Tuesday, October 25, 2016

Design your own association analysis with our Genetic Association Interactive Tool (GAIT)

Genetic association analysis—identifying polymorphisms in the human genome that are correlated with altered risk of disease—is a powerful method for discovering disease mechanisms. These polymorphisms can indicate what goes wrong at the cellular level in the disease process, knowledge that is critically important for developing better diagnostics and therapies.

The Type 2 Diabetes Knowledge Portal offers a wealth of pre-calculated information on genetic associations between variants and type 2 diabetes (T2D) or other related traits. These results are computed using broadly defined groups of samples: either an entire sample set from a project, or ancestry-specific cohorts. This approach, while it generates very valuable results, masks effects that could only be detected in even more narrowly defined groups: for example, individuals within a certain range of age, body mass index, or cholesterol level. 

Until now, analysis of such fine-grained subsets of individual-level data has only been possible for expert geneticists with access to protected data. But our new Genetic Association Interactive Tool (GAIT) offers everyone an unprecedented amount of access to individual-level data along with an easy-to-use interface for analyzing genetic associations using custom subsets of samples and variants.

Two versions of GAIT are available in the Portal. One, on Variant pages (see an example) computes association statistics for the single variant featured on that page. The other, accessible on Gene pages (see an example) powers an interactive burden test that considers the collection of variants in or near a gene, or a selected subset of those variants. 

Where to find GAIT on Gene pages (left) and Variant pages (right)


The GAIT interface offers incredible flexibility for designing custom analyses. In the interactive burden test, you can filter variants by their predicted effects, or pick and choose individual variants to include. When creating sample sets for either single-variant association analysis or a gene burden test, you can specify a gender, set ranges for the values for multiple phenotypes, and choose principal components or phenotypes to use as covariates. And all these parameters may be set differently for different ethnic groups.

The GAIT interface displays phenotype values within the sample set and allows you to filter samples by multiple criteria


Once you set parameters of your choice, GAIT computes associations on the fly, based on individual-level data. To protect patient confidentiality, GAIT will not display results from sample sets consisting of fewer than 100 individuals.

To help you get familiar with this versatile tool, we’ve created a User Guide (download PDF) that summarizes all the details of the interface. Please give GAIT a try and let us know what you think!



Tuesday, October 18, 2016

New and updated data in the T2D Knowledge Portal

As members of the T2D Knowledge Portal team arrive in Vancouver for the American Society of Human Genetics meeting, we are pleased to announce that we have added a new data set to the Portal and made extensive updates to existing data sets. 

The new data set, named “CAMP GWAS” in the Portal, comes 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, and were analyzed by the Analysis Team of the Accelerating Medicines Partnership Data Coordinating Center (AMP-DCC) at the Broad Institute. The set adds individual-level genetic association data for type 2 diabetes (T2D), fasting glucose levels, and fasting insulin levels from nearly 3,500 samples to the Portal knowledgebase, and association data for more phenotypes will be added in the future.

CAMP data may be accessed on Gene and Variant pages in the Portal and via the Variant Finder, and may also be filtered and queried using the Genetic Association Interactive tool (GAIT).

Several other data sets in the Portal have been updated and improved:
  • The size of the CARDIoGRAM GWAS data set has nearly doubled, now consisting of 184,305 samples, and the data analysis has been updated.
  • The size of the CKDGen GWAS data set has also nearly doubled, to 133,814 samples; the data analysis has been updated; new subsets have been added that stratify serum creatinine associations by African American ancestry and stratify both serum creatinine and urinary albumin-to-creatinine ratio by the presence or absence of T2D.
  • The data set previously named “DIAGRAM GWAS” in the Portal has been updated and re-named “DIAGRAM Trans-ethnic meta-analysis;” its sample size has increased to 149,821. Several new subsets have been added, including gender-stratified, MetaboChip, and fine mapping data.
  • The GIANT GWAS data have been updated and European cohorts have been added for BMI and height traits.
  • The GLGC GWAS data set has increased in size to 188,577 samples and has been updated.
  • The number of samples in the MAGIC GWAS dataset has more than doubled, to 133,010; the data have been updated, and associations with 2 hour glucose, fasting glucose, and fasting insulin have been added for MetaboChip data.
Full details about all of these data sets are available on our Data page.

Because of compatibility issues with the updated data, we have temporarily removed the “GWAS results summary” section from Gene pages of the Portal. This feature will be restored within the next week.

As always with major updates, issues or bugs may have been introduced and we may not have found all of them during our routine testing. We encourage you to let us know of any problems that you encounter in using the Portal, and we welcome your questions and suggestions.

Friday, October 14, 2016

See you at ASHG 2016!

Members of the Type 2 Diabetes Knowledge Portal team will be attending the American Society of Human Genetics meeting next week in Vancouver, BC. You can catch us nearly every day of the meeting:

Tuesday 10/18

3 PM: Nöel Burtt will be one of the speakers in an informational session on the T2D Knowledge Portal and new funding opportunities offered by the Foundation for the NIH. Complimentary snacks, beer, and wine will be served! Please pre-register here.

Wednesday 10/19

10 AM - 4 PM: Find us in the exhibit hall at booth #428. We’ll be there to answer your questions and give tours and tutorials on the Portal.

Thursday 10/20

10 AM - 4 PM: We will again be in the exhibit hall at booth #428.

2 - 3 PM: Ryan Koesterer will present his poster on an automatic, scaleable quality control method for genetic association data that improves on current “gold-standard” methods (program #1943T).

2 - 3 PM: Maria Costanzo will present her poster giving an overview of data in the Portal and the global collaborative efforts behind its aggregation (program #329T).

Friday 10/21

10 AM - 4 PM: This is our last day in the exhibit hall at booth #428.

2 - 3 PM: Marcin von Grotthuss will present his poster on improving predictions of significant variants by taking protein structure into account (program #489F).

3 - 4 PM: Ben Alexander will present his poster on the software platform that powers the T2D Knowledge Portal user interface and custom analysis tools (program #1650F).

T2D Knowledge Portal staff attending ASHG

We look forward to meeting you at ASHG! If you have questions and cannot meet us any of these times, or if you won’t be at ASHG, our mailbox is always open at help@type2diabetesgenetics.org.

Monday, October 3, 2016

Come to a T2D Knowledge Portal information session at ASHG

The American Society of Human Genetics meeting is happening in Vancouver, B.C. in a little over two weeks! The Portal team will be presenting and exhibiting at multiple venues at ASHG, and the first event will take place immediately before the conference starts: an information session including an overview of the Accelerating Medicines Partnership in Type 2 Diabetes, a progress update on T2D Knowledge Portal functionality, and information on new funding opportunities. Complimentary hors d'oeuvres, beer and wine will be served!

Information session
Tuesday - October 18, 2016
3:00 pm - 4:00 pm PDT
Fairmont Waterfront

900 Canada Place Way

Vancouver, British Columbia


Please register here for this free event, hosted by FNIH.  Contact Nicole Spear at Nspear@fnih.org with any questions.

Watch this space over the next two weeks for a complete listing of opportunities to learn about the Portal and talk with the Portal team at ASHG!