Monday, January 23, 2017

Insulin Sensitivity Index data added to the Portal

The loss of sensitivity to insulin, often termed insulin resistance, is characteristic of type 2 diabetes. Since this sensitivity is difficult to measure directly, researchers have developed an index that reflects it: the modified Stumvoll Insulin Sensitivity Index (ISI). The index is derived by a formula that combines fasting insulin levels with glucose and insulin levels measured two hours after a glucose load.

Now, the results of a study of genetic associations of variants with ISI are available in the T2D Knowledge Portal. These results are from a recent paper in Diabetes by co-first authors Geoffrey Walford, Stefan Gustafsson, Denis Rybin, and fellow members of the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). (For an overview of the results, see our blog post about the paper.)

In this study, ISI was calculated for 16,753 non-diabetic individuals, and associations of their variants with ISI values were analyzed. The associations were adjusted in one of three ways: for age and sex; for age, sex, and body mass index (BMI); or according to a model that analyzed the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI. More details about this data set and others from MAGIC may be found on our Data page.

ISI associations are a subset of the MAGIC GWAS data set. They may be viewed in the Portal by selecting one of these phenotypes:
  • ISI adjusted for age-sex
  • ISI adjusted for age-sex-BMI
  • ISI adjusted for genotype-BMI interaction
Associations with these phenotypes can be found in these locations on Portal pages:
  • On Gene Pages (see an example) in the Variants & Associations table
  • On Variant Pages (see an example) in the Associations at a glance section and in the Association statistics across traits table
  • Via the Variant Finder tool, for the phenotypes listed above
  • A "Manhattan plot" of associations across the genome may be seen by selecting one of the phenotypes listed above in the View full genetic association results for a phenotype scroll box on the Portal home page.

Thursday, January 19, 2017

CAMP GWAS data set moves to Early Access Phase 2

Three months ago, we incorporated a data set from the MGH Cardiology and Metabolic Patient Cohort (CAMP) into the T2D Knowledge Portal. These data were contributed by Pfizer, Inc. as part of a public-private partnership to generate genotype data for a cardiometabolic and prediabetic cohort; they add 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. Now, the CAMP GWAS data set has transitioned to Early Access Phase 2 status in the Portal.

The CAMP GWAS data set was the first to be included in the Portal with “Early Access” status, which is assigned to new data. As described on our Policies page, all newly added data sets have Early Access status for the first six months that they are in the Portal. In the first three months, Phase 1 of the Early Access period, the data have undergone quality control checks but they are not considered to be in their final form. The purpose of Phase 1 is to allow Portal users to review and analyze the data in order to identify any potential problems or areas needing further analysis. After this three-month period, data sets move to Phase 2, indicating that the data are in final form and are fully integrated into the Portal.

Portal users must not submit manuscripts concerning new data until both Phase 1 and Phase 2 of the Early Access period have passed, and any results of analyses or proposed publications are subject to the "Fort Lauderdale Principles" articulated for the sharing of genomic data.

In three months, the CAMP GWAS data set will become Open Access, meaning that it may be freely used for research as long as Portal users comply with our guidelines on user responsibilities and proper citation. It is important to note that in order to protect patient privacy, individual-level data in the Portal are never directly accessible to users. Rather, the Portal makes available summary statistics derived from the data, and also provides tools (such as the Genetic Association Interactive Tool (GAIT) and the Interactive Burden Test) that allow users to perform custom analyses based on individual-level data while protecting the security and privacy of those data.

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).
  • A "Manhattan plot" of genetic associations across the genome may be accessed by selecting the phenotype T2D, fasting glucose, or fasting insulin in the "View full genetic association results for a phenotype" selection box on our home page, and then choosing the CAMP GWAS data set.

Find many more details about the CAMP GWAS data set on our Data page, or read a summary in this blog post.

Tuesday, January 17, 2017

New Year, New Data: BioMe AMP T2D GWAS

We’re happy to announce the first addition of data to the Type 2 Diabetes Knowledge Portal in 2017: the BioMe AMP T2D GWAS data set. The generation of these data was funded by the Accelerating Medicines Partnership in Type 2 Diabetes (AMP T2D), a collaboration between multiple stakeholders that aims to catalyze the clinical translation of genetic discoveries by producing and aggregating data, developing and implementing novel analytical methods and tools, and building infrastructure for data storage and presentation.

The BioMe AMP T2D GWAS data set is the first set to be entirely produced by the AMP T2D project, which supplied the funding and carried out every step of its production, from data generation to analysis, quality control, and presentation. Its immediate availability in the Portal, prior to publication, fulfills the mission of AMP T2D to speed up access to and utilization of new data.

These data were generated at the Charles Bronfman Institute for Personalized Medicine BioMe BioBank, a biorepository located at the Mount Sinai Medical Center (MSMC) in the upper Manhattan area of New York City. MSMC serves a diverse population of over 800,000 outpatients each year. Importantly, since many BioMe participants are African American or Hispanic Latino, this data set adds significant ethnic diversity to the Portal’s genetic association data.

The BioMe AMP T2D GWAS data set is comprised of about 13,000 unique individuals, 41.5% of whom are admixed American, 38% African American, and 20% European. Subjects were genotyped using at least one of three platforms: the Illumina Exome Array, the Illumina GWAS array, or the Affymetrix GWAS array. Their T2D status was assessed by an algorithm, and many additional traits were also measured.

The data were subjected to quality control and association analysis by the Analysis Team at the AMP Data Coordinating Center (DCC) at the Broad Institute. Variant associations with T2D, fasting glucose levels, and HbA1c levels were analyzed. The top results included both previously known and novel variants, with only a single variant reaching genome-wide significance: T2D association of the variant rs7903146, within the well-established T2D risk gene TCF7L2. Now that these results are available in the T2D Knowledge Portal, the ability to analyze them further in the context of all other available T2D association data may lead to additional insights.

The BioMe AMP T2D GWAS data currently has the “Early Access Phase 1” status that 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. More information about the data set, along with links to download even more detailed reports on its quality control and analysis, may be found in the BioMe AMP T2D GWAS section of our Data page.

BioMe AMP T2D GWAS data are available at these locations in the Portal:

  • On Gene Pages (see an example) in the Variants & Associations table and the Minor allele frequencies across data sets table
  • On Variant Pages  (see an example) in the Associations at a glance section and in the Association statistics across traits table
  • Via the Variant Finder tool, for these phenotypes: type 2 diabetes; fasting glucose adjusted for age and sex; HbA1c adjusted for age and sex; and HbA1c adjusted for age, sex, and body mass index
  • A "Manhattan plot" of associations across the genome may be seen by selecting one of the phenotypes above in the View full genetic association results for a phenotype scroll box on the Portal home page, and then selecting the BioMe AMP T2D GWAS data set.

As always, please contact us with any questions, comments, or suggestions.