The 7^th annual The Genomics of Common Diseases conference is taking place this weekend, from September 7-10, in Keble College, Oxford University. At this conference, we seek to represent a top selection of the latest research characterizing the genetic basis of a range of common diseases.

We held the first Genomics of Common Diseases conference in 2007, with a program that highlighted rapid advancements in identifying common variants associated with a range of common diseases, made possible by new methods enabling genome-wide association studies (GWAS). Over the past seven years, our understanding of the genetic architecture of disease has been progressively redefined by GWAS characterizing common variation, the fine mapping of associated regions, the emergence and growth of new sequencing technologies and the assessment of rare variant association. We have represented the progress in the field facilitated by rapid improvements in and reduced costs of genotyping and sequencing technologies. We have also seen rapid growth in the scale of genetic datasets, with the need to analyze progressively larger sample sizes. Our sixth annual conference focused both on presenting the latest applied technologies and on how to meet challenges posed by the analysis and interpretation of these large-scale genetic datasets.

In developing our Genomics of Common Diseases program this year, we have emphasized the importance of moving from association to biological understanding. We continue to recognize the utility of a range of genetic technologies, and you will hear about the latest efforts involving large-scale studies using custom genotyping arrays, exome and whole-genome sequencing. However, instead of focusing on these different approaches, we have emphasized presentations and sessions that will allow us to discuss what we have learned about the genetic architecture and biological basis of a range of common diseases. We also stress the importance of the clinical translation of these results and a movement towards personalized medicine.

We are pleased to welcome three Keynote speakers this year to highlight areas we consider important to follow.  Sir David Weatherall will present an opening address on the population genetics and phenotypic diversity of the inherited haemoglobin disorders, as we consider how classical examples of monogenic disorders can inform on common diseases.  Wendy Bickmore will take a turn with studies demonstrating how 3-dimensional chromatin folding at long-range regulatory elements may allow for ‘remote control’ of distant enhancers.  Finally, Mel Greaves will provide a deeper look into cancer genomics, considering evidence for clonal evolution within cancer cell populations.

We also welcome 40 speakers who will present during 9 conference sessions, and over 100 poster presenters.

While we usually talk of moving from genetic discovery to translation, at GCD we will jump right in the first evening deep into clinical translation and pharmacogenetics. We are excited to hear from several leading examples of integrating genetic information into clinical settings, starting off with an overview by Mary Relling, who will also present on the impressive achievement at St. Jude’s of pre-emptive pharmacogenetic testing implemented to date for 4 genes and 11 drugs, all linked within the electronic medical record (EMR) and accompanied by clinical decision support materials.  Josh Peterson presents on the BioVU biobank at Vanderbilt University, which links to the EMR and integrates genetic and clinical factors, and on the Pharmacogenomic Resource for Enhanced Decisions in Care & Treatment (PREDICT) for genotyping of patients with high predicted risks.  Heidi Rehm plans to offer perspectives on assigning causality to variants and making interpreted genetic data readily available through a central database such as ClinVar, as well as on the reporting process they use in their own clinical genome service and GeneInsight.  Gert-Jan van Ommen will be uniting the EU, representing the Biobanking and BioMedical Resources Research Infrastructure (BBMRI) which aims to harmonize biobanks across Europe, including efforts within Genome of the Netherlands (GoNL).  Finally, Munir Pirmohamed will present on new studies using sequencing to analyze the genetic basis of adverse drug reactions (ADRs).

In our Genetic Discovery sessions, you will hear from latest efforts to use a combination of genotyping and sequencing approaches to characterize the genetic basis of particular common diseases or related traits.  Considerations include comparisons of different study designs (including population or family-based, sampling from extremes, and population isolates) as well as combinations of genotyping and sequencing approaches, and what sample sizes and methods may be needed for analysis of low-frequency and rare variation.  We will also consider ongoing questions on the genomic architecture and the relative contribution of rare variation to common diseases.

To complement the challenges faced in these genetic discovery efforts, we offer a statistical methods section that includes several new approaches.  These include multivariate methods to search for pleiotropy across related traits, to consider genetic and environmental interactions, and to analyze sequence datasets.

As a majority of GWAS-associated loci have been found within non-coding regions, we have also included a session on new approaches in characterization of regulatory variation. This includes high throughput functional assays, characterization of transcription factor binding sites and their conservation between organisms, and efforts to characterize regulatory code and apply this towards prediction.

We are also value lessons learned from studies in model organisms, and are looking forward to a new session examining genomic architecture and genotype to phenotype maps across model organisms from plants on up to cattle.

In order to make the most of our precious discussion time, our GCD participants have been asked to consider the following ‘Big Questions’ to guide our discussions.  (I only list here the first 5 of 10 questions; the remainder deal with broader forward looking questions which will be summarized later.)

1. What is the most important recent technological and/or analytical development for the genomics of common disease?
2. What are the primary challenges in seeking to better characterize the genetic basis and architecture of common disease?
3. What are the major limiting factors in moving from the identification of susceptibility loci to identifying the causal genes and functional variants for common disorders?
4. What are the primary challenges in clinical translation of these results and personalized medicine?
5. What is the clinical or biological value of documenting the whole genome sequence of an otherwise healthy child or young adult?

Please feel free to contribute to the discussion by sending your responses to these questions, and follow the conference on twitter at #GCD13.

— Orli Bahcall

Twitter: @obahcall