Advances in molecular and statistical methods have greatly facilitated the identification of susceptibility genes for diseases, such as Alzheimer disease, that are common in older adults. These same methods may be applied to the study of the natural aging process to identify genes that are associated with a long and healthy life. Identification of both disease-causing and health-promoting polymorphisms and their interactions with the environment has the potential to greatly improve the health of older adults, the most rapidly growing segment of the U.S. population. One method of identifying genes associated with a particular trait is to study relatively stable, isolated populations established by a few founding members, such as the Amish community in northern Indiana. This community has previously participated in a cross-sectional survey for cognitive impairment conducted from 1991-1993. Several families with multiple cognitively impaired individuals were identified and included in ongoing studies of the genetics of dementia at the DUMC Center for Human Genetics. We also observed in these families apparent clustering of """"""""successful aging"""""""", suggesting that this trait may be, in part, under genetic control. In light of these observations, we propose a second population survey to systematically evaluate Amish adults aged 80 and older for cognitive and functional impairment. We will determine the prevalence and degree of familial aggregation of successful aging in the Amish community and perform genetic studies to identify genes associated with successful aging. To accomplish these goals, we specifically propose to: (1) conduct a community survey of Amish residents aged 80 and older in Adams and surrounding counties in Indiana and Holmes and surrounding counties in Ohio; (2) examine the relationship between successful aging and genes implicated in longevity; (3) perform a complete genomic screen for successful aging loci, and (4) follow-up results of the genomic screen through positional cloning and candidate gene analysis approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG019726-01A2
Application #
6613193
Study Section
Special Emphasis Panel (ZRG1-EDC-3 (01))
Program Officer
Chon-Lee, Angie J
Project Start
2003-07-01
Project End
2008-04-30
Budget Start
2003-07-01
Budget End
2004-04-30
Support Year
1
Fiscal Year
2003
Total Cost
$568,358
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Hou, Liping; Kember, Rachel L; Roach, Jared C et al. (2017) A population-specific reference panel empowers genetic studies of Anabaptist populations. Sci Rep 7:6079
Hoffman, Joshua D; van Grinsven, Mark J J P; Li, Chun et al. (2016) Genetic Association Analysis of Drusen Progression. Invest Ophthalmol Vis Sci 57:2225-31
D'Aoust, Laura N; Cummings, Anna C; Laux, Renee et al. (2015) Examination of candidate exonic variants for association to Alzheimer disease in the Amish. PLoS One 10:e0118043
Hoffman, Joshua D; Cooke Bailey, Jessica N; D'Aoust, Laura et al. (2014) Rare complement factor H variant associated with age-related macular degeneration in the Amish. Invest Ophthalmol Vis Sci 55:4455-60
Crawford, Dana C; Dumitrescu, Logan; Goodloe, Robert et al. (2014) Rare variant APOC3 R19X is associated with cardio-protective profiles in a diverse population-based survey as part of the Epidemiologic Architecture for Genes Linked to Environment Study. Circ Cardiovasc Genet 7:848-53
Davis, M F; Cummings, A C; D'Aoust, L N et al. (2013) Parkinson disease loci in the mid-western Amish. Hum Genet 132:1213-21
Cummings, Anna C; Torstenson, Eric; Davis, Mary F et al. (2013) Evaluating power and type 1 error in large pedigree analyses of binary traits. PLoS One 8:e62615
Edwards, Digna R Velez; Gilbert, John R; Hicks, James E et al. (2013) Linkage and association of successful aging to the 6q25 region in large Amish kindreds. Age (Dordr) 35:1467-77
Courtenay, Monique D; Gilbert, John R; Jiang, Lan et al. (2012) Mitochondrial haplogroup X is associated with successful aging in the Amish. Hum Genet 131:201-8
Cummings, Anna C; Jiang, Lan; Velez Edwards, Digna R et al. (2012) Genome-wide association and linkage study in the Amish detects a novel candidate late-onset Alzheimer disease gene. Ann Hum Genet 76:342-51

Showing the most recent 10 out of 17 publications