Mind the IGAP—Transatlantic Consortium to Map AD Genes
The first human genome sequence came out—to much fanfare—10 years ago this month. Fitting that anniversary mode, then, is the launch yesterday of the International Genomics of Alzheimer’s Project (IGAP), an international collaboration that aims to pool genetic data amassed in Europe and North America to construct a detailed map of genetic variations that contribute to Alzheimer’s disease (AD). IGAP will draw on multiple genomewide association studies, pouring all their data into a “mega meta-analysis,” said Gerard Schellenberg, University of Pennsylvania School of Medicine, Philadelphia. Part of the payoff the scientists are hoping for will be better predictive power, Schellenberg added. “Right now we don’t have something to prevent Alzheimer’s, but if and when we do, genetic profiles will help determine who should be taking that approach,” he told ARF. “In the short term, identifying underlying genetics will give us insight into the mechanism of the disease.”
Schellenberg leads the Alzheimer’s Disease Genetics Consortium (ADGC) in the U.S., one of four groups that will pool data for IGAP. The others are: the European Alzheimer’s Disease Initiative (EADI) led by Phillipe Amouyel at the Institute Pasteur in Lille, France; The Genetic and Environmental Risk in Alzheimer’s Disease (GERAD) project in the U.K. led by Julie Williams at Cardiff University, Wales; and the neurology group of the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) led by Sudha Seshadri at Boston University, Massachusetts.
Together, the four groups have genetic samples from roughly 20,000 AD patients and 20,000 control subjects. IGAP correlates these sequences with data from the 1000 Genomes Project, which has cataloged the most detailed account of human genetic variation to date (see ARF related news story). The combination of large sample size and high-resolution human genetic mapping should allow IGAP to find rare genetic variants that predispose to AD. Studies typically find variants present in 5 percent or more of the population, said Schellenberg, but IGAP hopes to identify rarer variants that occur in as few as 1 percent of the population.
Schellenberg said he hopes initial results from the project will be presented this coming July at the International Conference on Alzheimer’s Disease in Paris, France. IGAP is supported by the Alzheimer’s Association in the U.S. and the Fondation Plan Alzheimer in France. Other funding is expected to come from government and nonprofit organizations that support the four groups, including the National Institute on Aging in the U.S. and the Medical Research Council in the U.K.
None of this new research would have been possible without the human genome project. To commemorate the tenth anniversary of that achievement, Science is publishing a series of short essays beginning this Friday and extending through February. The vignettes, from key leaders in the fields of biology, medicine, philosophy, and fine arts, will reflect on the impact that project has had on human endeavor.—Tom Fagan.
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