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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 2.

Changes in Relative Metabolites per year in 292 Pre-Rheumatoid Arthritis (RA) Cases and 291 Controls for Metabolites with Differential Trajectories over Time (at p<0.005 and FDR q<0.05)

Time Group
Pre-RA Cases vs. Controls		 Interaction
Time*Pre-RA Status
Super Class Sub Pathway Name HMDB ID β T p β G p β Intx p q
Steroids Androsterone Glucuronides ±androsterone glucuronide HMDB0002829 0.017 0.046 −0.359 1.7E-07 −0.074 4.9E-06 1.39E-03
Pregnenolone Steroids ±17-hydroxypregnenolone sulfate HMDB0000416 −0.046 1.48E-04 −0.398 2.0E-07 −0.086 3.8E-04 0.020
pregnenolone sulfate HMDB0000774 0.001 0.939 −0.390 1.1E-07 −0.064 0.001 0.037
Lipids Long Chain Fatty Acids hydroxymyristate HMDB0002261 −0.016 0.239 −0.349 1.2E-05 −0.089 0.001 0.017
Fatty Acid Metabolism (Acyl Carnitine) C2 carnitine HMDB0000201 0.178 6.27E-43 −0.127 0.067 −0.075 0.002 0.045
C9 carnitine HMDB0013288 0.009 0.460 −0.275 0.000 −0.077 0.002 0.039
Glycerophospholipids C40:7 phosphatidylethanolamine plasmalogen HMDB0011394 0.096 2.00E-14 −0.371 0.000 −0.075 0.003 0.049
Amino Acids Leucine, Isoleucine and Valine Metabolism N-acetylleucine HMDB0011756 −0.043 0.002 0.251 0.003 0.115 0.000 0.004
Tyrosine Metabolism tyramine HMDB0000306 −0.036 0.001 0.865 0.000 0.082 0.000 0.016
Xenobiotics Food/Plant Components levulinate HMDB0000720 0.139 6.14E-23 −0.489 8.5E-10 −0.118 1.7E-05 0.002
Caffeine/Xanthine Metabolites 1,7-dimethyluric acid HMDB0011103 0.044 0.001 −0.181 0.022 −0.091 0.001 0.028
theophylline HMDB0001889 0.033 0.010 −0.163 0.047 −0.083 0.002 0.040
caffeine HMDB0001847 0.046 3.82E-04 −0.184 0.023 −0.084 0.001 0.037
Drugs naproxen HMDB0001923 0.022 0.145 0.390 1.6E-06 0.096 0.001 0.038

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

C: Carbon

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

±

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