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. Author manuscript; available in PMC: 2022 Aug 1.
Published in final edited form as: Ann Rheum Dis. 2021 Mar 22;80(8):989–996. doi: 10.1136/annrheumdis-2020-219682

Table 4.

Changes in Metabolites per Year in 229 Pre-Seropositive Rheumatoid Arthritis (RA) Cases and 193 Controls for Metabolites with Differential Trajectories over Time, adjusted for smoking

Time Pre-RA Cases vs. Controls Time*Pre-RA Status
Super Class Sub-Pathway Name HMDB β T p β G p β Intx p q
Steroids Androsterone Glucuronides ±androsterone glucuronide HMDB0002829 0.025 0.015 −0.411 1.12E-06 −0.095 3.44E-06 0.001*
Pregnenolone Steroids ±17-hydroxypregnenolone sulfate HMDB0000416 −0.032 0.029 −0.442 3.60E-06 −0.112 1.91E-04 0.025*
pregnenolone sulfate HMDB0000774 0.014 0.264 −0.422 3.07E-06 −0.089 4.46E-04 0.039*
Lipids Long Chain Fatty Acids hydroxymyristate HMDB0002261 −0.021 0.192 −0.272 0.003 −0.075 0.018 0.117
Fatty Acid Metabolism (Acyl Carnitine) C2 carnitine HMDB0000201 0.171 4.03E-33 −0.185 0.014 −0.067 0.012 0.105
C9 carnitine HMDB0013288 0.014 0.321 −0.267 0.003 −0.079 0.005 0.074
Glycerophospholipids C40:7 phosphatidylethanolamine plasmalogen HMDB0011394 0.104 2.78E-11 −0.415 7.20E-06 −0.056 0.066 0.242
Amino Acids Leucine, Isoleucine and Valine Metabolism N-acetylleucine HMDB0011756 −0.037 0.026 0.231 0.020 0.101 0.002 0.066
Tyrosine Metabolism tyramine HMDB0000306 −0.044 0.001 0.901 3.39E-20 0.080 0.003 0.070
Xenobiotics Food/Plant Components levulinate HMDB0000720 0.147 9.40E-18 −0.507 6.10E-08 −0.103 0.002 0.063
Caffeine/Xanthine Metabolites 1,7-dimethyluric acid HMDB0011103 0.058 2.55E-04 −0.238 0.001 −0.101 0.002 0.061
theophylline HMDB0001889 0.051 0.001 −0.243 0.001 −0.104 9.48E-04 0.053
caffeine HMDB0001847 0.058 2.37E-04 −0.200 0.037 −0.081 0.010 0.100
Drugs naproxen HMDB0001923 0.017 0.360 0.384 1.15E-04 0.112 0.003 0.068

p: p-value; q: false discovery rate adjusted q-statistic for likelihood ratio test of the time * group effect

C: Carbon,

*

p< 0.05 and FDR q < 0.05

βT: change in relative metabolite concentration per year in controls; βG: difference in relative metabolite concentration in pre-RA cases vs. controls; βIntx: change in βT per year given pre-RA case status, i.e. difference in rate of change in relative metabolite concentrations per year in pre-RA cases vs. controls

**

p< 0.05 and FDR q < 0.05 after adjustment for smoking

±

Preliminary IDs assigned to these metabolites

Models adjusted for age at blood draw, race, and sex and included subject and match-pair specific random effects