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.

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.
Smith

Shad Benjamin Smith

Associate Professor of Anesthesiology

Dr. Shad Smith is an assistant professor in the Department of Anesthesiology and holds a faculty position in the Center for Translational Pain Medicine (CTPM). Dr. Smith also has an adjunct appointment at the University of North Carolina at Chapel Hill, as part of the Center for Pain Research and Innovation (CPRI). He earned his bachelor’s degree in psychology with minors in chemistry and zoology from Brigham Young University, before moving on to graduate school.

In 2006, he graduated with a doctorate in psychology with an emphasis in behavioral neuroscience. Following his time at McGill, Dr. Smith accepted a post-doctoral fellowship in the CPRI at the UNC School of Dentistry. He received a Ruth L. Kirschstein National Research Service Award in 2008 to study the role of alpha adrenergic mechanisms in chronic orofacial pain. He joined the faculty at UNC as a research assistant professor in 2011. Dr. Smith has also served since 2007 as a research consultant, and since 2010 as the Director of Bioinformatics, for Algynomics, Inc., a Chapel Hill-based biotech firm spun off from research activities within the UNC School of Dentistry.

Dr. Smith joined the faculty at Duke University in 2016, where he continues his work with genetics of pain disorders. The primary focus of his research career has been the search for genetic variation that contributes to greater pain sensitivity and increased risk for chronic pain disease. He has worked for over a decade with genomic techniques, including both quantitative trait locus (QTL) mapping in the mouse and genetic association in human pain cohorts, investigating a number of pain-related diseases and phenotypes. Dr. Smith has published over 40 journal articles and book chapters, and presented his work at several international meetings. His work with projects such as the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study has resulted in a number of novel genes being recognized as genetic risk factors for pain.


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