# Genetics of chronotype and impact on metabolic disease

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $427,500

## Abstract

Dys-regulation of the body's internal circadian time-keeping mechanism is an
established risk factor for metabolic disease. Chronotype, or sleep-timing preference
during the 24 hour day, is a behavioral manifestation of underlying circadian rhythms
that can be assessed by questionnaires in large populations. Chronotype is heritable
and from large-scale GWAS, robust underlying genetic variants implicating circadian and
other pathways have been found, providing opportunities to understand the biological
causes and consequences of circadian rhythm disturbances on human physiology. We
hypothesize that identification of causal variants underlying genetic associations,
characterization of the molecular, cellular and physiologic function of culprit mutations
and genes, and dissection of causal genetic relationships between chronotype variants
and metabolic disease using computational and experimental approaches will help
illuminate the role of chronotype in health, obesity and risk of type 2 diabetes. In order
to test these hypotheses, we propose the following specific aims: 1) To identify causal
variants underlying known genome-wide significant and newly discovered chronotype
loci using large publicly available genotype and self-reported chronotype (n~500k) and
objective sleep timing information (n~100k); 2) To determine the molecular, cellular and
physiologic effects of causal variants and genes in human models using analyses of
existing resources, experimental assays and unique controlled in-laboratory sample
collections; and 3) To systematically evaluate the polygenic overlap of chronotype genes
and pathways with type 2 diabetes susceptibility. This work will build the knowledge
necessary to understand the mechanistic link of timing of the internal circadian rhythm to
type 2 diabetes, opening potential new avenues of treatment for circadian rhythm
disorders and type 2 diabetes.

## Key facts

- **NIH application ID:** 9938547
- **Project number:** 5R01DK107859-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** RICHA SAXENA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,500
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938547

## Citation

> US National Institutes of Health, RePORTER application 9938547, Genetics of chronotype and impact on metabolic disease (5R01DK107859-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9938547. Licensed CC0.

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