Mendelian Randomization Identifies the Potential Causal Impact of Dietary Patterns on Circulating Blood Metabolites

Frontiers in Genetics

Nicola Pirastu¹  Hanna-Kristel Valge³  Krista Fischer⁴  Andres Metspalu⁵  Nele Taba⁵  James F. Wilson⁶  Tõnu Esko⁷ 

[1] Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom;Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia;Faculty of Medicine, University of Tartu, Tartu, Estonia;Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia;Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia;MRC Human Genetics Unit, Western General Hospital, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom;Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States;

关键词: dietary intake;    nutrition;    metabolomics;    two-sample mendelian randomization;    dietary patterns;    lipid metabolism;   

DOI  :  10.3389/fgene.2021.738265

来源: DOAJ

【 摘 要 】

Nutrition plays an important role in the development and progress of several health conditions, but the exact mechanism is often still unclear. Blood metabolites are likely candidates to be mediating these relationships, as their levels are strongly dependent on the frequency of consumption of several foods/drinks. Understanding the causal effect of food on metabolites is thus of extreme importance. To establish these effects, we utilized two-sample Mendelian randomization using the genetic variants associated with dietary traits as instrumental variables. The estimates of single-nucleotide polymorphisms’ effects on exposures were obtained from a recent genome-wide association study (GWAS) of 25 individual and 15 principal-component dietary traits, whereas the ones for outcomes were obtained from a GWAS of 123 blood metabolites measured by nuclear magnetic resonance spectroscopy. We identified 413 potentially causal links between food and metabolites, replicating previous findings, such as the association between increased oily fish consumption and higher DHA, and highlighting several novel associations. Most of the associations were related to very-low-density, intermediate-density (IDL), and low-density lipoproteins (LDL). For example, we found that constituents of IDL particles and large LDL particles were raised by coffee and alcohol while lowered by an overall healthier diet and fruit consumption. Our findings provide a strong base of evidence for planning future RCTs aimed at understanding the role of diet in determining blood metabolite levels.

【 授权许可】

Unknown