Wednesday, 30 March 2016

GWAX:Case-control association mapping without cases PREPRINT

This should be of interest to many!


The case-control association study is a powerful method for identifying genetic variants that influence disease risk. However, the collection of cases can be time-consuming and expensive; in some situations it is more practical to identify family members of cases. We show that replacing cases with their first-degree relatives enables genome-wide association studies by proxy (GWAX). In randomly-ascertained cohorts, this approach enables previously infeasible studies of diseases that are rare in the cohort, and can increase power to detect association by up to 30% for diseases that are more common in the cohort. As an illustration, we performed GWAX of 12 common diseases in 116,196 individuals from the UK Biobank. By combining these results with published GWAS summary statistics in a meta-analysis, we replicated established risk loci and identified 17 newly associated risk loci: four in Alzheimer's disease, eight in coronary artery disease, and five in type 2 diabetes. In addition to informing disease biology, our results demonstrate the utility of association mapping using family history of disease as a phenotype to be mapped. We anticipate that this approach will prove useful in future genetic studies of complex traits in large population cohorts.

Monday, 14 March 2016

Elephants are resistant to cancer

Whole-genome sequencing of 644 elephant tissue samples using the HiSeq 2500 System identified multiple copies of TP53. Compared to human cells, elephant cells demonstrated increased apoptotic response following DNA damage, which could account for the low incidence of cancer (4.81%) in elephant populations.

Related Links
What elephants can teach scientists about fighting cancer in humans

How elephants avoid cancer

Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans Journal of the American Medical Association, DOI: 10.1001/jama.2015.13134

Friday, 11 March 2016

Ambry to share aggregated anonymous data from 10,000+ human exomes.

    • Exciting times.
      Firms are starting to be more open with the data they have collected for the benefit of mankind. But do watch out for the fine print. there's a disclaimer that although the data is 'free to download and use, the company retains copyright.'

    By Andrew Pollack
  • Posted March 08, 2016


Original post can be found here.
In an unusual move, a leading genetic testing company is making genetic information from the people it has tested publicly available, a move the company says could make a large trove of data available to researchers looking for genes linked to various diseases.
The company, Ambry Genetics, is expected to announce on Tuesday that it will put information from 10,000 of its customers into a database called AmbryShare.
“We’re going to discover a lot of new diagnostic targets and a lot of new drug targets,” Aaron Elliott, interim chief scientific officer at Ambry, which is based in Southern California, said in an interview. “With our volume, we can pull out a significant number of genes just by the sheer number we are looking at.”
The 10,000 people all have or have had breast or ovarian cancer and were tested by Ambry to see if they have genetic variants that increase the risk of those diseases. Ambry returned to the samples from those customers and, at its own expense, sequenced their exomes — the roughly 1.5 percent of a person’s genome that contains the recipes for the proteins produced by the body.
Since proteins perform most of the functions in the body, sequencing just that part of the genome provides considerable information, and is less expensive than sequencing the entire genome.
AmbryShare will not contain the actual exome of each person, because that would pose a risk to patient privacy. Rather it will contain aggregated data on the genetic variants.
For example, a researcher could look up how frequently a particular mutation occurs among the 10,000 people. Ones that occur frequently in these 10,000 patients, but not among healthy people, could raise the risk of developing those cancers.
Specialists welcomed Ambry’s move, but some said it was unclear how useful the information will be. The Exome Aggregation Consortium, an academic collaboration based at the Broad Institute of M.I.T. and Harvard, already has a similar publicly available database containing information from more than 60,000 exomes.
“It is not clear to me that 10,000 exomes changes the game much,” said David B. Goldstein, professor of genetics at Columbia University.
Ambry said its data would be from people with the diseases it tests for, like epilepsy and intellectual development problems, while the Broad database covers a more general population. Ambry said it hoped to add data from as many as 200,000 customers a year to the database.
The Ambry customers whose data is being used were not told specifically about this project. But in ordering tests they consent to having their samples used for research.
Various labs, including Ambry, have been pooling information on which mutations in certain known breast cancer risk genes are harmful or not. AmbryShare is different — aimed more at novel discoveries of genes linked to diseases.
Data can be valuable to drug companies. The consumer genetics company 23andMe sells access to data from its testing to drug makers and uses that data to develop drugs itself.
Charles Dunlop, founder and chief executive of Ambry, said he was approached by drug companies, but decided to make the company’s data freely available to expedite research.
“I’ve got Stage 4 cancer myself,” he said, referring to advanced prostate cancer that is in remission. “I don’t want to wait an extra day.”
He said Ambry had spent $20 million on the project. Ambry is privately held and majority-owned by Mr. Dunlop and his family, insulating it somewhat from shareholder pressure.

Correction: March 10, 2016 
An earlier version of this article described incorrectly the step that Ambry is taking with its customers’ data. It is making the data publicly available; it is not putting the data in the public domain. While the data is free to download and use, the company retains copyright.

Wednesday, 2 March 2016

Baylor releases Exome and WGS data of 7 cancer patients with Open Access

An open access pilot freely sharing cancer genomic data from participants in Texas
  • Scientific Data 3, Article number: 160010 (2016) 
  • ​doi:10.1038/sdata.2016.10
  •  In a pilot Open Access (OA) project from the CPRIT-funded Texas Cancer Research Biobank, many Texas cancer patients were willing to openly share genomic data from tumor and normal matched pair specimens. For the first time, genetic data from 7 human cancer cases with matched normal are freely available without requirement for data use agreements nor any major restriction except that end users cannot attempt to re-identify the participants (

There's whole exome seq data and 2 whole genome sequencing data where the sample quality is good enough for WGS.
A copy of the open-access TCRB data, conditions of use, and the HGSC’s Mercury informatics pipeline is available now for DNAnexus Platform users.

The full paper is here
A copy of the data is also available for DNAnexus Platform users here

Datanami, Woe be me