title: Common variants in DRD2 are associated with sleep duration: the CARe consortium.
abstract: Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for ∼50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes. African-Americans had additional genome-wide genotypes. Four cohorts provided replication. A SNP (rs17601612) in the dopamine D2 receptor gene (DRD2) was significantly associated with sleep duration (P = 9.8 × 10(-7)). Conditional analysis identified a second DRD2 signal with opposite effects on sleep duration. In exploratory analysis, suggestive association was observed for rs17601612 with polysomnographically determined sleep latency (P = 0.002). The lead DRD2 signal was recently identified in a schizophrenia GWAS, and a genetic risk score of 11 additional schizophrenia GWAS loci genotyped on the IBC array was also associated with longer sleep duration (P = 0.03). These findings support a role for DRD2 in influencing sleep duration. Our work motivates future pharmocogenetics research on alerting agents such as caffeine and modafinil that interact with the dopaminergic pathway and further investigation of genetic overlap between sleep and neuro-psychiatric traits.
authors.affiliation: Division of Sleep and Circadian Disorders and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA, bcade@partners.org.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Cade
authors.affiliation: Division of Sleep and Circadian Disorders and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA, VA Boston Healthcare System, Boston, MA 02132, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Gottlieb
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Diane S
authors.initials: DS
authors.lastname: Lauderdale
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Aron S
authors.initials: AS
authors.lastname: Buchman
authors.affiliation: School of Public Health, Jackson State University, Jackson, MS 39217, USA.
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Buxbaum
authors.affiliation: Department of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Evans
authors.affiliation: Department of Internal Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Tibor
authors.initials: T
authors.lastname: Fülöp
authors.affiliation: Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Division of Pulmonary and Critical Care Medicine and.
authors.forename: Sina A
authors.initials: SA
authors.lastname: Gharib
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: W Craig
authors.initials: WC
authors.lastname: Johnson
authors.affiliation: Institute of Human Genomic Study, Korea University Ansan Medical Center, Ansan 425-707, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Larkin
authors.affiliation: Institute of Human Genomic Study, Korea University Ansan Medical Center, Ansan 425-707, Republic of Korea.
authors.forename: Seung Ku
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Lim
authors.affiliation: Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Naresh M
authors.initials: NM
authors.lastname: Punjabi
authors.affiliation: Institute of Human Genomic Study, Korea University Ansan Medical Center, Ansan 425-707, Republic of Korea, Division of Pulmonary, Sleep and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 425-707, Republic of Korea.
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Stone
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tranah
authors.affiliation: Division of Sleep and Circadian Disorders and.
authors.forename: Jia
authors.initials: J
authors.lastname: Weng
authors.affiliation: Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA 94107, USA, San Francisco VA Medical Center, San Francisco, CA 94121, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
authors.affiliation: Department of Neurology and Sleep Medicine Center, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Zee
authors.affiliation: Division of Sleep and Circadian Disorders and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA, Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
authors.affiliation: Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Division of Sleep and Circadian Disorders and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA, Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.affiliation: Division of Sleep and Circadian Disorders and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA, Center for Human Genetic Research and Department of Anesthesia, Pain, and Critical Care Medicine, Massachusetts General Hospital, Boston, MA 02114, USA and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
mesh_terms: D015331:Cohort Studies; D005006:Ethnicity; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017286:Polysomnography; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012890:Sleep / Q000235:genetics*; D013997:Time Factors
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2