Abstract
Background
Caffeine exposure modifies the turnover of monoamine neurotransmitters, which play a role in several neuropsychiatric disorders. We conducted a Mendelian randomization study to investigate whether higher plasma caffeine levels are causally associated with the risk of anorexia nervosa, bipolar disorder, major depressive disorder (MDD), and schizophrenia.
Methods
Summary-level data on the neuropsychiatric disorders were obtained from large-scale genome-wide association studies (GWASs) of European ancestry participants (n = 72,517 to 807,553) and meta-analyzed with the corresponding data from the FinnGen study (n = 356,077). Summary-level data on plasma caffeine were extracted from a GWAS meta-analysis of 9876 European ancestry individuals. The Mendelian randomization analyses estimated the Wald ratio for each genetic variant and meta-analyzed the variant-specific estimates using multiplicative random effects meta-analysis.
Results
After correcting for multiple testing, genetically predicted higher plasma caffeine levels were associated with higher odds of anorexia nervosa (odds ratio [OR] = 1.124; 95% confidence interval [CI] = 1.024–1.238, pFDR = 0.039) and a lower odds of bipolar disorder (OR = 0.905, 95% CI = 0.827–0.929, pFDR = 0.041) and MDD (OR = 0.965, 95% CI = 0.937–0.995, pFDR = 0.039). Instrumented plasma caffeine levels were not associated with schizophrenia (OR = 0.986, 95% CI = 0.929–1.047, pFDR = 0.646).
Conclusions
These Mendelian randomization findings indicate that long-term higher plasma caffeine levels may lower the risk of bipolar disorder and MDD but increase the risk of anorexia nervosa. These results warrant further research to explore whether caffeine consumption, supplementation, or abstinence could render clinically relevant therapeutic or preventative psychiatric effects.
Caffeine exposure modifies the turnover of monoamine neurotransmitters, which play a role in several neuropsychiatric disorders. We conducted a Mendelian randomization study to investigate whether higher plasma caffeine levels are causally associated with the risk of anorexia nervosa, bipolar disorder, major depressive disorder (MDD), and schizophrenia.
Methods
Summary-level data on the neuropsychiatric disorders were obtained from large-scale genome-wide association studies (GWASs) of European ancestry participants (n = 72,517 to 807,553) and meta-analyzed with the corresponding data from the FinnGen study (n = 356,077). Summary-level data on plasma caffeine were extracted from a GWAS meta-analysis of 9876 European ancestry individuals. The Mendelian randomization analyses estimated the Wald ratio for each genetic variant and meta-analyzed the variant-specific estimates using multiplicative random effects meta-analysis.
Results
After correcting for multiple testing, genetically predicted higher plasma caffeine levels were associated with higher odds of anorexia nervosa (odds ratio [OR] = 1.124; 95% confidence interval [CI] = 1.024–1.238, pFDR = 0.039) and a lower odds of bipolar disorder (OR = 0.905, 95% CI = 0.827–0.929, pFDR = 0.041) and MDD (OR = 0.965, 95% CI = 0.937–0.995, pFDR = 0.039). Instrumented plasma caffeine levels were not associated with schizophrenia (OR = 0.986, 95% CI = 0.929–1.047, pFDR = 0.646).
Conclusions
These Mendelian randomization findings indicate that long-term higher plasma caffeine levels may lower the risk of bipolar disorder and MDD but increase the risk of anorexia nervosa. These results warrant further research to explore whether caffeine consumption, supplementation, or abstinence could render clinically relevant therapeutic or preventative psychiatric effects.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 296 |
| Tidsskrift | BMC Medicine |
| Vol/bind | 21 |
| Udgave nummer | 1 |
| Antal sider | 8 |
| ISSN | 1741-7015 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:Open access funding provided by Uppsala University. B.W. is funded by an Economic and Social Research Council (ESRC) South West Doctoral Training Partnership (SWDTP) 1 + 3 PhD Studentship Award (ES/P000630/1) and a member of the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/7). H.T.C. is supported by the Novo Nordic Foundation Challenge Programme: Harnessing the Power of Big Data to Address the Societal Challenge of Aging (NNF17OC0027812). D.G. is supported by the British Heart Foundation Centre of Research Excellence (RE/18/4/34215) at Imperial College. S.C.L. is supported by the Swedish Research Council for Health, Working Life and Welfare (Forte, 2018–00123); Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351); the Swedish Cancer Society (Cancerfonden) and Swedish Research Council (Vetenskapsrådet, 2019–00977). S.B. is supported by the Wellcome Trust (225790/Z/22/Z) and the United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7). This research was supported by the National Institute for Health Research Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care.
Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.