ABSTRACT Dietary patterns (DPs) integrate complex eating behaviors and provide stronger insights into health than analyses of single nutrients. However, most studies have examined only a limited range of outcomes, and the biological mechanisms underlying DPs remain poorly defined. Using a robust data‐driven approach, we derived three major DPs from dietary recall data and evaluated their associations with > 1000 diseases and biomarkers. Mediation analyses investigated metabolic intermediates, and genome‐wide association studies (GWAS) identified genetic loci shaping DPs. DP1 represented a plant‐forward, nutrient‐dense profile; DP2 was meat‐and‐vegetables oriented; and DP3 was characterized by energy‐dense snack intake. In phenome‐wide association analyses, DP1 was broadly protective, inversely associated with over 50 diseases, whereas DP3 was detrimental, linked to increased risk across more than 60 outcomes. DP2 showed limited associations. Mediation analyses indicated that the benefits of DP1 were partly attributable to higher circulating polyunsaturated fatty acids, while the harms of DP3 were mediated through lower high‐density lipoprotein levels. GWAS revealed distinct genetic underpinnings, linking DP1 to APOE , APOC1 , and NEGR1 , and DP3 to the MAPT locus. Together, these findings provide a comprehensive characterization of DPs, reveal metabolic and genetic pathways underlying diet‐disease relationships, and highlight opportunities for advancing personalized nutrition and disease prevention.
Shi et al. (Wed,) studied this question.