The DIAGRAM (DIAbetes Genetics Replication And Meta-analysis) consortium is a grouping of researchers with shared interests in performing large-scale studies to characterise the genetic basis of type 2 diabetes, and a principal focus on samples of European descent. The membership and scope of DIAGRAM has developed as the scale of collaboration in the field has increased. The initial instance of DIAGRAM (retrospectively termed "DIAGRAM v1") enabled the combination of T2D genome wide association (GWA) studies from the UK (WTCCC), DGI and FUSION groups: this meta-analysis, and consequent replication, resulted in identification of six novel signals influencing T2D risk (Zeggini et al, Nature Genetics 2008). An incremental meta-analysis ("DIAGRAM v2" or "DIAGRAM+") adding GWA data from a further five studies (DGDG, KORA, Rotterdam, DeCODE, EUROSPAN for a total of 8,130 cases and 38,987 controls) together with extensive replication involving 20 other cohorts, was central to identification of a further 17 loci (Voight et al, Nature Genetics 2010; Dupuis et al, Nature Genetics 2010; Saxena et al, Nature Genetics 2010). Whilst in the Voight et al (2010) paper, GWA data from the Framingham, ARIC and NHS studies was only used for in silico replication, the full data from these studies was subsequently combined to constitute the largest current GWA dataset in samples of European descent ("DIAGRAMv3": 12,171 cases and 56,862 controls). This data set was used as the basis for the selection of SNPs for T2D replication for the Metabochip custom array, and a manuscript describing the integration of DIAGRAM v3 and Metabochip data (a combined total of ~150k individuals) was published in 2012 (Morris et al, Nature Genetics 2012). Summary data from this analysis are available at www.diagram-consortium.org.
In addition to these large discovery projects, DIAGRAM data have supported over 200 internal and external research projects. These include efforts to (a) further risk-allele identification within stratified subsets of the data (e.g. lean/obese, early/late onset); (b) perform fine-mapping within established susceptibility regions; (c) characterise pleiotropic and mechanistic overlaps between GWA data for diverse traits; (d) provide "lookups" for candidate gene studies; (e) support efforts at T2D variant discovery in other major ancestral groups (e.g. Kooner et al, Nature Genetics 2011; Cho et al, Nature Genetics 2012); and (f) integrate DIAGRAM findings with other genomic data (e.g. Small et al, Nature Genetics 2011).
DIAGRAM has strong links and substantial overlap of membership with the GoT2D and T2D-GENES consortia that are leading sequence-based discovery efforts for T2D. GWA, metabochip and exome chip data from existing and new DIAGRAM partners will provide valuable extension, replication and validation of findings arising from those studies. There are also strong links with equivalent efforts in other major ancestral groups (e.g. AGEN, MEDIA) that will enable further rounds of GWA integration that support locus discovery and causal variant fine mapping.