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Hum Mol Genet. 2016 Jan 1;25(1):167-79. doi: 10.1093/hmg/ddv434. Epub 2015 Oct 13.

Common variants in DRD2 are associated with sleep duration: the CARe consortium.

Author information

1
Division of Sleep and Circadian Disorders and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA, bcade@partners.org.
2
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.
3
Department of Health Studies, The University of Chicago, Chicago, IL 60637, USA.
4
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
5
School of Public Health, Jackson State University, Jackson, MS 39217, USA.
6
Department of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, MA 02115, USA.
7
California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
8
Department of Internal Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
9
Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Division of Pulmonary and Critical Care Medicine and.
10
Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
11
Institute of Human Genomic Study, Korea University Ansan Medical Center, Ansan 425-707, Republic of Korea.
12
Department of Medicine, Division of Allergy, Pulmonary and Critical Care, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
13
Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
14
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
15
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.
16
Division of Sleep and Circadian Disorders and.
17
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.
18
Department of Neurology and Sleep Medicine Center, Northwestern University, Chicago, IL 60611, USA.
19
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.
20
Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
21
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.

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.

PMID:
26464489
PMCID:
PMC4690488
DOI:
10.1093/hmg/ddv434
[Indexed for MEDLINE]
Free PMC Article

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