Research Paper Volume 11, Issue 14 pp 5124—5139
Novel serum metabolites associate with cognition phenotypes among Bogalusa Heart Study participants
- 1 Department of Epidemiology, Tulane University, New Orleans, LA 70112, USA
- 2 Institute of Clinical Medical Science, China-Japan Friendship Hospital, National Clinical Research Center of Respiratory Diseases, Beijing, China
- 3 Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA 30602, USA
- 4 Children's Minnesota Research Institute, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA
- 5 School of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
- 6 Metabolon, Inc., Durham, NC 27560, USA
Received: May 11, 2019 Accepted: July 12, 2019 Published: July 21, 2019
https://doi.org/10.18632/aging.102107How to Cite
Copyright © 2019 Shi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Metabolomics study provides an opportunity to identify novel molecular determinants of altered cognitive function.
Methods: During 2013 to 2016 Bogalusa Heart Study (BHS) visit, 1,177 participants underwent untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy metabolomics profiling. Global cognition and five cognition domains were also assessed. The cross-sectional associations of single metabolites with cognition were tested using multiple linear regression models. Weighted correlation network analysis was used to examine the covariable-adjusted correlations of modules of co-abundant metabolites with cognition. Analyses were conducted in the overall sample and according to both ethnicity and sex.
Results: Five known metabolites and two metabolite modules robustly associated with cognition across overall and stratified analyses. Two metabolites were from lipid sub-pathways including fatty acid metabolism [9-hydroxystearate; minimum P-value (min-P)=1.11×10-5], and primary bile acid metabolism (glyco-alpha-muricholate; min-P=4.10×10-5). One metabolite from the glycogen metabolism sub-pathway (maltose; min-P=9.77×10-6), one from the polyamine metabolism sub-pathway (N-acetyl-isoputreanine; min-P=1.03×10-5), and one from the purine metabolism sub-pathway (7-methylguanine; min-P=1.19×10-5) were also identified. Two metabolite modules reflecting bile acid metabolism and androgenic steroids correlated with cognition (min-P=5.00×10-4 and 3.00×10-3, respectively).
Conclusion: The novel associations of 5 known metabolites and 2 metabolite modules with cognition provide insights into the physiological mechanisms regulating cognitive function.