Recent large-scale whole exome sequencing studies have identified protein function-altering variants occurring at low allele frequency in populations, for which the health impact is unknown. Our ongoing investigation of exonic variation in American Indians using whole exome sequencing has uncovered single nucleotide variants and small indels with predicted protein-altering function, which were genotyped in 1,127 Strong Heart Family Study participants. The main goal of this application is to assess the clinical and biological consequences of these variants for phenotypes relevant to heart and blood diseases. We will use the existing comprehensive phenotypic data on clinical assessments and biomarkers obtained in two clinical visits and the surveillance data on cardiovascular disease events to perform phenome-wide association analyses. The family data will allow mapping individuals with these variants in pedigrees to better understand their phenotypic correlations. This proposal addresses important gaps in our knowledge of the clinical phenotypes associated with rare protein function-altering variants in humans, which may have implications for precision medicine.

Public Health Relevance

This project will leverage existing genotypes and the extensive clinical and biomarker data in a population- based family study of American Indians to better understand the clinical implications of rare protein function- altering variants in populations. Findings from this study may have implications for precision medicine.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL140385-01
Application #
9440833
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Minear, Mollie A
Project Start
2017-09-15
Project End
2019-08-31
Budget Start
2017-09-15
Budget End
2018-08-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Franceschini, Nora; Frick, Amber; Kopp, Jeffrey B (2018) Genetic Testing in Clinical Settings. Am J Kidney Dis 72:569-581
Franceschini, Nora; Giambartolomei, Claudia; de Vries, Paul S et al. (2018) GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. Nat Commun 9:5141