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Improving Visualization and Interpretation of Metabolome-Wide Association Studies: An Application in a Population-Based Cohort Using Untargeted 1H NMR Metabolic Profiling
- Source :
- Journal of Proteome Research
- Publication Year :
- 2017
- Publisher :
- American Chemical Society, 2017.
-
Abstract
- 1H NMR spectroscopy of biofluids generates reproducible data allowing detection and quantification of small molecules in large population cohorts. Statistical models to analyze such data are now well-established, and the use of univariate metabolome wide association studies (MWAS) investigating the spectral features separately has emerged as a computationally efficient and interpretable alternative to multivariate models. The MWAS rely on the accurate estimation of a metabolome wide significance level (MWSL) to be applied to control the family wise error rate. Subsequent interpretation requires efficient visualization and formal feature annotation, which, in-turn, call for efficient prioritization of spectral variables of interest. Using human serum 1H NMR spectroscopic profiles from 3948 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), we have performed a series of MWAS for serum levels of glucose. We first propose an extension of the conventional MWSL that yields stable estimates of the MWSL across the different model parameterizations and distributional features of the outcome. We propose both efficient visualization methods and a strategy based on subsampling and internal validation to prioritize the associations. Our work proposes and illustrates practical and scalable solutions to facilitate the implementation of the MWAS approach and improve interpretation in large cohort studies.
- Subjects :
- Adult
Aged, 80 and over
Blood Glucose
Male
Proton Magnetic Resonance Spectroscopy
metabolic profiling
metabolome wide association study
multiple testing correction
Middle Aged
Atherosclerosis
molecular epidemiology
Article
high-throughput analysis
Cohort Studies
full resolution 1H NMR
significance level
Metabolome
Humans
Metabolomics
MESA
Female
results visualization and prioritization
Aged
Subjects
Details
- Language :
- English
- ISSN :
- 15353907 and 15353893
- Volume :
- 16
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of Proteome Research
- Accession number :
- edsair.pmid..........a8dd46fa2d337ad37b4501e948d0c6d1