# Causal relationships involving brain imaging-derived phenotypes based on UKB imaging cohort: a review of Mendelian randomization studies

## TL;DR

This review summarizes how brain imaging data from the UK Biobank has been used to find causal links between lifestyle, diseases, and brain phenotypes using Mendelian randomization.

## Contribution

The paper systematically reviews MR studies using UKB imaging data to identify novel causal relationships between BIDPs and various factors.

## Key findings

- Causal links were found between lifestyle factors like alcohol consumption and brain imaging-derived phenotypes.
- Brain imaging phenotypes mediate the relationship between inactivity and major depressive disorder.
- BIDPs show causal relationships with diseases like Alzheimer's, stroke, and cardiovascular conditions.

## Abstract

The UK Biobank (UKB) has the largest adult brain imaging dataset, which encompasses over 40,000 participants. A significant number of Mendelian randomization (MR) studies based on UKB neuroimaging data have been published to validate potential causal relationships identified in observational studies. Relevant articles published before December 2023 were identified following the PRISMA protocol. Included studies (n = 34) revealed that there were causal relationships between various lifestyles, diseases, biomarkers, and brain image-derived phenotypes (BIDPs). In terms of lifestyle habits and environmental factors, there were causal relationships between alcohol consumption, tea intake, coffee consumption, smoking, educational attainment, and certain BIDPs. Additionally, some BIDPs could serve as mediators between leisure/physical inactivity and major depressive disorder. Regarding diseases, BIDPs have been found to have causal relationships not only with Alzheimer’s disease, stroke, psychiatric disorders, and migraine, but also with cardiovascular diseases, diabetes, poor oral health, osteoporosis, and ankle sprain. In addition, there were causal relationships between certain biological markers and BIDPs, such as blood pressure, LDL-C, IL-6, telomere length, and more.