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BETHESDA, Md.—A massive project to study the genetic underpinnings of Alzheimer’s disease is being pushed forward by a new round of grants from the National Institutes of Health (NIH). Scientists at eight academic medical centers will use the new funding to analyze how some genomic sequences contribute to increased risk and others provide protection against the disease. The grants, expected to total $24 million over four years, will enable researchers to use sophisticated new technologies and computational methods for their analysis.
The research will be the latest phase of the Alzheimer’s Disease Sequencing Project (ADSP), a collaboration between the National Institute on Aging (NIA) and the National Human Genome Research Institute (NHGRI) that began in 2012. “The data-collection phase of the project is nearly complete and now that data needs to be analyzed,” Jean Zenklusen, director of NIH’s The Cancer Genome Atlas (TCGA) program, tells DDNews—TCGA, like the ADSP, is closely connected with NHGRI’s Large-Scale Genome Sequencing and Analysis Centers. “The next phase, which is now being funded, involves trying to understand the association between the variants and phenotypes that have been identified—both those that increase risk and those that appear to be protective.”
ADSP is a core component of the National Plan to Address Alzheimer’s Disease that was launched by the U.S. Department of Health and Human Services in 2012 under the umbrella of the National Alzheimer’s Project Act. The plan’s primary research goal is to create methods of preventing and effectively treat Alzheimer’s disease by 2025.
The first phase of the project determined the order of all 3 billion letters in the individual genomes of 580 participants. It also generated whole- exome sequencing data of an additional 11,000 volunteers—6,000 with Alzheimer’s compared to 5,000 without the disease. Funds supporting the new analysis come from recent additions to the NIA budget that were intended to be used for Alzheimer’s research.
The primary aim of the research teams receiving grants will be to use data generated by ADSP to identify rare genetic variants that protect against or contribute to Alzheimer’s disease. Additionally, they will explore differences in data from different racial and ethnic groups, and examine how brain images and other biomarkers are associated with genome sequences.
“By looking at the genomic sequencing, scientists may be able to learn a great deal about the genes and the biological pathways that are involved in the disease and gain rapid insight into what’s going on at the molecular level,” says Zenklusen. “In some cases, researchers may also get lucky and find protective alleles that can provide more effective therapeutic targets.”
The largest of the grants being awarded will go to a five- university collaboration called the Consortium for Alzheimer’s Sequence Analysis (CASA). The consortium is receiving a $12.6-million grant to analyze ADSP sequence data generated from 6,000 volunteers with Alzheimer’s disease and 5,000 older participants free of the disorder. Researchers with CASA will also study genomic data from 111 large families, some of Caribbean Hispanic descent, that include multiple members with Alzheimer’s disease. Their goal is to identify rare genetic variants that protect against or cause Alzheimer’s disease.
The second- largest grant will be directed to Dr. Eric Boerwinkle of the University of Texas Health Sciences Center, who is focused on identifying in ADSP datasets the number of copies of a particular gene or region of the genome that varies from one individual to the next. He will attempt to understand how these variations are associated with risk or protection from Alzheimer’s. Researchers working with Boerwinkle will use sophisticated bioinformatics and computational tools to explore the function of genes that are disrupted or overlapped by gene copies and how they may impact disease risk in multiple ethnic and racial groups. They will also examine whether these copies influence memory performance, brain images and other biomarkers of Alzheimer’s disease.
Medical centers at the following academic institutions also received grants: University of Pennsylvania, Case Western Reserve University, University of Miami, Columbia University, Boston University, University of Washington and Washington University in St. Louis.
Researchers receiving grants will collaborate with the NHGRI’s Large-Scale Genome Sequencing and Analysis Centers program, an NIH-supported consortium that generates and analyzes large genome sequence datasets for biomedical research projects.
“The ADSP data generated over the last two years are now paving the way for cutting-edge investigations that may lead to new targets for drug development,” said NHGRI Director Eric D. Green. “The upcoming data analyses will be pivotal for realizing that vision.”