Triangulating evidence from longitudinal and Mendelian randomization studies of metabolomic biomarkers for type 2 diabetes.

Details

Ressource 1Download: 33737653.pdf (928.77 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_31003871533C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Triangulating evidence from longitudinal and Mendelian randomization studies of metabolomic biomarkers for type 2 diabetes.
Journal
Scientific reports
Author(s)
Porcu E., Gilardi F., Darrous L., Yengo L., Bararpour N., Gasser M., Marques-Vidal P., Froguel P., Waeber G., Thomas A., Kutalik Z.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
18/03/2021
Peer-reviewed
Oui
Volume
11
Number
1
Pages
6197
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The number of people affected by Type 2 diabetes mellitus (T2DM) is close to half a billion and is on a sharp rise, representing a major and growing public health burden. Given its mild initial symptoms, T2DM is often diagnosed several years after its onset, leaving half of diabetic individuals undiagnosed. While several classical clinical and genetic biomarkers have been identified, improving early diagnosis by exploring other kinds of omics data remains crucial. In this study, we have combined longitudinal data from two population-based cohorts CoLaus and DESIR (comprising in total 493 incident cases vs. 1360 controls) to identify new or confirm previously implicated metabolomic biomarkers predicting T2DM incidence more than 5 years ahead of clinical diagnosis. Our longitudinal data have shown robust evidence for valine, leucine, carnitine and glutamic acid being predictive of future conversion to T2DM. We confirmed the causality of such association for leucine by 2-sample Mendelian randomisation (MR) based on independent data. Our MR approach further identified new metabolites potentially playing a causal role on T2D, including betaine, lysine and mannose. Interestingly, for valine and leucine a strong reverse causal effect was detected, indicating that the genetic predisposition to T2DM may trigger early changes of these metabolites, which appear well-before any clinical symptoms. In addition, our study revealed a reverse causal effect of metabolites such as glutamic acid and alanine. Collectively, these findings indicate that molecular traits linked to the genetic basis of T2DM may be particularly promising early biomarkers.
Keywords
Multidisciplinary
Pubmed
Open Access
Yes
Create date
22/03/2021 9:27
Last modification date
27/03/2021 7:32
Usage data