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

Publication ,  Journal Article
Khoury, S; Wang, Q-P; Parisien, M; Gris, P; Bortsov, AV; Linnstaedt, SD; McLean, SA; Tungate, AS; Sofer, T; Lee, J; Louie, T; Redline, S ...
Published in: Sleep
March 12, 2021

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 = 2868) 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.

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Published In

Sleep

DOI

EISSN

1550-9109

Publication Date

March 12, 2021

Volume

44

Issue

3

Location

United States

Related Subject Headings

  • Sleep
  • Polymorphism, Single Nucleotide
  • Neurons
  • Neurology & Neurosurgery
  • Membrane Proteins
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Ethnicity
  • Drosophila melanogaster
 

Citation

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Khoury, S., Wang, Q.-P., Parisien, M., Gris, P., Bortsov, A. V., Linnstaedt, S. D., … Diatchenko, L. (2021). Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons. Sleep, 44(3). https://doi.org/10.1093/sleep/zsaa211
Khoury, Samar, Qiao-Ping Wang, Marc Parisien, Pavel Gris, Andrey V. Bortsov, Sarah D. Linnstaedt, Samuel A. McLean, et al. “Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons.Sleep 44, no. 3 (March 12, 2021). https://doi.org/10.1093/sleep/zsaa211.
Khoury S, Wang Q-P, Parisien M, Gris P, Bortsov AV, Linnstaedt SD, et al. Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons. Sleep. 2021 Mar 12;44(3).
Khoury, Samar, et al. “Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons.Sleep, vol. 44, no. 3, Mar. 2021. Pubmed, doi:10.1093/sleep/zsaa211.
Khoury S, Wang Q-P, Parisien M, Gris P, Bortsov AV, Linnstaedt SD, McLean SA, Tungate AS, Sofer T, Lee J, Louie T, Redline S, Kaunisto MA, Kalso EA, Munter HM, Nackley AG, Slade GD, Smith SB, Zaykin DV, Fillingim RB, Ohrbach R, Greenspan JD, Maixner W, Neely GG, Diatchenko L. Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons. Sleep. 2021 Mar 12;44(3).
Journal cover image

Published In

Sleep

DOI

EISSN

1550-9109

Publication Date

March 12, 2021

Volume

44

Issue

3

Location

United States

Related Subject Headings

  • Sleep
  • Polymorphism, Single Nucleotide
  • Neurons
  • Neurology & Neurosurgery
  • Membrane Proteins
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Ethnicity
  • Drosophila melanogaster