TY - JOUR
T1 - Associations between the serum metabolome and all-cause mortality among African Americans in the Atherosclerosis Risk in Communities (ARIC) Study
AU - Yu, Bing
AU - Heiss, Gerardo
AU - Alexander, Danny
AU - Grams, Morgan E.
AU - Boerwinkle, Eric
N1 - Publisher Copyright:
© 2016 The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Early and accurate identification of people at high risk of premature death may assist in the targeting of preventive therapies in order to improve overall health. To identify novel biomarkers for all-cause mortality, we performed untargeted metabolomics in the Atherosclerosis Risk in Communities (ARIC) Study. We included 1,887 eligible ARIC African Americans, and 671 deaths occurred during a median follow-up period of 22.5 years (1987-2011). Chromatography and mass spectroscopy identified and quantitated 204 serum metabolites, and Cox proportional hazards models were used to analyze the longitudinal associations with all-cause and cardiovascular mortality. Nine metabolites, including cotinine, mannose, glycocholate, pregnendiol disulfate, α-hydroxyisovalerate, N-acetylalanine, andro-steroid monosulfate 2, uridine, and γ-glutamyl-leucine, showed independent associations with all-cause mortality, with an average risk change of 18% per standard-deviation increase in metabolite level (P < 1.23 × 10-4). A metabolite risk score, created on the basis of the weighted levels of the identified metabolites, improved the predictive ability of all-cause mortality over traditional risk factors (bias-corrected Harrell's C statistic 0.752 vs. 0.730). Mannose and glycocholate were associated with cardiovascular mortality (P < 1.23 × 10-4), but predictive ability was not improved beyond the traditional risk factors. This metabolomic analysis revealed potential novel biomarkers for all-cause mortality beyond the traditional risk factors.
AB - Early and accurate identification of people at high risk of premature death may assist in the targeting of preventive therapies in order to improve overall health. To identify novel biomarkers for all-cause mortality, we performed untargeted metabolomics in the Atherosclerosis Risk in Communities (ARIC) Study. We included 1,887 eligible ARIC African Americans, and 671 deaths occurred during a median follow-up period of 22.5 years (1987-2011). Chromatography and mass spectroscopy identified and quantitated 204 serum metabolites, and Cox proportional hazards models were used to analyze the longitudinal associations with all-cause and cardiovascular mortality. Nine metabolites, including cotinine, mannose, glycocholate, pregnendiol disulfate, α-hydroxyisovalerate, N-acetylalanine, andro-steroid monosulfate 2, uridine, and γ-glutamyl-leucine, showed independent associations with all-cause mortality, with an average risk change of 18% per standard-deviation increase in metabolite level (P < 1.23 × 10-4). A metabolite risk score, created on the basis of the weighted levels of the identified metabolites, improved the predictive ability of all-cause mortality over traditional risk factors (bias-corrected Harrell's C statistic 0.752 vs. 0.730). Mannose and glycocholate were associated with cardiovascular mortality (P < 1.23 × 10-4), but predictive ability was not improved beyond the traditional risk factors. This metabolomic analysis revealed potential novel biomarkers for all-cause mortality beyond the traditional risk factors.
KW - all-cause mortality
KW - cardiovascular mortality
KW - metabolomics
KW - risk factors
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U2 - 10.1093/aje/kwv213
DO - 10.1093/aje/kwv213
M3 - Article
C2 - 26956554
AN - SCOPUS:84964658648
SN - 0002-9262
VL - 183
SP - 650
EP - 656
JO - American journal of epidemiology
JF - American journal of epidemiology
IS - 7
ER -