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Genomics and personalized strategies in nutrition

Genetically predicted coffee and tea consumption and risk of intracranial aneurysm



Observational studies have shown associations between coffee and tea consumption and risk of intracranial aneurysm (IA). However, the results are not consistent. We conducted a Mendelian randomization study to clarify whether genetically predicted coffee and tea consumption has a causal effect on IA and its subtypes.


Genetic variants associated with coffee and tea consumption (cups/day) were obtained from large genome-wide association studies (GWASs), up to 349,376 subjects. Summary-level data for IA were adopted from a GWAS in 79,429 subjects (23 cohorts, 7495 cases, and 71,934 controls).


Genetically predicted coffee consumption was associated with a higher risk of any IA and aneurysmal subarachnoid hemorrhage (SAH), but not with unruptured IA. The ORs per 1 cup/day increase in genetically predicted coffee consumption were 1.42 (95% CI: 1.09–1.86; P = 0.010) for IA, 1.51 (95% CI: 1.13–2.03; P = 0.005) for aneurysmal SAH, and 1.20 (95% CI: 0.74–1.96; P = 0.460) for unruptured IA. Genetically predicted tea consumption was not associated with risk of any IA and its subtypes (P > 0.05). The associations remained consistent in sensitivity analyses, and no evidence of pleiotropy was detected.


Our study provides evidence to support that coffee consumption may increase the risk of IA and associated hemorrhage. Coffee should be limited for those at high risk of IA and associated hemorrhage.

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Fig. 1: Study design and data sources used in the present study.
Fig. 2: Association of genetically predicted coffee consumption with intracranial aneurysm.
Fig. 3: Association of genetically predicted coffee consumption with aneurysmal subarachnoid hemorrhage.

Data availability

The data that supports the findings of this study are available in Supplementary Table 1.


  1. Macdonald RL, Schweizer TA. Spontaneous subarachnoid haemorrhage. Lancet (London, England). 2017;389:655–66.

    Article  PubMed  Google Scholar 

  2. Vlak MHM, Rinkel GJE, Greebe P, van der Bom JG, Algra A. Trigger factors and their attributable risk for rupture of intracranial aneurysms: a case-crossover study. Stroke. 2011;42:1878–82.

    Article  PubMed  Google Scholar 

  3. Okamoto K, Horisawa R. The joint effect of oxidative stress and antioxidants on the risk of an aneurysmal rupture subarachnoid hemorrhage: a case-control study in Japan. Ann Epidemiol. 2007;17:359–63.

    Article  PubMed  Google Scholar 

  4. Okamoto K. Habitual green tea consumption and risk of an aneurysmal rupture subarachnoid hemorrhage: a case-control study in Nagoya, Japan. Eur J Epidemiol. 2006;21:367–71.

    Article  PubMed  Google Scholar 

  5. Burgess S, Bowden J, Fall T, Ingelsson E, Thompson SG. Sensitivity analyses for robust causal inference from mendelian randomization analyses with multiple genetic variants. Epidemiology. 2017;28:30–42.

    Article  PubMed  Google Scholar 

  6. Bakker MK, van der Spek RAA, van Rheenen W, Morel S, Bourcier R, Hostettler IC, et al. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet. 2020;52:1303–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cornelis MC, Byrne EM, Esko T, Nalls MA, Ganna A, Paynter N, et al. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Mol Psychiatry. 2015;20:647–56.

    Article  CAS  PubMed  Google Scholar 

  8. Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.

    Article  PubMed  Google Scholar 

  9. Wang M, Bai Y, Wang Z, Zhang Z, Liu D, Lian X. Higher tea consumption is associated with decreased risk of small vessel stroke. Clin Nutr. 2021;40:1430–35.

    Article  PubMed  Google Scholar 

  10. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44:512–25.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yavorska OO, Burgess S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol. 2017;46:1734–39.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Verbanck M, Chen C-Y, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:693–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Isaksen J, Egge A, Waterloo K, Romner B, Ingebrigtsen T. Risk factors for aneurysmal subarachnoid haemorrhage: the Tromsø study. J Neurol Neurosurg Psychiatry. 2002;73:185–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Noordzij M, Uiterwaal CS, Arends LR, Kok FJ, Grobbee DE, Geleijnse JM. Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens. 2005;23:921–8.

    Article  CAS  PubMed  Google Scholar 

  15. Bonita R. Cigarette smoking, hypertension and the risk of subarachnoid hemorrhage: a population-based case-control study. Stroke. 1986;17:831–35.

    Article  CAS  PubMed  Google Scholar 

  16. Inci S, Spetzler RF. Intracranial aneurysms and arterial hypertension: a review and hypothesis. Surg Neurol. 2000;53:530–40.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang Z, Wang M, Yuan S, Cai H, Zhu S-G, Liu X. Genetically predicted coffee consumption and risk of Alzheimer’s disease and stroke. J Alzheimer’s Dis. 2021;83:1815–23.

    Article  CAS  Google Scholar 

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We thank the International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm working group and UK Biobank. Summary information for intracranial aneurysms was obtained from the ISGC Cerebrovascular Disease Knowledge Portal.

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Authors and Affiliations



Z.Z. and X.L. designed the research, performed the statistical analysis, and drafted the paper. MW, SY, and SCL interpreted the data and made critical revisions of the paper.

Corresponding author

Correspondence to Xinfeng Liu.

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The authors declare no competing interests.

Ethical approval

Our analyses used publicly available genome-wide association study summary data. Each study included in this study had already obtained related ethical review board approvals, and all participants provided informed consent.

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Zhang, Z., Wang, M., Yuan, S. et al. Genetically predicted coffee and tea consumption and risk of intracranial aneurysm. Eur J Clin Nutr 77, 811–814 (2023).

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