10.6084/m9.figshare.5127820.v1 Nakada T. Nakada T. Boyd J.H. Boyd J.H. Russell J.A. Russell J.A. Aguirre-Hernández R. Aguirre-Hernández R. Wilkinson M.D. Wilkinson M.D. Thair S.A. Thair S.A. Nakada E. Nakada E. McConechy M.K. McConechy M.K. Fjell C.D. Fjell C.D. Walley K.R. Walley K.R. Supplementary Material for: <b><i>VPS13D</i></b> Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock Karger Publishers 2015 VPS13D gene IL-6 Severe sepsis Septic shock Polymorphism Genome-wide association studies Lymphoblastoid cells 2015-04-17 00:00:00 Dataset https://karger.figshare.com/articles/dataset/Supplementary_Material_for_b_i_VPS13D_i_b_Gene_Variant_Is_Associated_with_Altered_IL-6_Production_and_Mortality_in_Septic_Shock/5127820 <b><i>Background:</i></b> Genetic variations contribute to septic shock mortality. To discover a novel locus, we performed in vitro genome-wide association studies (GWAS) and further tested the result in a cohort of septic shock patients. <b><i>Methods:</i></b> Two in vitro GWAS using a quantitative trait locus analysis of stimulated IL-6 production in lymphoblastoid cells from 60 individuals of European ancestry were performed. <i>VPS13D</i> rs6685273 was genotyped in European ancestry patients (n = 498). The <i>VPS13D</i> gene was silenced in vitro. <b><i>Results:</i></b> Two GWAS using lymphoblastoid cells identified the locus of <i>VPS13D</i> rs6685273 that was significant in the same direction in both GWAS. The <i>VPS13D</i> rs6685273 C allele was associated with increased IL-6 production. Patients with septic shock who had the <i>VPS13D</i> rs6685273 CC genotype had an increased 28-day mortality (p = 0.023) and more organ failure (p < 0.05) compared to the CT/TT genotypes. <i>VPS13D</i> in vitro gene silencing in the HeLa cell line increased IL-6 production. Furthermore, the rs6685273 genotype was associated with differential <i>VPS13D</i> splice variant expression. <b><i>Conclusions:</i></b> The <i>VPS13D </i>rs6685273 C allele was associated with increased IL-6 production in vitro. The patients with the <i>VPS13D </i>rs6685273 CC genotype had increased 28-day mortality and increased organ failure. <i>VPS13D</i> appears to regulate IL-6 production.