Scientists in the University of Miami Miller School of Medicine’s John P. Hussman Institute for Human Genomics have been awarded a five-year, $6.9 million grant from the National Institute on Aging to map how African and Amerindian DNA regulates its genes in human brain cells.
While similar regulatory “architecture” studies have been done for DNA of European ancestry, these studies have not been done for African or Amerindian ancestries. Studies have now shown that the genetic risk as well as protective genes for Alzheimer disease are different among ancestries. Thus, this knowledge is critical to understanding Alzheimer disease in both the African American and Latino/Hispanic populations, which has ancestors from both African, Amerindian and European origins.
Hussman Institute investigators, Jeffery M. Vance, M.D., Ph.D., professor of human genetics in the Dr. John T. Macdonald Foundation Department of Human Genetics and the Department of Neurology; Derek Dykxhoorn, Ph.D., research associate professor of human genetics; Juan Young, Ph.D., research associate professor of human genetics and Anthony Griswold, Ph.D., research assistant professor of human genetics are principle investigators for the grant entitled, “Functional Genomic Studies in Diverse Populations to Characterize Genetic Loci for Alzheimer's disease.”
They are supported by Hussman Institute co-investigators, Margaret A. Pericak-Vance, Ph.D., director of the John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Professor of Human Genetics and Professor of Neurology, and Executive Vice Chair, Dr. John T. Macdonald Foundation Department of Human Genetics, Brian Kunkle, M.P.H., Ph.D., research assistant professor in Human Genetics and Farid Rajabli, Ph.D., associate scientist, as well as colleagues at Case Western Reserve University and the University of Pennsylvania.
Genetic Role in AD
Currently 5.8 million people in the United States have Alzheimer disease, and as the population ages, cases are estimated to increase to 11-16 million in 2050 with 1 in 45 Americans affected. Genetics plays a major role in the risk to develop AD, and the genes driving this risk often differ between ancestries. As 98% of the human genome does not “code” for proteins, but is involved in regulating gene expression and interaction, it is not surprising that most AD risk variants lie in these regulatory regions and are the focus of this project.
The grant is part of a newly created functional genomics consortium funded by the National Institute on Aging for Alzheimer disease, as part of the larger international Alzheimer genetic research efforts. Other funded projects in the consortium were awarded to investigators at Columbia University, Stanford University, Yale University (Regenerative Research Foundation), Baylor University and Boston University. University of Miami Hussman Institute investigators believe the grant will help unlock some of the mysteries of AD,
"Each funded group of the consortium will investigate a different aspect of the functional genomics of Alzheimer disease," Dr. Jeffery Vance said. “The University of Miami grant will generate data in both African-American and Latino/Hispanic populations that will be applicable for Alzheimer disease as well as other genetic neurological diseases."
"This new grant and the consortium positions us among the premier academic research centers studying Alzheimer disease in the world and will enable us to leverage these collaborations to move closer to identifying therapeutic approaches that can help treat this increasingly pervasive disease,” Dr. Dykxhoorn said.
“If drug development for late-onset Alzheimer's disease continues to be based on data gathered primarily or exclusively from non-Hispanic Whites, the resulting therapies will, unavoidably, be tailored to benefit this specific subset of the world population,” Dr. Young said. “Thus, it is important to include diverse genomes as we move forward towards therapies.”
“Genetic studies have pinpointed more than 25 genetic variants associated with late-onset Alzheimer disease protection and/or risk in European ancestries, but very few studies to date have recruited a diverse group of participants that comes anywhere close to representing the unique tapestry of human genetics” said Dr. Pericak-Vance, director of the Hussman Institute. “This major grant adds to the broad portfolio of NIH support to the Hussman Institute’s genomics research program, adding to our No. 2 national ranking for NIH genetic research funding at the Miller School.”