Abstract
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.
Highlights
Nutrition plays an important role in the development and progress of several diseases, such as obesity (Popkin, 2001), type II diabetes (T2D) (Schwingshackl et al, 2017), cardiovascular diseases (CVD) (Boeing et al, 2012; Dilis et al, 2012; Schaefer, 2002), and cancer (Key et al, 2004; Johnson and Lund, 2007)
In order to distinguish which variables are likely directly associated with the food of interest, we have previously developed a method called Corrected to Uncorrected ratio filtering (CUR), which is based on the idea that if the single-nucleotide polymorphisms (SNPs) is directly associated with food preferences, its effect should not change when adjusted for education status or health conditions (Pirastu et al, 2019)
After correcting for multiple testing by using the false discovery rate (FDR
Summary
Nutrition plays an important role in the development and progress of several diseases, such as obesity (Popkin, 2001), type II diabetes (T2D) (Schwingshackl et al, 2017), cardiovascular diseases (CVD) (Boeing et al, 2012; Dilis et al, 2012; Schaefer, 2002), and cancer (Key et al, 2004; Johnson and Lund, 2007). A metabolite can be an objective biomarker of dietary intake while not acting as an intermediate in diet–disease relationships. The main focus of this paper is investigating the diet–metabolite associations where metabolites may act as intermediates in diet–disease relationships
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