Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors

Abstract

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) of up to 8,293 Finns we identified 27 genome-widely significant loci (p < 1.2 × 10) for one or more cytokines. Fifteen of the associated variants had expression quantitative trait loci in whole blood. We provide genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link inflammatory markers with variants previously associated with autoimmune diseases such as Crohn disease, multiple sclerosis, and ulcerative colitis and hereby elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets.

Plasma levels of hepatocyte growth factor and placental growth factor predict mortality in a general population: a prospective cohort study

“…The assays were performed according to the manufacturer's instructions, with the exception that the quantity of beads, detection antibodies and streptavidin–phycoerythrin conjugate was used at 50% of the recommended concentration. This was found to be sufficient in our preliminary assays and has been applied in other biomarker projects . An eight‐point standard curve using recombinant proteins was generated for each growth factor.…”

Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

“…Genome-wide association (GWA) analyses could identify these genes or variants. There are several GWA studies of FA (Elliott et al, 2017;Lopez et al, 2012;Sprooten et al, 2013Sprooten et al, , 2014 and inflammatory measures (Ahola-Olli et al, 2017;Emilsson et al, 2018;Folkersen et al, 2017;Kim et al, 2012;Larsen et al, 2013;Li et al, 2016;Sun et al, 2018). While these analyses successfully identify loci underlying individual variation in these traits, they fail to identify variants common to both.…”

Informed dimension reduction of clinically-related genome-wide association summary data characterises cross-trait axes of genetic risk

“…17,18 On the seropositive side, we saw significant results for pernicious anemia, a disease strongly associated with anti-gastric parietal cell and anti-Intrinsic Factor antibodies, as well as with autoimmune thyroiditis, T1D and vitiligo. 19 To help characterise the biology captured by individual components we projected additional datasets: blood counts, 20 immune cell counts 21 and serum cytokine concentrations 22 (Supplementary Tables 5, 6 and 7). We expect that significant results will occur when the projected score is a composite of many small effects working in consistent directions.…”