P. Ler, K. Matta, M. J. Stein, L. Peruchet-Noray, D. Wu, Q. Gan, S. Beigrezaei, C. M. Lill, G. Masala, F. Ricceri, Y. T. van der Schouw, W. M. M. Verschuren, P. Vineis, A. M. Jimenez Zabala, R. Zamora-Ros, T. Y. Tong, K. Papier, M. J. Gunter, V. Viallon, P. Ferrari, J. Kim, H. Freisling
Plant-based diets may benefit planetary and human health. However, the molecular pathways linking plant-based diet quality to chronic diseases remain unclear. In 4,372 participants from the European Prospective Investigation into Cancer and Nutrition, we assessed 7,285 SomaScan-measured aptamers to identify circulating proteins associated with healthful (hPDI) and unhealthful (uPDI) plant-based dietary patterns using complementary statistical and machine-learning approaches. We then applied cis-pQTL Mendelian randomization (MR) and colocalization to prioritize diet-associated proteins with genetic evidence for associations with overall and site-specific cancers, type 2 diabetes (T2D), and cardiovascular disease (CVD). Among diet-associated proteins with MR evidence, 8 hPDI- and 12 uPDI-related protein-disease associations showed strong colocalization, including EGFR-breast cancer, MMP10-endometrial cancer, NCAN-T2D, and PCSK9-CVD. These findings identify candidate proteins that may link plant-based diet quality to chronic diseases and provide biological insights into the potential health benefits of healthful plant-based diets, which are increasingly relevant to public and planetary health.