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Sökning: WFRF:(Zagkos Loukas) > (2024) > Genetic investigati...

Genetic investigation into the broad health implications of caffeine : evidence from phenome-wide, proteome-wide and metabolome-wide Mendelian randomization

Zagkos, Loukas (författare)
Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
Cronje, Helene T. (författare)
Univ Copenhagen, Dept Publ Hlth, Sect Epidemiol, Copenhagen, Denmark.
Woolf, Benjamin (författare)
Univ Bristol, Sch Psychol Sci, Bristol, Gloucestershire, England.;Univ Bristol, Integrat Epidemiol Unit, Med Res Council, Bristol, England.;Univ Cambridge, Med Res Council, Biostat Unit, Cambridge, England.
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de La Harpe, Roxane (författare)
Univ Hosp Lausanne, Dept Med, Unit Internal Med, Lausanne, Switzerland.
Burgess, Stephen (författare)
Univ Cambridge, Med Res Council, Biostat Unit, Cambridge, England.
Mantzoros, Christos S. (författare)
Harvard Med Sch, Boston VA Healthcare Syst, Dept Med, Boston, MA USA.;Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA.
Elliott, Paul (författare)
Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, United Kingdom Dementia Res Inst, London, England.;Imperial Coll London, British Heart Fdn Ctr Res Excellence, London, England.
Yuan, Shuai (författare)
Karolinska Institutet,Inst Environm Med, Karolinska Inst, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.
Larsson, Susanna C. (författare)
Karolinska Institutet,Uppsala universitet,Medicinsk epidemiologi,Inst Environm Med, Karolinska Inst, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.
Tzoulaki, Ioanna (författare)
Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, United Kingdom Dementia Res Inst, London, England.;Imperial Coll London, British Heart Fdn Ctr Res Excellence, London, England.;Biomed Res Fdn, Acad Athens, Div Syst Biol, Athens, Greece.
Gill, Dipender (författare)
Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, British Heart Fdn Ctr Res Excellence, London, England.
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Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England Univ Copenhagen, Dept Publ Hlth, Sect Epidemiol, Copenhagen, Denmark. (creator_code:org_t)
BioMed Central (BMC), 2024
2024
Engelska.
Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 22:1
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • BackgroundCaffeine is one of the most utilized drugs in the world, yet its clinical effects are not fully understood. Circulating caffeine levels are influenced by the interplay between consumption behaviour and metabolism. This study aimed to investigate the effects of circulating caffeine levels by considering genetically predicted variation in caffeine metabolism.MethodsLeveraging genetic variants related to caffeine metabolism that affect its circulating levels, we investigated the clinical effects of plasma caffeine in a phenome-wide association study (PheWAS). We validated novel findings using a two-sample Mendelian randomization framework and explored the potential mechanisms underlying these effects in proteome-wide and metabolome-wide Mendelian randomization.ResultsHigher levels of genetically predicted circulating caffeine among caffeine consumers were associated with a lower risk of obesity (odds ratio (OR) per standard deviation increase in caffeine = 0.97, 95% confidence interval (CI) CI: 0.95—0.98, p = 2.47 × 10−4), osteoarthrosis (OR = 0.97, 95% CI: 0.96—0.98, P=1.10 × 10−8) and osteoarthritis (OR: 0.97, 95% CI: 0.96 to 0.98, P = 1.09 × 10−6). Approximately one third of the protective effect of plasma caffeine on osteoarthritis risk was estimated to be mediated through lower bodyweight. Proteomic and metabolomic perturbations indicated lower chronic inflammation, improved lipid profiles, and altered protein and glycogen metabolism as potential biological mechanisms underlying these effects.ConclusionsWe report novel evidence suggesting that long-term increases in circulating caffeine may reduce bodyweight and the risk of osteoarthrosis and osteoarthritis. We confirm prior genetic evidence of a protective effect of plasma caffeine on risk of overweight and obesity. Further clinical study is warranted to understand the translational relevance of these findings before clinical practice or lifestyle interventions related to caffeine consumption are introduced.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Näringslära (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Nutrition and Dietetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Caffeine
Phenome-wide association study
Mendelian randomization
Osteoarthritis
Obesity

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