A genome-wide functional genomics approach uncovers genetic determinants of immune phenotypes in type 1 diabetes

Background: The large inter-individual variability in immune-cell cell composition and function determines immune responses in general and susceptibility to immune-mediated diseases in particular. While much has been learned about the genetic variants relevant for type 1 diabetes (T1D), the pathophysiological mechanisms through which these variations exert their effects remain unknown.
Methods: Blood samples were collected from 243 patients with T1D of Dutch descent. We applied genetic association analysis on > 200 immune cell traits and >100 cytokine production profiles in response to stimuli measured to identify genetic determinants of immune function, and compared the results obtained in T1D to healthy controls.
Results: Genetic variants that determine susceptibility to T1D significantly affect T cell composition. Specifically, the CCR5+ regulatory T cells associate with T1D through the CCR region, suggesting a shared genetic regulation. Genome-wide quantitative trait loci (QTL..., The QTL dataset was generated by mapping immune phenotypes (cell proportion and cytokine production in response to stimulation) to either heathy donors (500FG) or Type 1 diabetes patients (300DM)., All donor information was Anonymized.