Genetic Variants Influence Endocannabinoid System Gene Expression Differently Across Body Tissues

In 31,684 participants from eQTLGen, 22,020 genetic variants (eQTLs) influenced 43 of 70 selected ECS genes. Across 49 tissues in GTEx, 69 of 70 ECS genes had tissue-specific genetic effects. The female reproductive system had fewer eQTLs compared to other physiological systems. In the endometrium specifically, FABP3 (an endocannabinoid transporter) showed significant genetic effects, with 13 additional ECS genes showing FDR-significant eQTLs.

Analysis of publicly available genomic datasets: eQTLGen (31,684 participants, blood-based), GTEx (838 donors, 49 tissues), and an in-house endometrial dataset (206 samples). Examined genetic variant effects on expression of 70 endocannabinoid system genes.

Individual genetic differences in the endocannabinoid system may explain why people respond differently to cannabis. Understanding tissue-specific genetic effects is essential for developing targeted cannabinoid-based therapies.

This research explains a fundamental challenge in cannabinoid medicine: the same dose of cannabis or cannabinoid medication may have vastly different effects in different people because their genetic makeup influences how their endocannabinoid system functions in specific tissues.

Datasets are from European-ancestry-predominant populations. Gene expression does not necessarily reflect protein levels or receptor function. Endometrial samples are a small dataset. Cannot directly predict clinical cannabinoid response from eQTL data.