Pathways among gene, metabolite, risk factor and disease identified among ARIC African Americans.

<p>Solid arrows between genes and metabolites indicate genome-wide significant effects (p<1.6×10⁻¹⁰). Arrows between metabolites and risk factors indicate significant linear associations after adjusting for age and gender (p<0.05). Arrows between metabolites and clinical endpoint indicate significant associations after adjusting for age, gender and other risk factors using Cox proportional hazards modeling (p<0.05). The dotted arrows between risk factors and clinical endpoints indicate well-established relationships. DBP indicates diastolic blood pressure and eGFR, estimated glomerular filtration rate.</p

A comparison of significant common variant-metabolite association among ARIC, KORA and TwinsUK studies.

<p>A comparison of significant common variant-metabolite association among ARIC, KORA and TwinsUK studies.</p

Nineteen significant GWAS loci for the human metabolome identified among African Americans in ARIC.

<p>Top SNP indicates the SNP with the lowest p-value; Ref Alleles, coded/non-coded alleles; MAF, minor allele frequency. All metabolites values were natural log-transformed prior to the analyses.</p

Genome-wide significant loci and human metabolic traits among African Americans in ARIC.

<p>Each hexagon shows the significant genetic locus (p<1.6×10⁻¹⁰) and the corresponding metabolite. The gene name listed in a hexagon is mapped by the sentinel SNP, and the closest gene is picked if the sentinel SNP was not located in a gene but is in linkage disequilibrium (r²≥0.8) with other SNPs in a nearby gene. Metabolites are grouped by super pathway, indicated in different colors. A red border line indicates that this gene-metabolite pair has been previously reported, and a gene name in red indicates the gene encodes an enzyme that catalyzes the reaction of the corresponding metabolite as a substrate or product. Rs number, risk allele, effect size and variance explained for the sentinel SNP are listed in parenthesis.</p

Additional file 1: of Metabolomic analysis of pathways related to rice grain chalkiness by a notched-belly mutant with high occurrence of white-belly grains

List of all metabolites identified and quantified by UPLC/MS/MS and GC/MS. (XLS 1325 kb

Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study

<div><p>Background</p><p>Atrial fibrillation (AF) is a common arrhythmia. Application of metabolomic approaches, which may identify novel pathways and biomarkers of disease risk, to a longitudinal epidemiologic study of AF has been limited.</p><p>Methods</p><p>We determined the prospective association of 118 serum metabolites identified through untargeted metabolomics profiling with the incidence of newly-diagnosed AF in 1919 African-American men and women from the Atherosclerosis Risk in Communities study without AF at baseline (1987–1989). Incident AF cases through 2011 were ascertained from study electrocardiograms, hospital discharge codes, and death certificates.</p><p>Results</p><p>During a median follow-up of 22 years, we identified 183 incident AF cases. In Cox proportional hazards models adjusted for age, sex, smoking, body mass index, systolic blood pressure, use of antihypertensive medication, diabetes, prevalent heart failure, prevalent coronary heart disease, and kidney function, two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were significantly associated with AF risk after correcting for multiple comparisons (p<0.0004). Multivariable-adjusted hazard ratios (95% confidence intervals) of AF were 1.22 (1.12–1.32) for glycolithocholate sulfate and 1.22 (1.10–1.35) for glycocholenate sulfate per 1-standard deviation higher levels. Associations were not appreciably different after additional adjustment for alcohol consumption or concentrations of circulating albumin and liver enzymes.</p><p>Conclusion</p><p>We found an association of higher levels of two bile acids with an increased risk of AF, pointing to a potential novel pathway in AF pathogenesis. Replication of results in independent studies is warranted.</p></div

Association of concentrations of glycolithocholate sulfate (A, left panel) and glycocholenate sulfate (B, right panel) with incidence of atrial fibrillation presented as hazard ratio (HR; solid line) and 95% confidence intervals (CI; shaded area).

<p>Results from Cox proportional hazards model with metabolites modeled using restricted cubic splines (knots at 5^th, 27.5^th, 50^th, 72.5^th, and 95^th percentiles), adjusted for age, sex, body mass index, smoking, diabetes, systolic blood pressure, use of antihypertensive medication, prevalent coronary heart disease, prevalent heart failure, and eGFR_CKD-EPI. Median value of the metabolite was considered the reference (HR = 1). The histograms represent the frequency distribution of both metabolites in the study sample. The red dots indicate the position of the knots used in the restricted cubic splines. Atherosclerosis Risk in Communities Study subsample, 1990–2011. eGFR_CKD-EPI: CKD-EPI creatinine-based estimated glomerular filtration rate.</p