Table 1 Ten significant gene-metabolite associations identified among African-Americans in ARIC.

Decanoylcarnitine and octanoylcarnitine were identified using the single-variant test, and the remains were identified using the gene-based burden test. Gene-related human pleiotropy was obtained through OMIM (Online Mendelian Inheritance in Man) (www.ncbi.nlm.nih.gov/omim) and the NHGRI GWAS catalog (www.genome.gov/gwastudies). NA, not applicable; LDL, low-density lipoprotein; MI, myocardial infarction; 5-HETE, 5-hydroxyicosatetraenoic acid; CHD, coronary heart disease; CVD, cardiovascular disease; MCAD, medium-chain acyl-CoA dehydrogenase.

MetabolitePathwayGenePβ (SE)cMACGene-related human
pleiotropy
Metabolite-related
human phenotypes
Replication
P
DecanoylcarnitineLipidCD362.7 × 10−7−0.19 (0.04)221Platelet glycoprotein IV
deficiency, CHD
MCAD deficiency (7)0.03
OctanoylcarnitineLipidCD363.9 × 10−8−0.20 (0.04)221Platelet glycoprotein IV
deficiency, CHD
MCAD deficiency (7)0.03
HistidineAmino acidHAL2.3 × 10−130.23 (0.03)26HistidinemiaRheumatoid arthritis (23),
CHD (24)
0.05
Methionine
sulfoxide
Amino acidC6orf251.3 × 10−8−0.45 (0.08)9Aging (25)NA
MannoseCarbohydrateTEX157.9 × 10−9−0.70 (0.12)10NA
CholesterolLipidPCSK95.4 × 10−9−0.21 (0.04)30LDL, CHD, MI, statin
response, familial
hypercholesterolemia
Atherosclerosis (26),
CVD (27)
0.0002
DeoxycarnitineLipidLRRC698.5 × 10−16−0.42 (0.05)170.6
HexadecanedioateLipidSLCO1B12.2 × 10−90.38 (0.06)67Hexadecanedioate,
tetradecanedioate,
octadecanedioate,
bilirubin,
hyperbilirubinemia,
statin-induced myopathy,
statin response
0.0001
5-HETELipidFAM198B4.5 × 10−9−0.38 (0.07)14NA
UrateNucleotideLRRC461.1 × 10−7−0.44 (0.08)10Gout (28), type 2
diabetes (29), CVD (30)
mortality (31)
NA