Genomic medicine offers hope for improved diagnostic methods and for more effective, patient-specific therapies. Genome-wide associated studies (GWAS) elucidate genetic markers that improve understanding of risks and causes for many diseases, and may guide diagnosis and therapy on a patient-specific basis. This project will take another approach to identify gene-disease associations: perform "reverse GWAS," or phenome- wide association study (PheWAS), to determine which phenotypes are associated with a given genotype. The project is enabled by a large DNA biobank coupled to a de- identified copy of the electronic medical record. This project has four specific aims. First, the project will develop and validate a standardized approach to extract disease phenotypes from EMR records, integrating national standard terminologies of clinical disorders and descriptors relating to treatment and diagnosis of each disease to create a sharable knowledge base. The project will use natural language processing, structured data queries, and heuristic and machine learning methods to accurately identify patients with each disease and corresponding controls.
The second aim i s to perform PheWAS analyses using existing genotype data. To validate the method, the project will use PheWAS to "rediscover" SNPs with known disease associations. The project will also investigate statistical methods for large-scale multiple hypothesis testing to discover novel phenotype associations.
The third aim i s to apply the PheWAS algorithms in four other sites with EMR-linked DNA biobanks and compare results. In the fourth aim, the project will validate novel phenotype-genotype associations discovered through PheWAS with new genotyping in a previously untested population. The tools generated from this project will not only make PheWAS possible, but will also broadly enable clinical research and subsequent genetic studies.

Public Health Relevance

The promise of genomic medicine is to predict individuals'disease risk and treatment given their genetic information. This project will develop methods to identify diseases from electronic medical records and then find novel genetic associations from existing genomic data.

Agency
National Institute of Health (NIH)
Institute
National Library of Medicine (NLM)
Type
Research Project (R01)
Project #
5R01LM010685-03
Application #
8528722
Study Section
Biomedical Library and Informatics Review Committee (BLR)
Program Officer
Ye, Jane
Project Start
2011-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$305,913
Indirect Cost
$109,815
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Shameer, Khader; Denny, Joshua C; Ding, Keyue et al. (2014) A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects. Hum Genet 133:95-109
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