Metabolite Genome-Wide Association in Hispanics with Obesity Reveals Genetic Risk and Interactions with Dietary...

Obesity is a leading cause of type 2 diabetes (T2D), with particularly high prevalence in Hispanic populations residing in the USA. However, how genetic variation influences obesity-related blood metabolite levels which, in turn, contribute to T2D progression, is not well understood. Our goal was to identify and understand genetic and dietary connections between obesity and T2D in a Hispanic cohort of older adults.

We conducted a genome-wide association study on 13 specific metabolites previously associated with T2D and characteristic of individuals with abdominal obesity within the Boston Puerto Rican Health Study cohort. We further examined associations of identified metabolite quantitative trait loci (mQTLs) and their interactions with targeted dietary factors on T2D prevalence and related traits. We used gene set and pathway analysis with protein-protein interaction networks to explore the molecular mechanisms underlying the metabolic connections between obesity and T2D.

We identified 30 single-nucleotide polymorphisms (SNPs) acting as mQTLs for these 13 metabolites. These mQTLs were located within 19 gene regions, associated with processes such as linoleic acid metabolism, alpha-linolenic acid metabolism, and glycerophospholipid biosynthesis. Although no mQTLs were directly associated with T2D or related traits, 12 demonstrated interactions with certain food groups that affect T2D risk. Moreover, gene set and pathway analysis with protein-protein interaction networks indicated that alpha-linolenic acid metabolism, lipid metabolism, and glycerophospholipid biosynthesis and metabolism among other pathways are potential connections between T2D and obesity.

This study identifies biochemical relationships between genetic susceptibility and dietary influences, contributing to our understanding of T2D progression in Hispanic people with obesity.