# Elucidation of Genetic Effects on Sleep and Circadian Traits

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $767,589

## Abstract

PROJECT SUMMARY
Sleep and circadian rhythms play critical roles in the maintenance of physical and mental health, with
disturbances in these domains associated with major public health consequences. Despite the abundance of
epidemiological evidence linking sleep and circadian traits to diverse pathologies, little is known about the
genetic factors that underlie these traits. Sleep and circadian traits, such as insomnia and chronotype, are
highly heritable and aggregate in families, suggesting a substantial proportion of risk is due to genetics.
Progress has been made in identifying risk variants for these traits using genome-wide association studies
(GWAS). However, GWAS results principally reside in non-coding regions of the genome and rarely pinpoint
the precise location of the actual effector genes. Mounting evidence is indicating that simply attributing GWAS
signals to the genes encoded in the closest genomic regions is not always accurate. As such, GWAS alone is
primarily beneficial to signal discovery, not functional gene discovery. The difficulty in elucidating the actual
effector genes for human GWAS signals is a significant barrier to identifying novel molecular regulators of
sleep. Despite wide-ranging tools utilizing model systems and in vitro approaches to conduct such functional
analyses, as well as computational methods to implicate causal variants, these approaches are underutilized in
the sleep and circadian domain. This proposal seeks to fill this critical knowledge gap by employing a team
science approach, bringing together expertise in the genomics of sleep and circadian rhythms that spans
humans, model systems, and computational biology, while simultaneously leveraging large existing datasets
for genetic discovery. In Aim 1, we will leverage existing biobank data for discovery of risk variants for insomnia
and chronotype. This will be followed, in Aim 2, by examination via a battery of spatial genomic analyses of
these loci using IPSC-derived neuro progenitor cells to identify causal variants. Finally, we will determine which
genes have functional relevance using Drosophila as a model system. Our global hypothesis is that genomic
variation is strongly associated with the behavioral manifestation of insomnia and chronotype and that our
cutting-edge molecular approaches will elucidate the causal variants and the corresponding effector genes at
these loci. We aim to translate genetic information into meaningful benefits for patient care by uncovering the
correct functional context of GWAS identified genomic variants involved in these traits and understanding how
they operate in this context.

## Key facts

- **NIH application ID:** 10216326
- **Project number:** 5R01HL143790-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Philip Richard Gehrman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $767,589
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216326

## Citation

> US National Institutes of Health, RePORTER application 10216326, Elucidation of Genetic Effects on Sleep and Circadian Traits (5R01HL143790-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10216326. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*