Showing posts from 2018

Atrial fibrillation associations from whole-genome sequence data now available in the CVDKP

We are pleased to present in the Cardiovascular Disease Knowledge Portal the results of a new study, published today in the Journal of the American Medical Association, that used deep-coverage whole-genome sequencing to uncover genetic variants contributing to early-onset atrial fibrillation. As part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium and the DiscovEHR study, first author Seung Hoan Choi and colleagues analyzed genetic associations with early-onset atrial fibrillation (AF) in 2,781 cases and 4,959 controls.

The study found multiple associations of common variants with AF, many of which supported previous reports. One particularly interesting association was found for a variant in an intron of the NAV2 gene. Since NAV2 is involved in nervous system development, this association may suggest a link between AF and development of the autonomic nervous system.

The researchers also took advantage of the whole-genome sequence data to assess the contribution of…

Heart failure and albuminuria associations across nearly 400,000 UK Biobank subjects now available in the CVDKP

Two new datasets now bring associations for heart failure and albuminuria from large UK Biobank subject pools to the Cardiovascular Disease Knowledge Portal (CVDKP). Both studies revealed important insights about the etiology of different aspects of cardiovascular disease. And the results of both studies are available now in the CVDKP--both integrated into the Portal, and as files of summary statistics for download.

The study of heart failure associations (Aragam et al. (2018), Circulation) looked at associations both with heart failure from any cause and with a more refined phenotype, nonischemic cardiomyopathy (NICM), defined as left ventricular dysfunction without coronary artery disease. The loci significantly associated with all-cause heart failure were predominantly those already known to be associated with heart failure risk factors, such as coronary artery disease and atrial fibrillation. However, refining the phenotype to NICM revealed a different spectrum of associations, ov…

See you at AHA!

This weekend, cardiovascular researchers from around the globe will be meeting in Chicago for the 2018 Scientific Sessions of the American Heart Association. For the Cardiovascular Disease Knowledge Portal team, this is an opportunity to meet and talk with the geneticists and biologists who use the site and get your input on how we can improve it.

Please come visit us at booth #2249 in the Exhibit Hall! We'll be there on Saturday, Nov. 10 from 11am-5pm; on Sunday, Nov. 11 from 10am-4:30pm; and on Monday, Nov. 12 from 10am-3pm.

Summary stat downloads and new features available in the CVDKP

We're pleased to announce the availability of summary statistic download files for several important association studies via the Cardiovascular Disease Knowledge Portal, as well as some new features in the Portal that help bring meaning to genetic association results.

Download files available

Full summary results from five studies may now be downloaded via the CVDKP Data page. Association results for atrial fibrillation, albuminuria, and several ECG traits are available, from these publications:

Haas et al. 2018, Genetic Association of Albuminuria with Cardiometabolic Disease and Blood Pressure.Prins et al. 2018, Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.Lin et al. 2018, Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.Christophersen et al. 2017, Fifteen Genetic Loci Associated With the Electrocardiographic P Wave.Christophersen et al. 2017, Large-scale analyses of common and rare vari…

Connect with the Knowledge Portal Network team at ASHG!

Next week, the human genetics research community will come together in San Diego for one of the most important conferences of the year: the annual American Society of Human Genetics meeting. The Knowledge Portal Network team will be there, and in addition to presenting all the new data and features in the Type 2 DiabetesCerebrovascular Disease, and Cardiovascular Disease Knowledge Portals (KPs), we'll be launching an entirely new Portal for the genetics of sleep disorders!

We'll also present an interactive workshop on Friday that will go over the basics of navigating the Knowledge Portal Network. Download the flyer here, and find more details below.

Here's the schedule of events for the week:

Tuesday, October 16
2:05-2:30 pm: Jason Flannick will present a talk, "Infrastructure for analyzing and disseminating large-scale genetic data for type 2 diabetes and other complex diseases," in the ASHG/IGES/ISCB Joint Symposium.
Room 6C - Upper Level/San Diego Convention …

Sign up for a hands-on tutorial session on the Knowledge Portals

Are you attending the American Society of Human Genetics meeting in October? If so, save your Friday lunch break for a tutorial session on the Knowledge Portals!

