Metabolome-wide Association Study with Habitual Physical Activity in Four Prospective Cohort Studies.

Am J Epidemiol 2019 Jul 31. Epub 2019 Jul 31.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

In this study, we identified plasma metabolites associated with habitual physical activity among 5197 U.S. participants from the Nurses' Health Study (NHS), NHSII, and the Health Professional Follow-up Study (HPFS). Physical activity was assessed every 2-4 years by self-reported questionnaires. Blood was collected in the NHS between 1989-1990, NHSII during 1996-1999, and the HPFS during 1993-1995. Metabolic profiling was conducted by liquid chromatography-mass spectrometry (LC-MS). Our study included 337 known metabolites, with 256 of them classified as lipids. We corrected for multiple testing by controlling the tail probability of the proportion of false positives (TPPFP) and accounted for correlated tests using bootstrapping. We independently replicated the identified metabolites among 2305 women in the Women's Health Initiative (WHI) in 1993. After adjusting for multiple variables including body mass index, physical activity was significantly associated with 20 metabolites after correcting for multiple testing (TPPFP<0.05). Specifically, physical activity was positively associated with two amino acids (citrulline and glycine), four cholesteryl esters [CEs] (C18:2, C18:1, C16:0, and C18:3), eight phosphocholines [PCs] and lysophosphatidylcholines [LPCs] (C36:4 PC-A, C34:3 PC plasmalogen, C36:3 PC plasmalogen, C34:2 PC plasmalogen, C36:2 PC, C18:2 LPC, C20:5 LPC, and C18:1 LPC), and three phosphatidylethanolamines [PEs] and lysophosphatidylethanolamines [LPEs] (C18:2 LPE, C18:1 LPE, and C38:3 PE plasmalogen). Half of the identified metabolites were replicated in the WHI. Our study may help identify biomarkers of physical activity and provide insight into biological mechanisms underlying the beneficial effect of being physically active on cardiometabolic health.

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http://dx.doi.org/10.1093/aje/kwz171DOI Listing
July 2019
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