HGG Advances (Jul 2022)
The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish
- Michael D. Osterman,
- Yeunjoo E. Song,
- Larry D. Adams,
- Renee A. Laux,
- Laura J. Caywood,
- Michael B. Prough,
- Jason E. Clouse,
- Sharlene D. Herington,
- Susan H. Slifer,
- Audrey Lynn,
- M. Denise Fuzzell,
- Sarada L. Fuzzell,
- Sherri D. Hochstetler,
- Kristy Miskimen,
- Leighanne R. Main,
- Daniel A. Dorfsman,
- Paula Ogrocki,
- Alan J. Lerner,
- Jairo Ramos,
- Jeffery M. Vance,
- Michael L. Cuccaro,
- William K. Scott,
- Margaret A. Pericak-Vance,
- Jonathan L. Haines
Affiliations
- Michael D. Osterman
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Corresponding author
- Yeunjoo E. Song
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Larry D. Adams
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
- Renee A. Laux
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Laura J. Caywood
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
- Michael B. Prough
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
- Jason E. Clouse
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
- Sharlene D. Herington
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
- Susan H. Slifer
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
- Audrey Lynn
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- M. Denise Fuzzell
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Sarada L. Fuzzell
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Sherri D. Hochstetler
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Kristy Miskimen
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Leighanne R. Main
- Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Daniel A. Dorfsman
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA
- Paula Ogrocki
- Department of Neurology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Alan J. Lerner
- Department of Neurology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Jairo Ramos
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
- Jeffery M. Vance
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA
- Michael L. Cuccaro
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA
- William K. Scott
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA
- Margaret A. Pericak-Vance
- John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA
- Jonathan L. Haines
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Corresponding author
- Journal volume & issue
-
Vol. 3,
no. 3
p. 100114
Abstract
Summary: Alzheimer disease (AD) is the most common type of dementia and is currently estimated to affect 6.2 million Americans. It ranks as the sixth leading cause of death in the United States, and the proportion of deaths due to AD has been increasing since 2000, while the proportion of many other leading causes of deaths have decreased or remained constant. The risk for AD is multifactorial, including genetic and environmental risk factors. Although APOE ε4 remains the largest genetic risk factor for AD, more than 26 other loci have been associated with AD risk. Here, we recruited Amish adults from Ohio and Indiana to investigate AD risk and protective genetic effects. As a founder population that typically practices endogamy, variants that are rare in the general population may be of a higher frequency in the Amish population. Since the Amish have a slightly lower incidence and later age of onset of disease, they represent an excellent and unique population for research on protective genetic variants. We compared AD risk in the Amish and to a non-Amish population through APOE genotype, a non-APOE genetic risk score of genome-wide significant variants, and a non-APOE polygenic risk score considering all of the variants. Our results highlight the lesser relative impact of APOE and differing genetic architecture of AD risk in the Amish compared to a non-Amish, general European ancestry population.
