Genetic determinants of metabolism in health and disease: from biochemical genetics to genome-wide associations

Robinette, Steven L.; Holmes, Elaine; Nicholson, Jeremy K.; Dumas, Marc

doi:10.1186/gm329

Cited by 31 publications

(16 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The parallel development of biobanking and high-throughput sequencing, genotyping and phenotyping technologies has enabled a new generation of successful molecular epidemiology studies, such as genome-wide association studies (GWAS) [1], metabolome-wide association studies (MWAS) [2,3] and even metabolomics GWASes [4,5,6]. It currently provides a wide range of new opportunities for the development of biomarkers of medical interest with current applications in toxicology [7], cancer [8,9,10], cardiovascular disease [11,12], prediction of treatment outcomes [13,14,15] or “pharmacometabonomics” [16,17], and more recently metabolic modelling of the patient journey in a clinical environment [18,19].…”

Section: Introductionmentioning

confidence: 99%

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

Jobard

Trédan

Postoly

et al. 2016

IJMS

View full text Add to dashboard Cite

The recent thriving development of biobanks and associated high-throughput phenotyping studies requires the elaboration of large-scale approaches for monitoring biological sample quality and compliance with standard protocols. We present a metabolomic investigation of human blood samples that delineates pitfalls and guidelines for the collection, storage and handling procedures for serum and plasma. A series of eight pre-processing technical parameters is systematically investigated along variable ranges commonly encountered across clinical studies. While metabolic fingerprints, as assessed by nuclear magnetic resonance, are not significantly affected by altered centrifugation parameters or delays between sample pre-processing (blood centrifugation) and storage, our metabolomic investigation highlights that both the delay and storage temperature between blood draw and centrifugation are the primary parameters impacting serum and plasma metabolic profiles. Storing the blood drawn at 4 °C is shown to be a reliable routine to confine variability associated with idle time prior to sample pre-processing. Based on their fine sensitivity to pre-analytical parameters and protocol variations, metabolic fingerprints could be exploited as valuable ways to determine compliance with standard procedures and quality assessment of blood samples within large multi-omic clinical and translational cohort studies.

show abstract

Section: Introductionmentioning

confidence: 99%

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

Jobard

Trédan

Postoly

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…hagsc.org/hgdp/), 1000 Genomes Projects (Durbin et al 2010), and every published whole-genome sequence [references in (Olson 2012)] demonstrated that individuals are genetically unique. Metabolomic, proteomic, and clinical data also demonstrate biochemical individuality (Williams 1956;Robinette et al 2012). Adj p value = corrected for multiple comparisons…”

Section: Experimental Design and Main Resultsmentioning

confidence: 99%

Methylation potential associated with diet, genotype, protein, and metabolite levels in the Delta Obesity Vitamin Study

et al. 2014

View full text Add to dashboard Cite

Micronutrient research typically focuses on analyzing the effects of single or a few nutrients on health by analyzing a limited number of biomarkers. The observational study described here analyzed micronutrients, plasma proteins, dietary intakes, and genotype using a systems approach. Participants attended a community-based summer day program for 6-14 year old in 2 years. Genetic makeup, blood metabolite and protein levels, and dietary differences were measured in each individual. Twenty-four-hour dietary intakes, eight micronutrients (vitamins A, D, E, thiamin, folic acid, riboflavin, pyridoxal, and pyridoxine) and 3 one-carbon metabolites [homocysteine (Hcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH)], and 1,129 plasma proteins were analyzed as a function of diet at metabolite level, plasma protein level, age, and sex. Cluster analysis identified two groups differing in SAM/SAH and differing in dietary intake patterns indicating that SAM/SAH was a potential marker of nutritional status. The approach used to analyze genetic association with the SAM/SAH metabolites is called middle-out: SNPs in 275 genes involved in the one-carbon pathway (folate, pyridoxal/pyridoxine, thiamin) or were correlated with SAM/SAH (vitamin A, E, Hcy) were analyzed instead of the entire 1M SNP data set. This procedure identified 46 SNPs in 25 genes associated with SAM/SAH demonstrating a genetic contribution to the methylation potential. Individual plasma metabolites correlated with 99 plasma proteins. Fourteen proteins correlated with body mass index, 49 with group age, and 30 with sex. The analytical strategy described here identified subgroups for targeted nutritional interventions.

show abstract

“…Thousands of GWA studies have been published associating one or more single nucleotide variants to ~800 phenotypes that include disease [106], diet intake [94], metabolism [8, 81], anthropometry [106], pharmacogenomics [17, 70], and brain-related disorders [56]. Over 15,000 trait–SNP associations at p value ≤5.0 × 10 −8 have been amassed as of 2013 ([106] and https://www.ebi.ac.uk/gwas/).…”

Section: Guidelines Standards and Reproducibility Of Scientific Datmentioning

confidence: 99%

Propelling the paradigm shift from reductionism to systems nutrition

Kaput

Perozzi²,

Radonjić³

et al. 2017

Genes Nutr

View full text Add to dashboard Cite

The complex physiology of living organisms represents a challenge for mechanistic understanding of the action of dietary bioactives in the human body and of their possible role in health and disease. Animal, cell, and microbial models have been extensively used to address questions that could not be pursued experimentally in humans, posing an additional level of complexity in translation of the results to healthy and diseased metabolism. The past few decades have witnessed a surge in development of increasingly sensitive molecular techniques and bioinformatic tools for storing, managing, and analyzing increasingly large datasets. Application of such powerful means to molecular nutrition research led to a major leap in study designs and experimental approaches yielding experimental data connecting dietary components to human health. Scientific journals bear major responsibilities in the advancement of science. As primary actors of dissemination to the scientific community, journals can impose rigid criteria for publishing only sound, reliable, and reproducible data. Journal policies are meant to guide potential authors to adopt the most updated standardization guidelines and shared best practices. Such policies evolve in parallel with the evolution of novel approaches and emerging challenges and therefore require constant updating. We highlight in this manuscript the major scientific issues that led to formulating new, updated journal policies for Genes & Nutrition, a journal which targets the growing field of nutritional systems biology interfacing personalized nutrition and preventive medicine, with the ultimate goal of promoting health and preventing or treating disease. We focus here on relevant issues requiring standardization in nutrition research. We also introduce new sections on human genetic variation and nutritional bioinformatics which follow the evolution of nutritional science into the twenty-first century.

show abstract

Genetic determinants of metabolism in health and disease: from biochemical genetics to genome-wide associations

Cited by 31 publications

References 102 publications

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

Methylation potential associated with diet, genotype, protein, and metabolite levels in the Delta Obesity Vitamin Study

Propelling the paradigm shift from reductionism to systems nutrition

Contact Info

Product

Resources

About