We are pleased publish today a Focus issue on cancer risk, including findings from the COGS (Collaborative Oncological Gene-environment Study) consortium, published as 13 coordinated papers in this Nature Genetics iCOGS collection.
At Nature Genetics, we give voice to leading efforts to understand the genetic basis of disease. Over the past six years, we have seen mass surveys of genetic variants across the human genome, called genome-wide association studies, yield key insights into hundreds of common diseases.
Today, we’re proud to see how COGS, extending this approach to oncology, has doubled the number of genetic regions implicated in breast, ovarian and prostate cancers. As such, these 13 papers represent a milestone in our understanding of these common cancers, and exemplify what’s needed in such discovery efforts.
To provide a brief summary before you dive in, several overall findings from this collection bear highlighting:
1) This collection implicates 74 new genomic regions in these 3 cancers, doubling the number of reported associations.
2) This work finds substantial contribution from common genetic variation to cancer risk heritability, explaining up to roughly 1/3 of the familial relative risk for these cancers.
3) The studies find that variation in some parts of our genomes is associated with multiple hormone-sensitive cancers, suggesting shared mechanisms.
4) This collection also establishes a general framework for refining initial association findings through fine-mapping and functional annotation.
5) Finally, these efforts have pointed to ways that such findings may find use in personal healthcare and genetic risk prediction.
These studies also exemplify what’s needed in such genetic discovery efforts, including these three important factors:
1) This work requires very large samples, with these new papers summarizing data from more than 200,000 people, making this the largest cancer genotyping discovery effort.
2) These studies entail collaboration, here bringing together researchers from more than 160 institutions worldwide, in four cancer-specific consortia, to execute over 40 studies.
3) This collection of studies pool efforts across distinct but related diseases – here, 3 hormone-related cancers. This allows more efficient use of hard won data, for faster and more precise insights into the shared versus unique genetic underpinnings of particular diseases.
In supporting this collaborative effort, we were pleased to work directly with the COGS authors to coordinate these 13 publications across 5 leading journals, working with editors at The American Journal of Human Genetics, Human Molecular Genetics, Nature Communications, and PLoS Genetics.
And, to best convey the findings, Nature Genetics is debuting a new online publishing format that builds from the single paper as unit of publication, to a broad, unified view into the entire iCOGS collection.
We hope that this iCOGS explorer microsite will help our readers quickly understand and access materials across the set of coordinated papers. This iCOGS explorer includes a series of essays, called Primers, which interactively guide readers through the studies, summarizing the main findings and themes of the collection, offering direct glimpses into each paper, and perspectives on how they relate to other work in the field.
This new online publishing format builds on the Threads used in the ENCODE explorer. These Primers now interlace “threads” (direct quotes from papers) with editorial analysis in order to provide more context and additional analysis.
We also hope that this provides an example to help the public understand current efforts to characterize the genetic basis of common diseases, as we review here how and why such studies are performed, and what insights are possible.
Without further delay, we welcome you to jump right into the Nature Genetics iCOGS collection. Not sure where to start or overwhelmed with this stack of materials? I recommend picking your favorite from these questions below, linked to answers in our Primers.
- How many new susceptibility loci were identified for each cancer? How does this add to the current literature?
- Were there genomic regions that included variants associated with more than one of these cancers? (Hint: Yes!) See shared susceptibility regions.
- How much of the heritability is explained by total (currently known) set of susceptibility loci for each of these cancers? See heritability esimates.
- What fine mapping efforts were included in the COGS studies?
- What is the COGS project? What is a mega-consortium?
- How was the Illumina custom genotyping iCOGS array designed? How did this prove useful in the current iCOGS collection?
- What are COGS plans for developing a next generation cross cancer array?
We hope that you find this collection and the iCOGS explorer useful, and that this proves of benefit in accessing the information in these current studies, as well as promoting continuing collaborative research.
Orli G. Bahcall Senior Editor Nature Genetics Twitter: @obahcall