According to the New York Times, on December 10, 2012 the biotechnology giant, Amgen, said it was acquiring deCODE Genetics, a gene-hunting business known for its “headline grabbing discoveries linking genetic variations to disease. DeCODE, a privately held company in Iceland has studied the local population to identify genetic variations linked to schizophrenia, cancer and numerous other diseases.” Dr. Kari Stefanson, a neurologist who had taught at the University of Chicago and Harvard, realized that Iceland, his native country, would be an ideal place to perform studies in an attempt to detect genetic variants that raise or lower the risk of various diseases. “Iceland has good medical and genealogical records and a population that is not very diverse genetically.” The National Institutes of Dental and Craniofacial Research has awarded a grant to Dr. Jeffrey Gulcher of deCODE to investigate pain syndromes including TMD. We are extremely happy that the deCODE team has taken up the TMD challenge!
Abstract: This project proposes to generate new knowledge on the basic pathophysiology of chronic neuropathic pain by determining the genetic differences between patients who develop chronic neuropathic pain after initial tissue injury versus those who do not despite having the same acute tissue injury. The researchers will use the unique genetic resources gathered and developed at deCODE Genetics for whole genome sequence-based human pain genetics studies to uncover high risk variants of low frequency significantly associated to conversion from acute to chronic pain. The project will extensively re-phenotype large cohorts (groups of patients) with chronic neuropathic pain, including common forms of craniofacial pain. There are already over 12,000 Icelandic patients who have or are likely to have certain chronic neuropathic pain syndromes such as phantom tooth pain (persistent dento-alveolar pain (PDAP)), Temporomandibular Disorders (TMD), and post-mastectomy pain syndrome. The investigators will also screen a large cohort of Icelanders taking gabapentin or pregabalin for common chronic pain syndromes, including diabetic neuropathy and post-herpetic neuralgia. The extra phenotyping will give them additional dimensions beyond the basic pain symptomology on which to base the genetic analysis. It will also make it easier to replicate findings in outside pain cohorts that have already been well-phenotyped by their collaborators.
Although costs are dropping rapidly, it is still very expensive to fully sequence the genomes of the thousands of individuals that are required for well-powered disease association studies. These investigators can generate whole genome sequences for large cohorts of pain syndromes and controls in Iceland more quickly and cost-effectively than in other populations. By using their already existing genealogy database and high density DNA chip data they expect to find many new genetic associations that will increase our understanding of the conversion from acute to chronic neuropathic pain syndromes. The primary data generated in this grant will be made widely available for others to build on.