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Comparison of caffeine consumption behavior with plasma caffeine levels as exposure measures in drug-target Mendelian randomization.
Woolf, Benjamin; Cronjé, Héléne T; Zagkos, Loukas; Larsson, Susanna C; Gill, Dipender; Burgess, Stephen.
Afiliação
  • Woolf B; School of Psychological Science, University of Bristol, Bristol, UK.
  • Cronjé HT; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Zagkos L; MRC Biostatistics Unit at the University of Cambridge, Cambridge, UK.
  • Larsson SC; Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark.
  • Gill D; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
  • Burgess S; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Am J Epidemiol ; 2024 Jun 20.
Article em En | MEDLINE | ID: mdl-38904434
ABSTRACT
Mendelian randomization is an epidemiological 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 genetic variants, the sign of Mendelian randomization estimates (positive or negative) can change depending on the choice of exposure. Some genetic variants that decrease caffeine metabolism associate with higher levels of plasma caffeine, but lower levels of caffeine consumption, as individuals with these variants require less caffeine consumption for the same physiological effect. We explore Mendelian randomization estimates for the effect of caffeine on body mass index, and discuss implications for variant and exposure choice in drug target Mendelian randomization investigations.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Am J Epidemiol Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Am J Epidemiol Ano de publicação: 2024 Tipo de documento: Article