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Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study.

ABSTRACT: Both the prevalence and incidence of heart failure (HF) are increasing, especially among African Americans, but no large-scale, genome-wide association study (GWAS) of HF-related metabolites has been reported. We sought to identify novel genetic variants that are associated with metabolites previously reported to relate to HF incidence. GWASs of three metabolites identified previously as risk factors for incident HF (pyroglutamine, dihydroxy docosatrienoic acid, and X-11787, being either hydroxy-leucine or hydroxy-isoleucine) were performed in 1,260 African Americans free of HF at the baseline examination of the Atherosclerosis Risk in Communities (ARIC) study. A significant association on chromosome 5q33 (rs10463316, MAF = 0.358, P-value = 1.92 × 10(-10) ) was identified for pyroglutamine. One region on chromosome 2p13 contained a nonsynonymous substitution in N-acetyltransferase 8 (NAT8) was associated with X-11787 (rs13538, MAF = 0.481, P-value = 1.71 × 10(-23) ). The smallest P-value for dihydroxy docosatrienoic acid was rs4006531 on chromosome 8q24 (MAF = 0.400, P-value = 6.98 × 10(-7) ). None of the above SNPs were individually associated with incident HF, but a genetic risk score (GRS) created by summing the most significant risk alleles from each metabolite detected 11% greater risk of HF per allele. In summary, we identified three loci associated with previously reported HF-related metabolites. Further use of metabolomics technology will facilitate replication of these findings in independent samples.

SUBMITTER: Yu B

PROVIDER: S-EPMC4079107 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study.

Yu Bing B Zheng Yan Y Alexander Danny D Manolio Teri A TA Alonso Alvaro A Nettleton Jennifer A JA Boerwinkle Eric E

Genetic epidemiology 20130811 8

Both the prevalence and incidence of heart failure (HF) are increasing, especially among African Americans, but no large-scale, genome-wide association study (GWAS) of HF-related metabolites has been reported. We sought to identify novel genetic variants that are associated with metabolites previously reported to relate to HF incidence. GWASs of three metabolites identified previously as risk factors for incident HF (pyroglutamine, dihydroxy docosatrienoic acid, and X-11787, being either hydroxy ...[more]

PMID: 23934736

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Project description:BACKGROUND:Previous studies suggest that heart failure (HF) is an independent risk factor for cognitive decline. A better understanding of the relationship between HF, cognitive status, and cognitive decline in a community-based sample may help clinicians understand disease risk. OBJECTIVE:To examine whether persons with HF have a higher prevalence of cognitive impairment and whether persons developing HF have more rapid cognitive decline. DESIGN:This observational cohort study of American adults in the Atherosclerosis Risk in Communities (ARIC) study has two components: cross-sectional analysis examining the association between prevalent HF and cognition using multinomial logistic regression, and change over time analysis detailing the association between incident HF and change in cognition over 15 years. PARTICIPANTS:Among visit 5 (2011-2013) participants (median age 75 years), 6495 had neurocognitive information available for cross-sectional analysis. Change over time analysis examined the 5414 participants who had cognitive scores and no prevalent HF at visit 4 (1996-1998). MEASUREMENTS:The primary outcome was cognitive status, classified as normal, mild cognitive impairment [MCI], and dementia on the basis of standardized cognitive tests (delayed word recall, word fluency, and digit symbol substitution). Cognitive change was examined over a 15-year period. Control variables included socio-demographic, vascular, and smoking/drinking measures. RESULTS:At visit 5, participants with HF had a higher prevalence of dementia (adjusted relative risk ratio [RRR] = 1.60 [95% CI 1.13, 2.25]) and MCI (RRR = 1.36 [1.12, 1.64]) than those without HF. A decline in cognition between visits 4 and 5 was - 0.07 standard deviation units [- 0.13, - 0.01] greater among persons who developed HF compared to those who did not. Results did not differ by ejection fraction. CONCLUSION:HF is associated with neurocognitive dysfunction and decline independent of other co-morbid conditions. Further study is needed to determine the underlying pathophysiology.

Dataset Information

Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study.

Publications

Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study.

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