The goal of this """"""""Grand Opportunities"""""""" project is to create a unique and comprehensive population-based resource for research into the genetic and environmental basis of common age-related diseases and their treatment, and factors influencing healthy aging and longevity. The proposed resource will bring together into a broadly accessible database, an extraordinarily rich set of data on 100,000 participants in the Research Program on Genes, Environment and Health (RPGEH), based in the Kaiser Permanente Medical Care Plan in Northern California (KPNC). The RPGEH includes data from the comprehensive, longitudinal electronic medical records of KPNC;a participant questionnaire with demographic, behavioral, and other risk factor data;a geographic information system (GIS) database that maps environmental exposures (e.g., air and water quality) and neighborhood characteristics to participants'residential histories;and saliva samples obtained from all participants using Oragene kits. The 100,000 completed participants in RPGEH have broadly consented to have their DNA and other data used to conduct studies of genetic and environmental influences on health and disease. The average age of the subjects is 65 years, with good representation of all the major ethnic groups. In this proposal, we are specifically requesting funds to add valuable genome-wide association data for 700,000 SNPs and measures of telomere length to the resource using a novel Affymetrix GeneTitan genotyping system, to enable comprehensive studies of genetic and environmental factors that influence the risk of adult-onset diseases and their treatment, and healthy aging. The selection of SNPs will be customized to facilitate the detection of new associations and to follow up previously identified associations. The longitudinal nature of the electronic clinical records maintained by KPNC means that the phenotype data subject to analysis can be used to address questions of health and disease over time. We anticipate that this resource will serve the needs of a vast array of researchers both nationally and internationally to investigate complex questions regarding aging, both for the short term and for years to come.

Public Health Relevance

The goal of this """"""""Grand Opportunities"""""""" project is to create a unique and comprehensive population-based resource for research into the genetic and environmental basis of common age-related diseases and their treatment, and factors influencing healthy aging and longevity. The proposed resource will bring together into a broadly accessible database, an extraordinarily rich set of data on 100,000 participants. The proposed project will add genetic data on 700,000 SNPs and data on telomere length to data from comprehensive electronic health records;a participant questionnaire with demographic, behavioral, and other risk factor data;a geographic information system (GIS) database that maps environmental exposures to participants'residential histories.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
High Impact Research and Research Infrastructure Programs (RC2)
Project #
1RC2AG036607-01
Application #
7853270
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (O5))
Program Officer
Slater, Stanley L
Project Start
2009-09-30
Project End
2011-08-31
Budget Start
2009-09-30
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$12,750,193
Indirect Cost
Name
Kaiser Foundation Research Institute
Department
Type
DUNS #
150829349
City
Oakland
State
CA
Country
United States
Zip Code
94612
Hoffmann, Thomas J; Choquet, Hélène; Yin, Jie et al. (2018) A Large Multiethnic Genome-Wide Association Study of Adult Body Mass Index Identifies Novel Loci. Genetics 210:499-515
Oni-Orisan, Akinyemi; Hoffmann, Thomas J; Ranatunga, Dilrini et al. (2018) Characterization of Statin Low-Density Lipoprotein Cholesterol Dose-Response Using Electronic Health Records in a Large Population-Based Cohort. Circ Genom Precis Med 11:e002043
Choquet, Hélène; Paylakhi, Seyyedhassan; Kneeland, Stephen C et al. (2018) A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci. Nat Commun 9:2278
Ioannidis, Nilah M; Wang, Wei; Furlotte, Nicholas A et al. (2018) Gene expression imputation identifies candidate genes and susceptibility loci associated with cutaneous squamous cell carcinoma. Nat Commun 9:4264
Hoffmann, Thomas J; Theusch, Elizabeth; Haldar, Tanushree et al. (2018) A large electronic-health-record-based genome-wide study of serum lipids. Nat Genet 50:401-413
Jorgenson, Eric; Matharu, Navneet; Palmer, Melody R et al. (2018) Genetic variation in the SIM1 locus is associated with erectile dysfunction. Proc Natl Acad Sci U S A 115:11018-11023
Choquet, Hélène; Thai, Khanh K; Yin, Jie et al. (2017) A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure. Nat Commun 8:2108
Kim, Stuart K; Kleimeyer, John P; Ahmed, Marwa A et al. (2017) Two genetic loci associated with ankle injury. PLoS One 12:e0185355
Gianfrancesco, Milena A; Glymour, M Maria; Walter, Stefan et al. (2017) Causal Effect of Genetic Variants Associated With Body Mass Index on Multiple Sclerosis Susceptibility. Am J Epidemiol 185:162-171
Dujic, T; Zhou, K; Yee, S W et al. (2017) Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis. Clin Pharmacol Ther 101:763-772

Showing the most recent 10 out of 30 publications