In a recent study published in the European Journal of Clinical Nutrition, researchers use Mendelian randomization (MR) techniques to establish a causal link between coffee consumption and reduction in migraine risk.
Study: Causal relationship between coffee intake and neurological diseases: a Mendelian randomization study. Image Credit: Farknot Architect / Shutterstock.com
Neurological diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), migraines, multiple sclerosis (MS), Parkinson’s disease (PD), and stroke are leading causes of death and disability worldwide. The effects of these diseases on the nervous system impair cognition and cause pain, headaches, seizures, and movement disorders.
In 2016 alone, neurological diseases were responsible for nearly 10% of deaths and 16% of disability-adjusted life-years in the world. Research on what causes these diseases, as well as how to prevent them, is urgently required.
Coffee is one of the most commonly consumed beverages in the world, which has led many scientists to evaluate its possible impacts on human health. However, these studies were primarily observational, thus making it difficult for researchers to remove the effects of bias and possible reverse causality.
About the study
MR offers a method of assessing the causal effect of a risk factor and the disease which, in the current study, would be coffee consumption and neurological diseases, respectively. MR utilizes genetic data that are associated with the risk factor but not the diseases themselves and uses this information as instrumental variables (IVs). In the current study, researchers identified single-nucleotide polymorphisms (SNPs) that are known to influence coffee consumption as the IVs.
The use of IVs rests on three key assumptions. First, the instruments should have a strong association with the exposure. Second, IVs should not have any association with possible confounding factors, which also affect the risk of the disease. Additionally, the only effect that the instruments should have on the disease should be through their effect on the exposure.
Using the genome-wide association study (GWAS) from the United Kingdom Biobank, researchers identified 40 SNPs, each independent of the other, based on more than 400,000 people of European descent. SNPs were validated so that their association with coffee intake had a genome-wide significance threshold of less than 5x10-8. F statistics of more than 10 were also used to reduce the effect of biases.
Several other datasets including the International Genomics of Alzheimer’s Project, International Parkinson’s Disease Genomics Consortium, and International Multiple Sclerosis Genetics Consortium were also utilized to obtain the necessary data on neurological diseases.
An inverse variance weight (IVW) meta-analysis was conducted. MR pleiotropy residual sum and outlier tests were used to remove potentially pleiotropic instruments. At each stage of analysis, outlier IVs were removed to strengthen the results.
The 40 SNPs selected as IVs had F statistics between 16 and 359, thus indicating that they are strong instruments. According to the IVW analysis, coffee consumption reduced the risk of migraine and migraine with aura. These findings were validated through the use of a ‘leave-one-out’ analysis, in which no single IV was responsible for the result.
No association between coffee consumption and migraine without aura was observed, nor was any evidence of horizontal pleiotropy. Furthermore, no associations between coffee consumption and any of the other neurological diseases or any of their subtypes were observed. The heterogeneity in the results did not affect these conclusions.
The study findings indicate robust causal associations between coffee consumption and reduced migraine risk; however, no association with other major neurological diseases was identified. These findings contribute to a vast body of literature that assesses the effect of coffee on human health but are distinct in their use of IVs and genetic data to mitigate the effect of biases and various confounding factors.
Although the results are convincing, the researchers highlight certain limitations. For example, all sources of potential directional pleiotropy were not necessarily excluded, which is a common challenge in MR studies. Additionally, the researchers did not assess how coffee was consumed, which indicates that a vital dietary component remains to be assessed.
Another major limitation is that the study focuses only on people of European descent. Thus, it is imperative to include South Asians, East Asians, and individuals of other ethnicities in future studies.
- Zhang, J., Liu, Y., Cao, X., et al. (2023). Causal relationship between coffee intake and neurological diseases: a Mendelian randomization study. European Journal of Clinical Nutrition. doi:10.1038/s41430-023-01355-y