biostudies-literatureWoolf BEconomic and Social Research CouncilBritish Heart FoundationSwedish Heart Lung FoundationSouth West Doctoral Training PartnershipMedical Research CouncilBritish Heart Foundation Centre of Research ExcellenceSwedish Research CouncilUnited Kingdom Research and Innovation Medical Research CouncilWellcome TrustSwedish Research Council for Health, Working Life and Welfare1776-1784https://www.ebi.ac.uk/biostudies/studies/S-EPMC7616520biostudies-literatureUnknown193(12)Mendelian randomization is an epidemiologic technique that can explore the potential effect of perturbing a pharmacological target. Plasma caffeine levels can be used as a biomarker to measure the pharmacological effects of caffeine. Alternatively, this can be assessed using a behavioral proxy, such as average number of caffeinated drinks consumed per day. Either variable can be used as the exposure in a Mendelian randomization investigation, and to select which genetic variants to use as instrumental variables. Another possibility is to choose variants in gene regions with known biological relevance to caffeine level regulation. These choices affect the causal question that is being addressed by the analysis, and the validity of the analysis assumptions. Further, even when using the same American journal of epidemiologyComparison of caffeine consumption behavior with plasma caffeine levels as exposure measures in drug-target mendelian randomization.PMC76165202018-00123225790225790/Z/22/ZMC_UU_000011/7ES/P000630/1MC_UU_00040/1MC_UU_00002/72019-00977RE/18/4/3421520210351MC_UU_00011/7Gill DWoolf BCronje HTZagkos LBurgess SLarsson SCfalseComparison of caffeine consumption behavior with plasma caffeine levels as exposure measures in drug-target mendelian randomization.Mendelian randomization is an epidemiologic technique that can explore the potential effect of perturbing a pharmacological target. Plasma caffeine levels can be used as a biomarker to measure the pharmacological effects of caffeine. Alternatively, this can be assessed using a behavioral proxy, such as average number of caffeinated drinks consumed per day. Either variable can be used as the exposure in a Mendelian randomization investigation, and to select which genetic variants to use as instrumental variables. Another possibility is to choose variants in gene regions with known biological relevance to caffeine level regulation. These choices affect the causal question that is being addressed by the analysis, and the validity of the analysis assumptions. Further, even when using the same 2024-01-01T00:00:00Z2024 Dec2026-04-08T18:48:07.268Z2025-04-04T02:46:35.933ZS-EPMC76165203890443410.1093/aje/kwae143