Biology subjects

Peter Würtz

Publications and source records attributed to Peter Würtz.

3 recordsLinked to original sources

bioRxiv2016

Genome-wide association study identifies 17 new loci influencing concentrations of circulating cytokines and growth factors

Circulating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) up to n=8,293 Finns we identified 27 loci with genome-wide association (P-value<1.2x10-9) for one or more cytokines, including 17 unidentified in previous GWASes. Fifteen of the associated SNPs had expression quantitative trait loci in whole blood. We provide strong genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link known autoimmune disease variants including Crohn's disease, multiple sclerosis and ulcerative colitis with new inflammatory markers, which elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets.

Genomics↗

bioRxiv2016

Metabolic profiling of alcohol consumption in 9778 young adults

BackgroundHigh alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults.\n\nMethodsCross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays.\n\nResultsIncreased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P<0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U-shaped associations with alcohol consumption. Results were coherent for men and women, consistent across the three cohorts, and similar if adjusting for body mass index, smoking and physical activity. The metabolic changes accompanying change in alcohol intake during follow-up resembled the cross-sectional association pattern (R2=0.83, slope=0.72{+/-}0.04).\n\nConclusionsAlcohol consumption is associated with a complex metabolic signature, including aberrations in multiple biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with long-term changes in alcohol consumption. These results elucidate the double-edged effects of alcohol on cardiovascular risk.\n\nKey messagesO_LIAlcohol intake in young adults associates with multiple novel metabolic biomarkers for the risk of cardiovascular disease and type 2 diabetes. The metabolic aberrations are mainly adversely related to cardiometabolic risk\nC_LIO_LIProminent metabolic associations with alcohol consumption include monounsaturated fatty acids, omega-6 fatty acids, glutamine, citrate and lipoprotein particle size. Many of these cardiometabolic biomarkers were as strongly associated with alcohol intake as HDL cholesterol\nC_LIO_LIThe strongest novel biomarkers of alcohol consumption followed linear association shapes, whereas many lipid measures displayed U-shaped associations\nC_LIO_LIThe detailed metabolic signature of alcohol consumption tracked with long-term changes in alcohol use, suggesting that the observed metabolic changes are at least partly due to alcohol consumption\nC_LIO_LIThe results provide improved understanding of the diverse molecular processes related to alcohol intake. Novel metabolic biomarkers reflecting both alcohol intake and cardiovascular risk could serve as intermediates that may help to bridge the complex relation between alcohol and cardiometabolic risk\nC_LI

Systems Biology↗

bioRxiv2015

Systems medicine links microbial inflammatory response with glycoprotein-associated mortality risk

Integrative analyses of high-throughput omics data have elucidated the aetiology and pathogenesis for complex traits and diseases1-4, and the linking of omics information to electronic health records promises new insights into human health and disease. Recent nuclear magnetic resonance (NMR) spectroscopy biomarker profiling has implicated glycoprotein acetyls (GlycA) as a biomarker for cardiovascular risk5 and all-cause mortality6. To elucidate biological processes contributing to GlycA-associated mortality risk, we leveraged human omics data from three population-based cohorts together with nation-wide Finnish hospital and mortality records. Elevated GlycA was associated with myriad infection-related inflammatory processes. Within individuals, elevated GlycA levels were stable over long time periods, up to a decade, and chronically elevated GlycA was also associated with modest elevation of numerous cytokines. Individuals with elevated GlycA also showed increased expression of a transcriptional sub-network, the Neutrophil Degranulation Module (NDM), suggesting an increased activity of microbe-driven immune response. Subsequent analysis of nation-wide hospitalisation and death records was consistent with a microbial basis for GlycA-associated mortality, with each standard deviation increase in GlycA raising an individuals future risk of hospitalization and death from non-localized infection by 40% and 136%, respectively. These results show that, beyond its established role in acute-phase response7-9, elevated GlycA is more broadly a biomarker for low-grade chronic inflammation and increased neutrophil activity. Further, increased risk of susceptibility to severe microbial-infection events in healthy individuals suggests this inflammation is a contributor to mortality risk. Taken together, this study demonstrates the power of an integrative approach that combines omics data and health records to delineate the biological processes underlying a newly discovered biomarker, providing a model strategy for future systems medicine studies.

Genomics↗