Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons.

Abstract

Poor sleep quality can have harmful health consequences. Although many aspects of sleep are heritable, the understandings of genetic factors involved in its physiology remain limited. Here, we performed a genome-wide association study (GWAS) using the Pittsburgh Sleep Quality Index (PSQI) in a multi-ethnic discovery cohort (n=2,868) and found two novel genome-wide loci on chromosomes 2 and 7 associated with global sleep quality. A meta-analysis in 12 independent cohorts (100,000 individuals) replicated the association on chromosome 7 between NPY and MPP6. While NPY is an important sleep gene, we tested for an independent functional role of MPP6. Expression data showed an association of this locus with both NPY and MPP6 mRNA levels in brain tissues. Moreover, knockdown of an orthologue of MPP6 in Drosophila melanogaster sleep center neurons resulted in decreased sleep duration. With convergent evidence, we describe a new locus impacting human variability in sleep quality through known NPY and novel MPP6 sleep genes.

Type

Journal article

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1093/sleep/zsaa211

Publication Info

Khoury, Samar, Qiao-Ping Wang, Marc Parisien, Pavel Gris, Andrey V Bortsov, Sarah D Linnstaedt, Samuel A McLean, Andrew S Tungate, et al. (2020). Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons. Sleep. 10.1093/sleep/zsaa211 Retrieved from https://hdl.handle.net/10161/21674.

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Scholars@Duke

Bortsov

Andrey V Bortsov

Assistant Professor in Anesthesiology

Dr. Andrey Bortsov is an Assistant Professor in the Department of Anesthesiology and holds a faculty position in the Center for Translational Pain Medicine (CTPM). He earned his Doctor of Medicine degree (1999) from Pavlov State Medical University, Saint Petersburg, Russia, and his PhD in Epidemiology (2010) from the University of South Carolina at Columbia.

In 2010, he joined the faculty at UNC Department of Anesthesiology as a Research Assistant Professor, where he studied genetics and non-genetic risk factors of chronic pain development after traumatic stressful events. Dr. Bortsov has published more than 30 peer-reviewed articles and presented his work at major and national and international conferences.

Dr. Bortsov joined the faulty at Duke University in 2016, where he continues his work on pain genomics. His major area of interest is application of novel computational and statistical methods to big genomic datasets to develop prediction models for disease risk and treatment outcomes. 

Nackley

Andrea Gail Nackley

Associate Professor in Anesthesiology

Pain is a multidimensional sensory and emotional experience that is important for our survival, but once pain becomes chronic it is no longer beneficial and, instead, becomes a disorder in and of itself. Chronic pain remains one of our nation’s most significant healthcare problems due to a limited understanding of the underlying genetic and environmental factors. There are three main objectives of our lab’s research in this area: 

  1. To determine the factors that put some people, but not others, at risk for maladaptive chronic pain conditions. To achieve this objective, we study genetic, biological, and environmental factors associated with the initial onset of pain as well as its severity and duration. In addition, we are beginning to study factors associated with patient-centered outcomes, which may have the power to predict optimal management strategies for different individuals.
  2. To elucidate the mechanism(s) whereby genetic, biological, and environmental factors drive chronic pain. To achieve this objective, we integrate molecular genetics, animal models, and clinical epidemiologic measures in order to reveal pathogenic processes that are unique to as well as common across a particular condition or individual(s). This line of inquiry will provide novel targets for the development of individualized therapeutics for the management of chronic pain.
  3. To improve pharmacologic management of pain. To achieve this objective, we conduct pre-clinical studies to test the efficacy of new compounds and to optimize the efficacy of existing compounds in patient-relevant animal models.

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