# Beyond PheWAS: Recognition of Phenotype Patterns for Discovery and Translation - Administrative Supplement

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $175,000

## Abstract

Project Summary
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 clinical understanding of risks and mechanisms for many diseases and conditions and
that may ultimately guide diagnosis and therapy on a patient-specific basis. The previous two
cycles of this effort (2011-2014 and 2014-2018) introduced the phenome-wide association study
(PheWAS) as a systematic and efficient approach to identify novel disease-variant associations
and discover pleiotropy using electronic health records (EHRs). This proposal will develop novel
methods to identify associations based on patterns of phenotypes using a phenotype risk score
(PheRS) methodology to systematically search for the influence of Mendelian disease variants
on common disease. By doing so, it also creates a way to assess pathogenicity for rare variants,
and will identify patients at highest risk of having undiagnosed Mendelian disease. The project is
enabled by large DNA biobanks coupled to de-identified copies of EHR. This project has four
specific aims. First, we will develop and validate PheRS for assessment of variant pathogenicity
by leveraging billing codes, laboratory data, and NLP features in its predictive algorithms. The
second aim is to apply PheRS in huge populations to create a robust repository of rare variant
associations in diverse populations (eMERGE Network and large national cohorts, which could
approach 2 million people with genotype data). The third aim is to assess Mendelian disease
penetrance and evaluate PheRS as a tool to identify patients at risk for undiagnosed Mendelian
disease. The fourth aim is make these tools and resources broadly available to aid in variant
interpretation and facilitate others running PheRS. The tools generated from this project will
validate new approaches to interpreting the function of rare variants, improve basic
understanding of Mendelian disease, greatly enhance our understanding of the contribution of
Mendelian disease variants to common disease and traits, and offers a potential approach to
identify subpopulations of patients for whom new therapies may offer benefit.

## Key facts

- **NIH application ID:** 10147537
- **Project number:** 3R01LM010685-11S1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Lisa Bastarache
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $175,000
- **Award type:** 3
- **Project period:** 2011-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147537

## Citation

> US National Institutes of Health, RePORTER application 10147537, Beyond PheWAS: Recognition of Phenotype Patterns for Discovery and Translation - Administrative Supplement (3R01LM010685-11S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10147537. Licensed CC0.

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