Exciting new exome collection now in the T2DKP, along with new datasets and features

The latest release of the Type 2 Diabetes Knowledge Portal includes seven new or updated datasets and several new features.

The highlight of this release is the largest collection of disease-specific exomes to date: exome sequences from 20,791 T2D cases and 24,440 controls, from the AMP T2D-GENES collaboration (Flannick et al., 2019). As well as generating T2D association statistics for individual variants, the analysis produced gene-level T2D association scores that can help prioritize research into new drug targets. These associations are available on a new page of the T2DKP, accessible from the home page. Select "View gene associations":

to view a table listing gene-level association scores:

The table may be filtered by using any of 7 different filters or two aggregation tests. Full details of the filters and methods are described in the preprint. Individual-level data from the AMP T2D-GENES exome sequence analysis dataset are also available for secure custom analysis in the Custom burden test (accessible on Gene pages) and Genetic Association Interactive Tool (GAIT; available on Variant pages).

Many other new and updated datasets are included in this release:

• We've done further analysis of the BioMe AMP T2D GWAS dataset to generate associations for three complications of T2D: chronic kidney disease in diabetics, end-stage renal disease in diabetics, and diabetic neuropathy. 

• The FinnMetSeq exome sequence analysis dataset (Locke et al., 2019) includes associations for more than 60 phenotypes, many of them new to the T2DKP, from nearly 20,000 samples.

• MEDIA T2D GWAS
 is a meta-analysis of T2D associations in over 23,000 individuals of African American ancestry (Ng et al., 2014).

• VATGen GWAS (Chu et al., 2017), which includes associations for several fat distribution phenotypes, has been updated with sex-stratified cohorts
.

• 
Liver function GWAS (Chambers et al., 2011) analyzed more than 61,000 samples for associations with four liver enzymes.

• Genetic Factors for Osteoporosis Consortium GWAS
 (Morris et al., 2019) includes associations for estimated bone mineral density and fracture for more than 426,000 UK Biobank participants.

Find more information about each of these datasets on the T2DKP Data page. Results from each of these studies may be viewed in Interactive Manhattan plots and on Gene and Variant pages, and may be searched using the Variant Finder tool.

This release also includes several new features for the T2DKP. In addition to the new page of gene-level results for the AMP T2D-GENES exome sequence analysis dataset, described above, we've added:

• Bottom-line p-values for variant associations across different phenotypes, available as an additional option in the PheWAS plot on the Variant page. These associations are derived from a new analysis method, based on METAL, that meta-analyzes all datasets in the T2DKP while taking into account the overlaps between sample sets.

• A new Analysis modules page
, linked from the T2DKP home page, that provides quick access to tools. Currently, the tools available from this page are the Interactive Manhattan Plot, the Variant Finder, and the Genetic Risk Score tool; more will be added in the near future.

• In response to feedback from T2DKP users, we've changed the Common variants tab on the Gene page (which only displayed variants whose minor allele frequency was greater than 5%) to a Top variants
 tab, showing the most significantly associated variants regardless of MAF.

Please contact us with any questions or comments about this new release!