Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization
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 ner...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-023-03008-0 |
| _version_ | 1827634011029110784 |
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| author | Benjamin Woolf Héléne T. Cronjé Loukas Zagkos Stephen Burgess Dipender Gill Susanna C. Larsson |
| author_facet | Benjamin Woolf Héléne T. Cronjé Loukas Zagkos Stephen Burgess Dipender Gill Susanna C. Larsson |
| author_sort | Benjamin Woolf |
| collection | DOAJ |
| description | 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, p FDR = 0.039) and a lower odds of bipolar disorder (OR = 0.905, 95% CI = 0.827–0.929, p FDR = 0.041) and MDD (OR = 0.965, 95% CI = 0.937–0.995, p FDR = 0.039). Instrumented plasma caffeine levels were not associated with schizophrenia (OR = 0.986, 95% CI = 0.929–1.047, p FDR = 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. |
| first_indexed | 2024-03-09T15:07:28Z |
| format | Article |
| id | doaj.art-045b80c6e72f4eab8f0f9f87bca751ba |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-03-09T15:07:28Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-045b80c6e72f4eab8f0f9f87bca751ba2023-11-26T13:33:50ZengBMCBMC Medicine1741-70152023-08-012111810.1186/s12916-023-03008-0Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomizationBenjamin Woolf0Héléne T. Cronjé1Loukas Zagkos2Stephen Burgess3Dipender Gill4Susanna C. Larsson5School of Psychological Science, University of BristolDepartment of Public Health, Section of Epidemiology, University of CopenhagenDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonMRC Biostatistics Unit at the University of CambridgeDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonUnit of Medical Epidemiology, Department of Surgical Sciences, Uppsala UniversityAbstract 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, p FDR = 0.039) and a lower odds of bipolar disorder (OR = 0.905, 95% CI = 0.827–0.929, p FDR = 0.041) and MDD (OR = 0.965, 95% CI = 0.937–0.995, p FDR = 0.039). Instrumented plasma caffeine levels were not associated with schizophrenia (OR = 0.986, 95% CI = 0.929–1.047, p FDR = 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.https://doi.org/10.1186/s12916-023-03008-0Anorexia nervosaBipolar disorder caffeineCoffeeDepressionMendelian randomizationSchizophrenia |
| spellingShingle | Benjamin Woolf Héléne T. Cronjé Loukas Zagkos Stephen Burgess Dipender Gill Susanna C. Larsson Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization BMC Medicine Anorexia nervosa Bipolar disorder caffeine Coffee Depression Mendelian randomization Schizophrenia |
| title | Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization |
| title_full | Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization |
| title_fullStr | Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization |
| title_full_unstemmed | Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization |
| title_short | Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization |
| title_sort | appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through mendelian randomization |
| topic | Anorexia nervosa Bipolar disorder caffeine Coffee Depression Mendelian randomization Schizophrenia |
| url | https://doi.org/10.1186/s12916-023-03008-0 |
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