swedish CArdioPulmonary bioImage Study (SCAPIS).
• No significant associations were found between coffee intake and segment involvement score (SIS), coronary artery calcium score (CACS), or carotid plaques.
• Coffee intake was assessed via self-reported questionnaires.

Both one-sample and two-sample Mendelian randomization analyses showed an association between genetic predisposition to higher coffee consumption and increased segment involvement score (SIS).

• One-sample MR was conducted using SCAPIS data (n=24,835).
• Two-sample MR used both SCAPIS and UK Biobank data.
• The association was specifically with SIS (a measure of coronary atherosclerosis extent) rather than CACS or carotid plaques.
• Genetic predisposition to higher coffee consumption, not self-reported intake, drove the association.

Among individuals consuming coffee more than twice daily, two SNPs in AHR and CYP1A1/CYP1A2 genes were correlated with segment involvement score.

• Stratification analyses explored differences in genetic associations across varying coffee consumption levels.
• The two coffee consumption-associated SNPs identified were located in the AHR gene and the CYP1A1/CYP1A2 gene region.
• The correlation with SIS was observed specifically in the subgroup of frequent coffee drinkers (more than twice daily).
• These SNPs are known to be involved in caffeine metabolism.

Integrative metabolomics analysis identified lipid-related metabolites associated with the genetic proxy of coffee consumption.

• Lipid-related metabolites identified included triglycerides, phospholipids, and free cholesterol.
• These metabolites were associated with the genetic proxy of coffee consumption rather than self-reported intake.
• Findings suggest a potential lipid-mediated biological pathway linking genetically influenced coffee consumption to atherosclerosis risk.

Integrative proteomics analysis identified inflammation-related proteins associated with the genetic proxy of coffee consumption.

• Inflammation-related proteins identified included DLK1, IL1RL2, and CCL17.
• These proteins were associated with the genetic proxy of coffee consumption.
• The identification of inflammatory proteins suggests a potential inflammation-mediated pathway linking genetically influenced coffee consumption to coronary atherosclerosis.

Atherosclerosis was assessed using multiple imaging-based measures in the SCAPIS cohort.

• Measures included segment involvement score (SIS), coronary artery calcium score (CACS), and carotid plaque assessment.
• The study focused on subclinical (early-stage) atherosclerosis.
• SCAPIS is a Swedish population-based cohort study with 24,835 participants.