Nov 12, 2018

A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context

BioRxiv : the Preprint Server for Biology
Apolline GalloisHugues Aschard

Abstract

Genetic studies of metabolites have identified thousands of variants many of which are associated with downstream metabolic and obesogenic disorders. However, these studies have relied on univariate analyses, reducing power and limiting context specific understanding. Here we aim to provide an integrated perspective of the genetic basis of metabolites by leveraging the Finnish Metabolic Syndrome In Men (METSIM) cohort, a unique genetic resource which contains metabolic measurements across distinct timepoints as well as detailed information on statin usage. We increase effective sample size by an average of two-fold by applying the Covariates for Multi-phenotype Studies (CMS) approach, identifying 588 significant SNP-metabolite associations, including 248 novel associations. We further show that many of these SNPs are master metabolic regulators, balancing the relative proportion of dozens of metabolite levels. We then identify the first associations to changes in metabolic levels across time as well as evidence of genetic interaction with statin use. Finally, we show an overall decrease in genetic control of metabolic processes with age.

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Mentioned in this Paper

Metabolic Process, Cellular
Study
Univariate Analysis
Classification
Finnish
Genetic Pleiotropy
Equilibrium
Metabolic Syndrome X
Regulation of Metabolic Process
Multicenter Study

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