# Single cell atlas as a roadmap for interpreting human genetic variation in complex disease

> **NIH NIH F32** · BROAD INSTITUTE, INC. · 2021 · $66,390

## Abstract

Project Summary
Genome wide association studies (GWAS) have successfully identified thousands of loci likely affecting human
health. To translate these findings into therapeutic targets and disease treatments, we need to understand the
cellular context and underlying biological mechanisms through which each disease associated variant disrupts
function. Large scale, information rich datasets are being generated across multiple modalities including
transcriptomics from single cell RNA-seq studies, traits and phenotypes from the UK Biobank and germline
genetic variation from exome sequencing studies. Here, we propose to develop methods to integrate these
amazing resources towards understanding the identifying biological and cellular mechanisms that are leading
to disease. The objectives will be accomplished with the following specific aims:
1) Integrate population scale biological datasets including UK Biobank and single cell transcriptomics data to
construct gene modules with the goal to recapitulate biological pathways.
2) Develop a statistical framework to measure mutational burden across each of the cell type specific gene
modules. Together, this research proposal will increase the power in interpreting human genetic variation and
help better understand the mechanism through which they act.
These methods are being developed around an IBD dataset and will derive substantial molecular information
about the mechanisms driving IBD. The lessons and methodological advances from this work will be directly
applicable in many complex disease contexts.

## Key facts

- **NIH application ID:** 10179368
- **Project number:** 5F32HG011434-02
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Karthik Anand Jagadeesh
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179368

## Citation

> US National Institutes of Health, RePORTER application 10179368, Single cell atlas as a roadmap for interpreting human genetic variation in complex disease (5F32HG011434-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10179368. Licensed CC0.

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