title: GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person.
abstract: Circadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 × 10(-18); rs9479402 near VIP, P=3.9 × 10(-11); rs55694368 near PER2, P=2.6 × 10(-9); rs35833281 near HCRTR2, P=3.7 × 10(-9); rs11545787 near RASD1, P=1.4 × 10(-8); rs11121022 near PER3, P=2.0 × 10(-8); rs9565309 near FBXL3, P=3.5 × 10(-8). Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies.
authors.affiliation: 23andMe, Inc., 899 W Evelyn Avenue, Mountain View, California 94043 USA.
authors.forename: Youna
authors.initials: Y
authors.lastname: Hu
authors.affiliation: 23andMe, Inc., 899 W Evelyn Avenue, Mountain View, California 94043 USA.
authors.forename: Alena
authors.initials: A
authors.lastname: Shmygelska
authors.affiliation: 23andMe, Inc., 899 W Evelyn Avenue, Mountain View, California 94043 USA.|Department of Biological Sciences, San Jose State University, San Jose, California 95112 USA.
authors.forename: David
authors.initials: D
authors.lastname: Tran
authors.affiliation: 23andMe, Inc., 899 W Evelyn Avenue, Mountain View, California 94043 USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Eriksson
authors.affiliation: 23andMe, Inc., 899 W Evelyn Avenue, Mountain View, California 94043 USA.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Tung
authors.affiliation: 23andMe, Inc., 899 W Evelyn Avenue, Mountain View, California 94043 USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hinds
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002940:Circadian Rhythm / Q000235:genetics*; D003863:Depression / Q000453:epidemiology*; D044783:F-Box Proteins / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D064446:Orexin Receptors / Q000235:genetics; D056950:Period Circadian Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics; D012891:Sleep Apnea Syndromes / Q000453:epidemiology*; D007319:Sleep Initiation and Maintenance Disorders / Q000453:epidemiology*; D014660:Vasoactive Intestinal Peptide / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D044783:F-Box Proteins; C519795:FBXL3 protein, human; C578626:HCRTR2 protein, human; D064446:Orexin Receptors; C421902:PER2 protein, human; C512644:PER3 protein, human; D056950:Period Circadian Proteins; C400132:RASD1 protein, human; D020710:RGS Proteins; C107413:RGS16 protein; D014660:Vasoactive Intestinal Peptide; D018631:ras Proteins
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