Navigating complex disease genetics: using the Knowledge Portal Network to move from SNPs to functional insights
12:30pm - 1:45pm
Friday, October 19
San Diego Convention Center
Room 28C, Upper Level

Bring your laptop and your questions about the Cardiovascular DiseaseCerebrovascular Disease, or Type 2 Diabetes Knowledge Portals (KPs). We'll go over some basics, illustrate workflows, and answer questions about how you can use KPs to investigate SNPs, genes, or regions of interest and turn genetic data into insights about complex diseases.

Please sign up so we can plan for refreshments. We'll send you a reminder a few days beforehand. We look forward to seeing you there! Please contact us with any questions or suggestions for topics you'd like to discuss.


New polygenic risk score data and new features in the CVDKP

Today there are several exciting developments for the Cardiovascular Disease Knowledge Portal. We now provide open access to files specifying risk scores for five major complex diseases, as described in a paper published today. Additionally, new interfaces that simplify the interpretation of genetic association data have been added to the CVDKP, making it easier to pinpoint variants and datasets that are informative for a disease or phenotype of interest.

Genome-wide polygenic risk score (GPS) variant weight files available in the CVDKP

One promise of the genomic era is that we will be able to predict from people's genotypes whether they are at risk of developing disease. Although this is now possible for some monogenic diseases, prediction of genetic risk for polygenic diseases has been more challenging. But a new paper, published today in Nature Genetics by Amit Khera, Mark Chaffin, and colleagues, brings us much closer to that goal for coronary artery disease, atrial fibrillatio…

Large new atrial fibrillation dataset now in the CVDKP

With today's publication of a new large-scale genetic association study (Roselli et al., Multi-ethnic genome-wide association study for atrial fibrillation, Nature Genetics (2018) doi:10.1038/s41588-018-0133-9), the corresponding dataset has been incorporated into the Cardiovascular Disease Knowledge Portal (CVDKP).

The new dataset, named 2018 AF HRC GWAS in the CVDKP, surveys more than 500,000 individuals, including over 65,000 with atrial fibrillation. With the majority of samples imputed to the Haplotype Reference Consortium (HRC) reference panel, the study analyzed associations for a total of more than 8 million common variants, nearly 3 million low-frequency variants, and almost 1 million rare variants. Individuals in the study represented a wide range of ancestries, including African American, East Asian, Hispanic, and Brazilian in addition to European.

With such a large sample size, the study had the power to detect many new associations. While about 30 loci associated with…

New PR interval genetic associations in the CVDKP

We've added a new dataset to the Cardiovascular Disease Knowledge Portal: PR interval exome chip analysis, with genetic associations from nearly 93,000 individuals. This study was published yesterday in Circulation: Genomics and Precision Medicine (Lin, H., et al., Circ Genom Precis Med. 2018;11:e002037).

The cardiac conduction system is critical to proper heart function, and abnormalities are associated with harmful conditions such as atrial fibrillation. One measure of cardiac conduction is the duration of the PR interval, defined as the time between the onset of the P wave and the onset of the QRS interval in an electrocardiogram. In this study, the authors measured the PR interval, in milliseconds, for 83,367 participants of European ancestry and 9,436 participants of African-American ancestry. They genotyped each participant using the Illumina Human Exome BeadChip, analyzed variant associations with PR interval, and performed meta-analyses.

Common and low-frequency variants (…

Join the Knowledge Portal Network team!

At the Knowledge Portal Network (currently consisting of the Type 2 Diabetes, Cerebrovascular Disease, and Cardiovascular Disease Knowledge Portals), we are looking for energetic, talented people to help us produce web portals that aggregate and serve genetic association results to the world in order to spark insights into complex diseases. There are positions open for a software engineer to help in developing and producing these web portals, and for a technical release manager to manage and coordinate tasks during production and maintenance of the portals.

The positions are located at the Broad Institute in Cambridge, MA, a dynamic and exciting work environment where cutting-edge science is applied to critical biomedical problems.

Find more details and apply for the software engineer or technical release manager positions at the Broad Careers site.