# A Community Zebrafish Resource for Modeling GWAS Biology

> **NIH NIH R24** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $770,889

## Abstract

PROJECT SUMMARY:
Our proposal “Community Zebrafish Resource for Modeling GWAS Biology” applies novel approaches,
algorithms and methods developed within our consortium for functional analysis of human GWAS hits using
the zebrafish model system. Our consortium has accumulated broad experience in zebrafish genetics, genome
editing, bioinformatics, functional assay development, and human disease modeling as well as innovative
mechanistic studies to elucidate individual gene function. During the previous cycle of the award, we
established efficient high-content platforms for the functional analysis of coding sequence variation in zebrafish
to complement GWAS projects across a variety of complex human traits, and provided pathway entry points
and genetic models for understanding disease. In this renewal application, we extend our functional exploration
of single and/or multiple GWAS loci and their roles in biological networks underlying human medical traits to
include prevalent non-coding variation and drug responses through the following Specific Aims:
Aim 1-Functionally analyze loci from multiple GWAS studies on blood, liver, heart and vessel traits, optimizing
assay development and gene editing using CRISPR-Cas9 technology in zebrafish.
 a) Using validated assays we will examine the function of multiple coding genes in GWAS loci and
generate genetic models in the zebrafish using CRISPR-Cas9 technology.
 b) Accelerate in vivo gene function evaluation by optimization of genome editing in zebrafish using the
CRISPR-Cas9 technology.
Aim 2-Survey landscapes of genomic regulatory regions in different cell lineages in zebrafish and use the
information to support better mapping and functional evaluation of regulatory variants from GWAS loci.
 a) Using ATAC-seq, ChIP-seq, Methyl-seq, and companion RNA-seq analyses we will establish a
comprehensive database of conserved (orthologous) regulatory regions in different cell lineages and organs of
both zebrafish and human. We will define regulatory regions in different cell types at different developmental
stages which are important for cell lineage differentiation, maintenance and function in zebrafish.
 b) We will map regulatory effects from GWAS loci to conserved zebrafish regulatory regions and test
individual and/or multiple regulatory effects for their roles in specific GWAS traits using genome editing
technology and validated functional assays in zebrafish.
 c) Categorize conserved GWAS loci based on function and catalog genome editing reagents for
disease modeling and mechanistic studies and drug discovery.

## Key facts

- **NIH application ID:** 9988922
- **Project number:** 5R24OD017870-07
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Wolfram Goessling
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $770,889
- **Award type:** 5
- **Project period:** 2014-05-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988922

## Citation

> US National Institutes of Health, RePORTER application 9988922, A Community Zebrafish Resource for Modeling GWAS Biology (5R24OD017870-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9988922. Licensed CC0.

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