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

Hum Mol Genet
Authors
Keywords
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.

Year of Publication
2016
Journal
Hum Mol Genet
Volume
25
Issue
1
Pages
167-79
Date Published
2016 Jan 01
ISSN
1460-2083
URL
DOI
10.1093/hmg/ddv434
PubMed ID
26464489
PubMed Central ID
PMC4690488
Links
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R01AG024480 / AG / NIA NIH HHS / United States
N01HC55222 / HC / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
U01 AR45632 / AR / NIAMS NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
R01-HL-076784 / HL / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
R01AG24871 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
HHSN268201300049C / PHS HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
HHSN268201300048C / PHS HHS / United States
R01 HL070847 / HL / NHLBI NIH HHS / United States
AG0005 / AG / NIA NIH HHS / United States
HHSN268201300029C / PHS HHS / United States
P01AG14449 / AG / NIA NIH HHS / United States
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K08AG00849 / AG / NIA NIH HHS / United States
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