New T2DKP release adds individual-level data for interactive analysis

With the April release of the Type 2 Diabetes Knowledge Portal, we are increasing the number of datasets and samples available for interactive analysis via the LocusZoom and GAIT tools. These tools now access individual-level data from three additional datasets, all of which were quality controlled and analyzed at the Accelerating Medicines Partnership in Type 2 Diabetes (AMP T2D) Data Coordinating Center (DCC):

• BioMe AMP T2D GWAS: 9,173 multi-ancestry samples from the Charles Bronfman Institute for Personalized Medicine BioMe Biobank;

• CAMP GWAS: 3,628 multi-ancestry samples from the MGH Cardiology and Metabolic Patient cohort, generated by a public-private partnership between Pfizer Inc. and Massachusetts General Hospital;

• METSIM GWAS: 8,791 European ancestry samples from the Metabolic Syndrome in Men study.

These individual-level data are available as "dynamic" datasets, powered by Hail software, in LocusZoom on Gene pages and Variant pages of the T2DKP, for the following phenotypes: 

• BioMe AMP T2D GWAS: type 2 diabetes, BMI, diastolic blood pressure, fasting glucose, HbA1c, HDL cholesterol, LDL cholesterol, systolic blood pressure

• CAMP GWAS: type 2 diabetes, BMI, fasting glucose, fasting insulin

• METSIM GWAS: type 2 diabetes, BMI, diastolic blood pressure, fasting glucose, fasting insulin, HbA1c, HDL cholesterol, LDL cholesterol, systolic blood pressure

To perform interactive analyses on these data in LocusZoom, select one of the available phenotypes in step 1 and then choose a "dynamic" dataset in step 2.

When you click on a variant in the resulting LocusZoom plot, the option to condition on that variant appears in the tooltip:

Clicking on that link starts on-the-fly association analysis for the region while conditioning on that variant, which can reveal whether association signals are independent of each other. You can choose to condition on multiple variants. The variants of your choice are listed in the upper left-hand corner of the plot, and the list may be edited:

Individual-level data from these three datasets are also available for interactive analysis via the Genetic Association Interactive Tool (GAIT) on Variant Pages. After selecting one of the datasets, you will be able to choose a phenotype for association analysis, filter the sample pool by specifying a range of values for one or more phenotypes, choose custom covariates, and then run on-the-fly association analysis for your chosen subset of samples. Find all of the details about how to use this tool in our GAIT guide.

We hope that the increased ability to interact with individual-level data in the T2DKP will be helpful to your research. As always, we are happy to answer any questions about these or other data and tools; please contact us for help.

New release today, as the KPN moves to a regular release schedule

At the Knowledge Portal Network (consisting of the Type 2 Diabetes, Cardiovascular Disease, and Cerebrovascular Disease Knowledge Portals), we are establishing a regular bimonthly release schedule. Every other month, new data and features will be incorporated into the Portals. Today, we are pleased to announce the first of these releases.

New data in the Type 2 Diabetes Knowledge Portal

This release adds two new datasets to the T2DKP. The Diabetic Cohort - Singapore Prospective Study Program is a T2D case-control study to identify genetic and environmental risk factors for diabetes in Singapore Chinese. The DC-SP2 GWAS set, a meta-analysis of summary level T2D associations from 3,951 individuals, was contributed by Drs. Rob Martinus Van Dam, E Shyong Tai, and Xueling Sim from the National University of Singapore. They have also submitted individual-level data from this study to the Accelerating Medicines Partnership Data Coordinating Center (AMP DCC), and these data will be incorporated into the T2DKP after quality control and analysis are complete.

In addition to this set, we have incorporated the publicly available summary statistics from the DIAGRAM 1000G GWAS. This dataset, from the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis) consortium, is a meta-analysis of 26,676 T2D cases and 132,532 control participants from 18 GWAS (Scott RA, et al. An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. (2017) Diabetes 66:2888). Samples were imputed using the all ancestries 1000 Genomes Project reference panel.

More details about both of these datasets are available on our Data page.

New features specific to the Type 2 Diabetes Knowledge Portal

We have expanded the range of data available for interactive analysis by adding individual-level data from the CAMP GWAS, BioMe AMP T2D GWAS, and METSIM GWAS datasets to the dynamic analysis modules LocusZoom and GAIT (Genetic Association Interactive Tool). LocusZoom, powered by the Hail software developed at the Broad Institute as part of the AMP T2D project, allows you to perform custom association analysis while conditioning on specific variants or sets of variants.

GAIT offers alternative options for custom association analysis, such as filtering samples by their phenotypic characteristics (e.g., age, BMI, cholesterol levels) and choosing specific covariates. To date, seven different datasets comprised of over 67,000 samples are available for dynamic analysis in GAIT. These include datasets housed both at the AMP DCC (19k exome sequence analysis; CAMP GWAS; BioMe AMP T2D GWAS; METSIM GWAS) and at the EBI Federated node (EXTEND GWAS; Oxford Biobank exome chip analysis; GoDARTS Affymetrix GWAS).

