HapMap brings focus to blindness study

Macular degeneration.
Macular degeneration
Image courtesy of National Eye Institute, NIH

Using the data provided by HapMap, a team of scientists at Harvard Medical School and the Broad Institute has discovered a new genetic variant associated with age-related macular degeneration (AMD), the leading cause of blindness in people over 60 years of age, as well as confirming previously reported variants. They estimate that genotypes related to just five variants in three different genes can explain fifty percent of the risk of developing AMD. These findings are published online in the journal Nature Genetics, and have implications for genetic research beyond AMD.

The new genetic common variant identified was found in a noncoding region of the Complement Factor H (CFH) gene, other variants of which were recently shown to be associated with the risk of developing AMD. In addition to CFH on chromosome 1, the scientists found that there was additive risk from alleles at the complement factor B (BF) and complement component 2 (C2) genes on chromosome 6, and the LOC gene on chromosome 10. Analyses of these findings demonstrate that five variants in these three genes explain about half the sibling risk of AMD in the study population (2,172 unrelated European-descended individuals 60 years of age or older, 1,238 affected individuals and 934 controls). Interestingly, these three genes do not appear to interact directly, but instead contribute to the risk of AMD independently.

Another interesting aspect of this study is not related to AMD directly but rather to the field of human genetics. The data provided in the Nature Genetics paper strongly suggest that common genetic variations, whether within coding regions of genes or not, can significantly influence the risk of developing common diseases, even for late-onset diseases such as AMD. This hypothesis needs to be tested with other large clinical cohorts in other common diseases.

The scientific team included principal investigator, Johanna M. Seddon of the Massachusetts Eye and Ear Infirmary (MEEI) and Harvard Medical School, lead author Julian Maller from Massachusetts General Hospital (MGH), Sarah George from MEEI, and Shaun Purcell, Jes Fagerness, David Altshuler and Mark Daly from MGH and the Broad Institute.