An interaction map of circulating metabolites, immune gene networks, and their genetic regulation

• DOI: 10.1186/s13059-017-1279-y
• Publication Date: 2017-08-01T15:01:37Z
• Authors: Artika P. Nath; Scott C. Ritchie; Sean G. Byars; Liam G. Fearnley; Aki S. Havulinna; Anni Joensuu; Antti J. Kangas; Pasi Soininen; Annika Wennerström; Lili Milani; Andres Metspalu; Satu Männistö; Peter Würtz; Johannes Kettunen; Emma Raitoharju; Mika Kähönen; Markus Juonala; Aarno Palotie; Mika Ala-Korpela; Samuli Ripatti; Terho Lehtimäki; Gad Abraham; Olli Raitakari; Veikko Salomaa; Markus Perola; Michael Inouye
• Keywords: Genome-wide Association Study

Immunometabolism plays a central role in many cardiometabolic diseases. However, robust map of immune-related gene networks circulating human cells, their interactions with metabolites, and genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, genomic profiles from two population-based cohorts (total N = 2168), including subset individuals matched multi-omic data at 7-year follow-up. We identify topologically replicable enriched for diverse immune functions cytotoxicity, viral response, B cell, platelet, neutrophil, mast cell/basophil activity. These modules show complex patterns association 158 lipoprotein subclasses, lipids, fatty acids, amino small molecules, CRP. Genome-wide scans module expression quantitative trait loci (mQTLs) reveal five mQTLs that have both cis trans effects. The strongest mQTL ARHGEF3 (rs1354034) affects platelet function, independent counts. Modules neutrophil function temporally stable metabolite associations over follow-up, providing evidence these constituent products may play roles metabolic inflammation. Furthermore, the also displays clear temporal stability, supporting widespread effects this locus. This study provides detailed natural variation immunometabolic interface its basis, facilitate subsequent studies to explain inter-individual disease.