We have also taken an initial step towards integration of the T2DKP with a new federated node, the T2DREAM database of epigenomic data relevant to T2D. In the near future, epigenomic data displayed in the T2DKP will be drawn dynamically from T2DREAM. In the meantime, we have added gene- and variant-specific links to T2DREAM from the re-styled External Resources section at the bottom of Gene and Variant pages.

New features for all Knowledge Portals

Some of the improvements in this release are visible in all the Portals of the Knowledge Portal Network. One of the most significant affects LocusZoom, the dynamic plot that displays variant associations along with their genomic coordinates, linkage disequilibrium, and other information. Previously, the only way to select a phenotype was to scroll through a long list. Now, a new phenotype filter lets you enter one or more search criteria and filter the list by those criteria. Once you have selected a phenotype, the datasets that include associations for that phenotype are presented for selection. Previously, only one dataset (the one with the largest sample size) was available for each phenotype; now, associations from all relevant datasets may be viewed in LocusZoom.

Portion of the updated LocusZoom interface, showing phenotype filtering capability.

The sample filtering panel of the user interface for the custom burden test and GAIT (Genetic Association Interactive Tool) has also been improved to make it more intuitive to use. The External Resources sections of Gene and Variant pages have been re-styled, and gene- and variant-specific links to PheWeb have been added. PheWeb displays phenotypes most significantly associated with the gene or variant, based on a GWAS for over 2,400 phenotypes in UK Biobank data that was performed by Ben Neale's group. Finally, the home pages of all the Portals have been redesigned to make the appearance of the disease-specific portals more distinct.


Please browse these new data and features, and let us know what you think!

New MGH Cardiology and Metabolic Patient Cohort data in the T2D Knowledge Portal

We are pleased to announce a new data set in the T2D Knowledge Portal, from the MGH Cardiology and Metabolic Patient Cohort (CAMP). These data were contributed by Pfizer, Inc. as part of a public-private partnership to generate genotype data for a cardiometabolic and prediabetic cohort. This data set adds individual-level genetic association data for type 2 diabetes (T2D), fasting glucose levels, and fasting insulin levels from more than 3,500 samples to the Portal knowledgebase. Association data for additional phenotypes from this cohort will be incorporated in the future.

The inclusion of this data set in the T2D Knowledge Portal illustrates the uniqueness of the Accelerating Medicines Partnership, which brings together pharmaceutical companies and non-profit institutions with the goal of speeding up the discovery of new targets for treatment of T2D. The pharmaceutical partners in this collaboration have committed not only to providing funding, but also to sharing the data they generate. The CAMP data set contributed by Pfizer is the first set from a pharmaceutical partner to be made available in the Portal.

Another unique aspect of this data set is that it is the first to be included in the Portal with “Early Access Phase 1” status, which is assigned to new data. This status denotes that although analysis and quality control checks have been performed, the data are not yet considered to be in their final state. During the early access period, users may analyze the data but may not submit the results of these analyses for publication. Find the full details about the different phases of data release on our Policies page.

The CAMP cohort consists of 3,857 subjects who were recruited at the Massachusetts General Hospital Heart Center between 2008 and 2012. In addition to genotyping, the subjects had either vascular reactivity measurements (for T2D patients) or an oral glucose tolerance test (for patients not known to have T2D), and samples of their plasma and serum were analyzed. Most of the subjects were of European ancestry; about 10% were African American.

The analysis and quality control processes for this data set were performed by the Analysis Team of the Accelerating Medicines Partnership Data Coordinating Center (AMP-DCC) at the Broad Institute, and are completely transparent and fully documented. The experiment design and analysis are summarized on our Data page, and detailed reports are available for download. Going forward, all new data sets added to the Portal will be fully documented in this manner.

One intriguing—and somewhat puzzling—result from the analysis highlights the utility of incorporating data sets like this one into the Portal. The variant most strongly associated with T2D (at genome-wide significance) in this set is located in the major histocompatibility complex region near the HLA-C gene.

Known associations of genes in this region with type 1 diabetes, along with a high local recombination rate, make it challenging to interpret the meaning of this association. However, it certainly merits further investigation because of its genome-wide significance. The inclusion of this data set in the Portal, in the context of all other available data about T2D associations in the region, greatly facilitates the further analysis of this and other associations in the set.

The CAMP data may be accessed via multiple interfaces in the Portal. They are shown in tables of summary statistics and accessible in variant searches using the Variant Finder. Importantly, since the data are individual-level, samples may be filtered by various parameters and used for custom association analysis in our Genetic Association Interactive Tool (GAIT).

Find CAMP data at all of these locations in the Portal:

• On Gene Pages (e.g.,  HLA-C) in the Variants & Associations table.
• On Variant Pages (e.g., rs9468919) in the Associations at a glance section and in the Association statistics across traits table.
• Via the Variant Finder tool, for the phenotypes T2D, fasting glucose, and fasting insulin.
• Via the Genetic Association Interactive Tool (GAIT), which enables custom association analysis for either single variants (available on Variant Pages) or for the set of variants in and near a gene (Interactive burden test, available on Gene Pages).