Integrative genetic and metabolite profiling analysis suggests altered phosphatidylcholine metabolism in asthma

Ried, J. S. and Baurecht, H. and Stueckler, F. and Krumsiek, J. and Gieger, C. and Heinrich, J. and Kabesch, M. and Prehn, C. and Peters, A. and Rodriguez, E. and Schulz, H. and Strauch, K. and Suhre, K. and Wang-Sattler, R. and Wichmann, H. -E. and Theis, F. J. and Illig, T. and Adamski, J. and Weidinger, S. (2013) Integrative genetic and metabolite profiling analysis suggests altered phosphatidylcholine metabolism in asthma. ALLERGY, 68 (5). pp. 629-636. ISSN 0105-4538, 1398-9995

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Abstract

Background Genome-wide association studies (GWAS) have identified many risk loci for asthma, but effect sizes are small, and in most cases, the biological mechanisms are unclear. Targeted metabolite quantification that provides information about a whole range of pathways of intermediary metabolism can help to identify biomarkers and investigate disease mechanisms. Combining genetic and metabolic information can aid in characterizing genetic association signals with high resolution. This work aimed to investigate the interrelation of current asthma, candidate asthma risk alleles and a panel of metabolites. Methods We investigated 151 metabolites, quantified by targeted mass spectrometry, in fasting serum of asthmatic and nonasthmatic individuals from the population-based KORA F4 study (N=2925). In addition, we analysed effects of single-nucleotide polymorphisms (SNPs) at 24 asthma risk loci on these metabolites. Results Increased levels of various phosphatidylcholines and decreased levels of various lyso-phosphatidylcholines were associated with asthma. Likewise, asthma risk alleles from the PDED3 and MED24 genes at the asthma susceptibility locus 17q21 were associated with increased concentrations of various phosphatidylcholines with consistent effect directions. Conclusions Our study demonstrated the potential of metabolomics to infer asthma-related biomarkers by the identification of potentially deregulated phospholipids that associate with asthma and asthma risk alleles.

Item Type: Article
Uncontrolled Keywords: GENOME-WIDE ASSOCIATION; VARIANTS; RISK; asthma; genetics; lipids; metabolomics
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Kinder- und Jugendmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 16 Apr 2020 05:47
Last Modified: 16 Apr 2020 05:47
URI: https://pred.uni-regensburg.de/id/eprint/16759

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