Increased Brain Volume from Higher Cereal and Lower Coffee Intake: Shared Genetic Determinants and Impacts on Cognition and Metabolism

Background: It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part. Methods: We used cross-sectional observational data from UK Biobank. Only white British individuals free of Alzheimer's or dementia diseases were included in the study. We conducted linear regression analysis and mediation models to examine the association between diets, gerey matter volume, genetic variants, lifestyle, and metabolic measures. We tested the association between the GMV-association patterns of the cereal/coffee intake, the GMV-association patterns of cognitive functions and the gene-expression patterns. Findings: Overall, 336517 participants were included in our analysis. We discovered anti-correlated brain-wide grey matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anti-correlated genetic constructs. These genetic factors may further affect people’s lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions. Interpretation: Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, BMI and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs. Funding Statement: This work received support from the following sources: the National Key Research and Development Program of China (2018YFC1312900 and 2019YFA0709502), the National Natural Science Foundation of China (91630314 and 81801773), the 111 Project (B18015), The Key Project of Shanghai Science &Technology Innovation Plan(16JC1420402), the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01) and Zhangjiang Lab. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All participants provided written informed consent to UK Biobank. The UK Biobank study received ethical approval from the NHS National Research Ethics Service North West (reference number: 16/NW/0274). Data access permission was granted under UKB application 19542 (PI Jianfeng Feng).