# From Obesity GWAS to therapeutic targets

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $702,522

## Abstract

Project Summary/Abstract
Obesity leads to an increased risk for type 2 diabetes, heart attack, many types of cancer, hypertension,
stroke, and is estimated to soon be the leading cause of death in the US. Through twin and family studies,
obesity has been found to have a 40-70% heritability rate, pointing to a strong genetic etiology. The long-term
objective of our studies is to determine how genetic variation predisposes humans to obesity and what the
therapeutic implications are for this condition.
To find common genetic variants associated with obesity, numerous genome-wide association studies (GWAS)
have been performed. Over 500 loci have been found to associate with increased body weight index (BMI), all
of which reside in noncoding regions of the genome . However, little progress has been made in outlining the
causal SNPs and understanding the mechanisms by which they actually cause obesity.
In this proposal, we explore the hypothesis that obesity-associated SNPs affect regulatory regions that are
active in neuronal sub-population implicated in the regulation of food intake and body weight.
Using state-of-the-art approaches that we have recently pioneered through collaborations between the Ahituv
and Vaisse laboratories we propose to:
- Extend and refine the regulatory landscape of hypothalamic neuronal subpopulations implicated in body
weight regulation to identify candidate regulatory elements overlapping obesity GWAS single nucleotide
polymorphisms (SNPs).
- Use CRISPR inactivation (CRISPRi) in mice to directly test the functional role of regulatory elements that
encompass obesity-associated SNPs.
- Use CRISPR activation (CRISPRa) in mice to test the therapeutic potential of activity modulation of identified
target regulatory regions.
Combined, our work will not only provide a regulatory map of neuronal subtypes associated obesity, but also
functionally characterize these regions and show their therapeutic potential.

## Key facts

- **NIH application ID:** 10200035
- **Project number:** 5R01DK124769-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nadav Ahituv
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $702,522
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200035

## Citation

> US National Institutes of Health, RePORTER application 10200035, From Obesity GWAS to therapeutic targets (5R01DK124769-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10200035. Licensed CC0.

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