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Common variants in DRD2 are associated with sleep duration: the CARe consortium.
Wednesday,2016-08-17 16:27 America/Los_Angeles — zdrager
| Title | Common variants in DRD2 are associated with sleep duration: the CARe consortium. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Cade, BE, Gottlieb, DJ, Lauderdale, DS, Bennett, DA, Buchman, AS, Buxbaum, SG, De Jager, PL, Evans, DS, Fulop, T, Gharib, SA, W Johnson, C, Kim, H, Larkin, EK, Lee, SKu, Lim, AS, Punjabi, NM, Shin, C, Stone, KL, Tranah, GJ, Weng, J, Yaffe, K, Zee, PC, Patel, SR, Zhu, X, Redline, S, Saxena, R |
| Journal | Hum Mol Genet |
| Volume | 25 |
| Issue | 1 |
| Pagination | 167-79 |
| Date Published | 2016 Jan 1 |
| ISSN | 1460-2083 |
| Keywords | Cohort Studies, Ethnic Groups, Humans, Polymorphism, Single Nucleotide, Polysomnography, Receptors, Dopamine D2, Sleep, Time Factors |
| Abstract | <p>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.</p> |
| DOI | 10.1093/hmg/ddv434 |
| Alternate Journal | Hum. Mol. Genet. |
| PubMed ID | 26464489 |
| PubMed Central ID | PMC4690488 |
| Grant List | AG0005 / AG / NIA NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States DP1 OD006849 / OD / NIH HHS / United States HHSN268200625226C / / PHS HHS / United States HHSN268200800007C / / PHS HHS / United States HHSN268200900041C / / PHS HHS / United States HHSN268201100005C / / PHS HHS / United States HHSN268201100006C / / PHS HHS / United States HHSN268201100007C / / PHS HHS / United States HHSN268201100008C / / PHS HHS / United States HHSN268201100009C / / PHS HHS / United States HHSN268201100010C / / PHS HHS / United States HHSN268201100011C / / PHS HHS / United States HHSN268201100012C / / PHS HHS / United States HHSN268201200036C / / PHS HHS / United States HHSN268201300025C / / PHS HHS / United States HHSN268201300026C / / PHS HHS / United States HHSN268201300027C / / PHS HHS / United States HHSN268201300028C / / PHS HHS / United States HHSN268201300029C / / PHS HHS / United States HHSN268201300046C / / PHS HHS / United States HHSN268201300047C / / PHS 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