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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 3.

Changes in Metabolites per Year in 282 Pre-Rheumatoid Arthritis (RA) Cases vs. 242 Controls for Metabolites with Differential Trajectories, 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 0.018 0.037 −0.372 3.06E-07 −0.071 2.60E-05 0.005*
Pregnenolone Steroids ±17-hydroxypregnenolone sulfate HMDB0000416 −0.040 0.002 −0.411 4.57E-07 −0.090 2.85E-04 0.015*
pregnenolone sulfate HMDB0000774 0.004 0.716 −0.410 1.51E-07 −0.069 8.40E-04 0.032*
Lipids Long Chain Fatty Acids hydroxymyristate HMDB0002261 −0.020 0.144 −0.321 1.16E-04 −0.088 1.25E-03 0.040*
Fatty Acid Metabolism (Acyl Carnitine) C2 carnitine HMDB0000201 0.173 8.08E-38 −0.170 0.017 −0.071 0.004 0.075
C9 carnitine HMDB0013288 0.008 0.524 −0.263 0.001 −0.075 0.003 0.062
Glycerophospholipids C40:7 phosphatidylethanolamine plasmalogen HMDB0011394 0.092 5.27E-12 −0.394 8.71E-07 −0.067 0.009 0.102
Amino Acid Leucine, Isoleucine and Valine Metabolism N-acetylleucine HMDB0011756 −0.042 0.003 0.250 5.13E-03 0.113 7.67E-05 0.007*
Tyrosine Metabolism tyramine HMDB0000306 −0.040 0.001 0.888 4.88E-25 0.083 2.67E-04 0.014*
Xenobiotics Food/ Plant Components levulinate HMDB0000720 0.136 3.66E-20 −0.524 2.40E-10 −0.117 3.48E-05 0.005*
Caffeine/Xanthine Metabolism 1,7-dimethyluric acid HMDB0011103 0.045 0.001 −0.148 0.074 −0.090 0.001 0.037*
theophylline HMDB0001889 0.033 0.016 −0.116 0.180 −0.079 0.003 0.072
caffeine HMDB0001847 0.045 0.001 −0.154 0.069 −0.085 0.002 0.046*
Drugs naproxen HMDB0001923 0.016 0.315 0.385 7.62E-06 0.100 0.002 0.044*

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