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

• Published in: Sleep (New York, N.Y.) Vol. 44; no. 3; p. 1
• Main Authors: Khoury, Samar, Wang, Qiao-Ping, Parisien, Marc, Gris, Pavel, Bortsov, Andrey V, Linnstaedt, Sarah D, McLean, Samuel A, Tungate, Andrew S, Sofer, Tamar, Lee, Jiwon, Louie, Tin, Redline, Susan, Kaunisto, Mari Anneli, Kalso, Eija A, Munter, Hans Markus, Nackley, Andrea G, Slade, Gary D, Smith, Shad B, Zaykin, Dmitri V, Fillingim, Roger B, Ohrbach, Richard, Greenspan, Joel D, Maixner, William, Neely, G Gregory, Diatchenko, Luda
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.03.2021
• Subjects: Analysis; Animals; Basic Science of Sleep and Circadian Rhythms; Biotechnology industry; Drosophila melanogaster; Ethnicity; Genes; Genetic aspects; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Genomics; Humans; Membrane Proteins; Meta-analysis; Neurons; Neuropeptide Y; Physiological aspects; Polymorphism, Single Nucleotide - genetics; Sleep; Sleep - genetics; Sleep deprivation; Systematic review; North Carolina; Canada; United States; Quebec; sleep quality; genome-wide association study; sleep centers; MPP6
• ISSN: 0161-8105; 1550-9109; 1550-9109
• DOI: 10.1093/sleep/zsaa211

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.