Metabolomic patterns and alcohol consumption in African Americans in the Atherosclerosis Risk in Communities Study.
BACKGROUND
Effects of alcohol consumption on health and disease are complex and involve a number of cellular and metabolic processes.


OBJECTIVE
We examined the association between alcohol consumption habits and metabolomic profiles.


METHODS
We conducted a cross-sectional study to explore the association of alcohol consumption habits measured by using a questionnaire with serum metabolites measured by using untargeted mass spectrometry in 1977 African Americans from the Jackson field center in the Atherosclerosis Risk in Communities Study. The whole sample was split into a discovery set (n = 1500) and a replication set (n = 477). Alcohol consumption habits were treated as an ordinal variable, with nondrinkers as the reference group and quartiles of current drinkers as ordinal groups with higher values. For each metabolite, a linear regression was conducted to estimate its relation with alcohol consumption habits separately in both sets. A modified Bonferroni procedure was used in the discovery set to adjust the significance threshold (P < 1.9 × 10⁻⁴).


RESULTS
In 356 named metabolites, 39 metabolites were significantly associated with alcohol consumption habits in both discovery and replication sets. In general, alcohol consumption was associated with higher levels of most metabolites such as those in amino acid and lipid pathways and with lower levels of γ-glutamyl dipeptides. Three pathways, 2-hydroxybutyrate-related metabolites, γ-glutamyl dipeptides, and lysophosphatidylcholines, which are considered to be involved in inflammation and oxidation, were associated with incident cardiovascular diseases.


CONCLUSIONS
To our knowledge, this is the largest metabolomic study thus far conducted in nonwhites. Metabolomic biomarkers of alcohol consumption were identified and replicated. The results lend new insight into potential mediating effects between alcohol consumption and future health and disease.
From the Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX (YZ, BY, JAN, and EB); Metabolon Inc, Durham, NC (DA); the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (LMS); and the Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (EB).
Yan
Y
Zheng
From the Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX (YZ, BY, JAN, and EB); Metabolon Inc, Durham, NC (DA); the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (LMS); and the Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (EB).
Bing
B
Yu
From the Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX (YZ, BY, JAN, and EB); Metabolon Inc, Durham, NC (DA); the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (LMS); and the Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (EB).
Danny
D
Alexander
From the Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX (YZ, BY, JAN, and EB); Metabolon Inc, Durham, NC (DA); the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (LMS); and the Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (EB).
Lyn M
LM
Steffen
From the Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX (YZ, BY, JAN, and EB); Metabolon Inc, Durham, NC (DA); the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (LMS); and the Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (EB).
Jennifer A
JA
Nettleton
From the Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX (YZ, BY, JAN, and EB); Metabolon Inc, Durham, NC (DA); the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (LMS); and the Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (EB).
Eric
E
Boerwinkle
D001741:Black or African American; D000428:Alcohol Drinking / Q000009:adverse effects / Q000097:blood / Q000208:ethnology / Q000378:metabolism*; D050197:Atherosclerosis / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D015203:Reproducibility of Results; D012307:Risk Factors; D014481:United States; D015854:Up-Regulation
D015415:Biomarkers