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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.

TitleMulti-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons.
Publication TypePublication
Year2021
AuthorsKhoury 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 MAnneli, Kalso EA, Munter HMarkus, Nackley AG, Slade GD, Smith SB, Zaykin DV, Fillingim RB, Ohrbach R, Greenspan JD, Maixner W, G Neely G, Diatchenko L
JournalSleep
Volume44
Issue3
Date Published2021 03 12
ISSN1550-9109
KeywordsAnimals, Drosophila melanogaster, ethnic groups, Genetic Predisposition to Disease, genome-wide association study, Humans, Membrane Proteins, Neurons, Polymorphism, Single Nucleotide, sleep
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 = 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.

DOI10.1093/sleep/zsaa211
Alternate JournalSleep
PubMed ID33034629
PubMed Central IDPMC7953222
Grant ListHHSN268201000031C / HL / NHLBI NIH HHS / United States
HHSN268201800012C / HL / NHLBI NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
R01 HL113338 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
HHSN268201200008C / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
HHSN268201800013I / MD / NIMHD NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
K12 DE022793 / DE / NIDCR NIH HHS / United States
P01 NS045685 / NS / NINDS NIH HHS / United States
HHSN261201300005I / CA / NCI NIH HHS / United States
HHSN268201200008I / HL / NHLBI NIH HHS / United States
HHSN261201300004I / CA / NCI NIH HHS / United States
HHSN268201000021C / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
P30 AG028740 / AG / NIA NIH HHS / United States
R35 HL135818 / HL / NHLBI NIH HHS / United States
MS#: 
0525
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
ECI: 
Yes
Manuscript Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
Manuscript Status: 
Published