Scientists at deCODE genetics and academic colleagues from Iceland, China, Sweden, the UK and Australia today report the discovery of the most important single-letter variation (SNP) in the sequence of the human genome yet associated with risk of primary open-angle glaucoma. This is the most common form of glaucoma and a major cause of blindness worldwide.

The SNP on chromosome 7q31 is common among Europeans, with approximately 6% of people of European ancestry carrying two copies of the at-risk version, putting them at roughly 60% greater risk of developing the disease than those who carry none. But among Chinese, the impact of the SNP is markedy different. In study groups from Hong Kong and Shantou, the at-risk version of the SNP is shown to be carried by less than 1% the population, but each copy carried confers a more than five-fold increase in risk. The SNP is near the genes encoding caveolin 1 and 2, membrane proteins that are expressed in the meshwork that drains fluid from the eye, a process that if disturbed can increase pressure on the optic nerve and lead to glaucoma.

“The key to reducing the personal and public health impact of glaucoma is early diagnosis and treatment to slow the loss of sight. Discoveries such as today’s, which follows on our previous landmark findings in exfoliation glaucoma, are important because we can fold them directly into tests to target screening and to detect and treat more disease earlier. Moreover, among Chinese this latest SNP alone can define a small fraction of the population that should be very carefully screened. This underscores the value of being able to systematically analyze the impact of genetic risk factors across continental ancestries. Not only are these markers medically useful, they also tell us a bit about evolution and the spread of humanity across the globe,” said Kari Stefansson, deCODE’s Executive Chairman and President of Research and senior author of the study.

The authors would like to thank the more than 40,000 people who participated in this study, both glaucoma patients and control subjects. The paper, “Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma,” is published online in Nature Genetics at www.nature.com/ng and will appear in an upcoming print edition of the journal.

Primary open-angle glaucoma is a disease in which the optic nerve becomes damaged, leading to a progressive loss of sight. It affects tens of millions of people worldwide, mostly those over the age of 50. Incidence increases with age and varies between populations. Other known risk factors include high blood pressure and diabetes. Current treatments include eye drops that reduce pressure on the optic nerve, as well as surgery.

deCODE Discovers Second Common Genetic Risk Factor for Atrial Fibrillation and Stroke. Will be integrated into deCODE AF™ DNA-based risk assessment test, and into the deCODEme™ and deCODEme Cardio™ scans.

Scientists at deCODE genetics and colleagues from Europe and the United States today report the discovery of a common single-letter variant in the sequence of the human genome (SNP) conferring increased risk of atrial fibrillation (AF) and stroke. The findings will be integrated directly into the deCODE AF™ reference laboratory test for gauging individual risk of AF and stroke and helping to identify stroke patients who may benefit from enhanced monitoring for AF. The study is published online today in Nature Genetics.

The new SNP is in the ZFHX3 gene on chromosome 16q22, and the more than one third of people of European descent who carry one copy are at approximately 20% greater risk of AF and cardioembolic stroke than are individuals who carry none. AF is the most common type of cardiac arrhythmia, and is a major risk factor for stroke. Because AF is often intermittent and difficult to detect, gauging genetic susceptibility can help doctors to decide which of their stroke patients might benefit from longer-term monitoring for AF following a stroke. Those with stroke due to AF may be given different therapy than they would otherwise. This is the purpose of deCODE AF™, at the heart of which is the major AF and stroke variant discovered by deCODE on 4q25. Indeed today’s findings are the result of deCODE’s program to build on this work and to find new risk variants. After expanding their genome-wide association study in Iceland, the deCODE team took the top SNPs outside the 4q25 region and typed them in case-control cohorts from Iceland, Norway and the United States. This confirmed the ZFHX3 SNP as a risk variant for AF. Analysis in stroke cohorts from Iceland, Germany, Sweden and the UK demonstrated that this SNP was associated with increased risk of stroke, particularly cardioembolic stroke.

“This is an important discovery and all the more gratifying because we can integrate it straight into a test that is already helping to improve patient care in the clinic.
As with our 4q25 variant, this latest discovery has been replicated in numerous populations by us and others, and the connection to cardioembolic stroke is yet further evidence that we are putting our finger on an important pathway involved in AF and stroke risk. The ability to routinely test for these risk factors means that we can understand whom we should screen intensively for AF and then prescribe the drugs most suited to the cause of a particular patient’s disease. This is the sort of personalized medicine that genetics is enabling – individualized care that may mean not only better outcomes but significant potential savings to the healthcare system. Discoveries like this are the foundation upon which this transformation is being made,” said Kari Stefansson, CEO of deCODE.

deCODE and the authors wish to thank the participants who took part in this study and made it possible. Financial support for this study was provided by US National Institutes of Health grants HL075266 and U01 HL65962 and American Heart Association grant 0940116N; by the German Federal Ministry of Education and Research (01GI9909/3), by the German Migraine & Headache Society (DMKG), and by unrestricted grants of equal share from Astra Zeneca, Berlin Chemie, Boots Healthcare, Glaxo-Smith-Kline, McNeil Pharma, MSD Sharp & Dohme and Pfizer to the University of Muenster.