# An Atlas of Clinical Associations mapping to Variants within Protein Structures

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $293,140

## Abstract

The fields of genomics and genetic epidemiology are undergoing a transformation due to two key advances:
next-generation sequencing technologies and biobanks linked to electronic health records. Both these advances
have led to new analytical methodologies; phenome-wide association studies that examine the impact of a
genetic variant for hundreds of human phenotypes, and statistical tests that group low-frequency variants for
association analyses. The current approach for grouping low-frequency variants is to consider a gene as the
functional unit tested, which is counter to decades of research indicating that proteins and protein complexes
are the true functional units of biology.
In this project, we fuse these ideas to generate tools and analyses of ~150,000 whole-exome sequences using
protein structural information from the Protein Data Bank. By performing a phenome-wide association study of
low-frequency genetic variants within specific protein regions, we will construct an online atlas of functional
protein regions mapped onto the clinical traits they impact.

## Key facts

- **NIH application ID:** 9964851
- **Project number:** 5R01GM126249-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** William S Bush
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,140
- **Award type:** 5
- **Project period:** 2018-09-30 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964851

## Citation

> US National Institutes of Health, RePORTER application 9964851, An Atlas of Clinical Associations mapping to Variants within Protein Structures (5R01GM126249-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9964851. Licensed CC0.

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