TY - JOUR T1 - An interaction map of circulating metabolites, immune gene networks and their genetic regulation JF - bioRxiv DO - 10.1101/089839 SP - 089839 AU - Artika P. Nath AU - Scott C. Ritchie AU - Sean G. Byars AU - Liam G. Fearnley AU - Aki S. Havulinna AU - Anni Joensuu AU - Antti J. Kangas AU - Pasi Soininen AU - Annika Wennerström AU - Lili Milani AU - Andres Metspalu AU - Satu Männistö AU - Peter Würtz AU - Johannes Kettunen AU - Emma Raitoharju AU - Mika Kähönen AU - Markus Juonala AU - Aarno Palotie AU - Mika Ala-Korpela AU - Samuli Ripatti AU - Terho Lehtimäki AU - Gad Abraham AU - Olli Raitakari AU - Veikko Salomaa AU - Markus Perola AU - Michael Inouye Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/11/26/089839.abstract N2 - The interaction between metabolism and the immune system plays a central role in many cardiometabolic diseases. We integrated blood transcriptomic, metabolomic, and genomic profiles from two population-based cohorts, including a subset with 7-year follow-up sampling. We identified topologically robust gene networks enriched for diverse immune functions including cytotoxicity, viral response, B cell, platelet, neutrophil, and mast cell/basophil activity. These immune gene modules showed complex patterns of association with 158 circulating metabolites, including lipoprotein subclasses, lipids, fatty acids, amino acids, and CRP. Genome-wide scans for module expression quantitative trait loci (mQTLs) revealed five modules with mQTLs of both cis and trans effects. The strongest mQTL was in ARHGEF3 (rs1354034) and affected a module enriched for platelet function. Mast cell/basophil and neutrophil function modules maintained their metabolite associations during 7-year follow-up, while our strongest mQTL in ARHGEF3 also displayed clear temporal stability. This study provides a detailed map of natural variation at the blood immuno-metabolic interface and its genetic basis, and facilitates subsequent studies to explain inter-individual variation in cardiometabolic disease. ER -