Affiliations: [a]
Department of Neurology, Jinling Hospital, Medical School of Nanjing University, China
| [b]
Department of Neurology, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China
| [c]
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| [d]
Department of Neurology, Zhongshan City People’s Hospital, Zhongshan, Guangdong, China
| [e]
Department of Neurology, People’s Hospital of Longhua, Shenzhen, China
| [f]
Department of Neurology, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Zhanjiang, China
Correspondence:
[*]
Correspondence to: Xinfeng Liu and Shuang-Gen Zhu, Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. E-mails: [email protected] and [email protected]
Abstract: Background:Observational studies have reported that coffee consumption was associated with Alzheimer’s disease (AD) and stroke risk. However, the results are inconclusive. Objective:We aimed to evaluate whether genetically predicted coffee consumption is associated with AD and stroke using Mendelian randomization (MR) design. Methods:Summary-level data for AD (n = 54,162), ischemic stroke (n = 440,328), and intracerebral hemorrhage (ICH, n = 3,026) were adopted from publicly available databases. Summary-level data for coffee consumption were obtained from two genome-wide association studies, comprising up to 375,833 subjects. Results:Genetically predicted coffee consumption (cups/day) was associated with an increased risk of AD (OR = 1.26, 95%CI = 1.05–1.51). Moreover, genetically predicted 50%increase of coffee consumption was associated with an increased risk of ICH (OR: 2.27, 95%CI: 1.08–4.78) but a decreased risk of small vessel stroke (OR: 0.71, 95%CI: 0.51–0.996). Estimate for AD and ICH in FinnGen consortium is directionally consistent. Combined analysis of different databases further confirmed that genetically predicted coffee consumption was associated with an increased risk of AD and ICH. In the multivariable MR analysis, genetically predicted coffee consumption retained a stable effect with AD and ICH when adjusting for smoking (p < 0.05), while the association with AD attenuated when adjusting for alcohol use. Conclusion:Our results indicate that genetically predicted coffee consumption may be associated with an increased risk of AD and ICH. The underlying biological mechanisms warrant further study.
