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Supplementary Material The Supplementary Material for this article can be found online at http://journal.frontiersin.org/article/10.3389/fendo.2015.00102 Click here for additional data file.(760K, PDF) Acknowledgments The authors would like to thank Associate Prof. Tony Merriman (University of Otago) for useful comments on this manuscript. This work was supported by an Auckland University Future Research Development Fund grant (3702119 to JO) and a University of Auckland Scholarship NLG919 concentration (WS)."ified 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 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 Verteporfin cell line 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 Tubulin 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) significant (p?