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Experimental Procedures Identification of SNPs We combined results from the six most recent meta-analyses identified from PubMed using the keywords ��GWAS,�� ��meta-analysis,�� ��diabetes,�� ��metabolic syndrome,�� and ��insulin resistance�� (Table S1 in Supplementary Material). The six meta-analyses had a total of 124 underlying genetic cohort studies (Table S1 in Supplementary Material). Selection of SNPs for analysis �C definition of a locus In total, 489 significant SNPs, identified CYTH4 in the meta-analyses, were used in the downstream analyses (Table S2 in Supplementary Material). SNPs within the same haplotype block were combined and named according to their locus. For our purposes, haplotype blocks were defined as all SNPs sharing linkage disequilibrium check details coefficients of at least 0.8 r2 or 0.8 D��. Each haplotype is named according to the genes within the block, thereby known as a locus. Literature searches for diabetes connections Each locus was assessed to determine if it had previously been associated to T2D. Previous associations to diabetes were identified by searches of the published literature (PubMed), disease databases (OMIM), and functional classification databases (Uniprot). In addition, the GWAS Catalog (NHGRI-EBI Catalog of published GWAS) was used to elucidate known GWAS SNPs for each spatial locus, citing any relevant SNPs to the metabolic syndrome that have been found in that locus (Figure ?(Figure11). Identification of spatial connections to diabetes The web-based programs GWAS3D (22) and HaploRegv2 (23) were used to identify physical connections [as captured by proximity ligation (24, 25)] between T2D SNPs and to identify which SNPs define a locus (see above for criteria). Identification of eQTL connections to diabetes We hypothesized that spatial associations between T2D GWAS SNPs and distant loci were regulatory. Therefore, we set about identifying significant SNP-dependent expression changes within the Hapmap3 dataset (population-adjusted microarray expression values from HapMap lymphoblastoid cell lines in each of the eight Hapmap populations). Significant associations were identified if the expression changes were (1) Nintedanib mouse significant (p?