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

Brian E. Cade, Daniel J. Gottlieb, Diane S. Lauderdale, David A. Bennett, Aron S. Buchman, Sarah G. Buxbaum, Philip L. De Jager, Daniel S. Evans, Tibor Fülöp, Sina A. Gharib, W. Craig Johnson, Hyun Kim, Emma K. Larkin, Seung Ku Lee, Andrew S. Lim, Naresh M Punjabi, Chol Shin, Katie L. Stone, Gregory J. Tranah, Jia WengKristine Yaffe, Phyllis C. Zee, Sanjay R. Patel, Xiaofeng Zhu, Susan Redline, Richa Saxena

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)167-179
Number of pages13
JournalHuman Molecular Genetics
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2016

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Sleep
Genes
Genome-Wide Association Study
African Americans
Single Nucleotide Polymorphism
Schizophrenia
Premature Mortality
Asian Americans
Dopamine D2 Receptors
Caffeine
Hispanic Americans
Psychiatry
Meta-Analysis
Chronic Disease
Genotype
Genome
Lung
Research

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Cade, B. E., Gottlieb, D. J., Lauderdale, D. S., Bennett, D. A., Buchman, A. S., Buxbaum, S. G., ... Saxena, R. (2016). Common variants in DRD2 are associated with sleep duration: The CARe consortium. Human Molecular Genetics, 25(1), 167-179. https://doi.org/10.1093/hmg/ddv434

Common variants in DRD2 are associated with sleep duration : The CARe consortium. / Cade, Brian E.; Gottlieb, Daniel J.; Lauderdale, Diane S.; Bennett, David A.; Buchman, Aron S.; Buxbaum, Sarah G.; De Jager, Philip L.; Evans, Daniel S.; Fülöp, Tibor; Gharib, Sina A.; Johnson, W. Craig; Kim, Hyun; Larkin, Emma K.; Lee, Seung Ku; Lim, Andrew S.; Punjabi, Naresh M; Shin, Chol; Stone, Katie L.; Tranah, Gregory J.; Weng, Jia; Yaffe, Kristine; Zee, Phyllis C.; Patel, Sanjay R.; Zhu, Xiaofeng; Redline, Susan; Saxena, Richa.

In: Human Molecular Genetics, Vol. 25, No. 1, 01.01.2016, p. 167-179.

Research output: Contribution to journalArticle

Cade, BE, Gottlieb, DJ, Lauderdale, DS, Bennett, DA, Buchman, AS, Buxbaum, SG, De Jager, PL, Evans, DS, Fülöp, T, Gharib, SA, Johnson, WC, Kim, H, Larkin, EK, Lee, SK, Lim, AS, Punjabi, NM, Shin, C, Stone, KL, Tranah, GJ, Weng, J, Yaffe, K, Zee, PC, Patel, SR, Zhu, X, Redline, S & Saxena, R 2016, 'Common variants in DRD2 are associated with sleep duration: The CARe consortium', Human Molecular Genetics, vol. 25, no. 1, pp. 167-179. https://doi.org/10.1093/hmg/ddv434
Cade BE, Gottlieb DJ, Lauderdale DS, Bennett DA, Buchman AS, Buxbaum SG et al. Common variants in DRD2 are associated with sleep duration: The CARe consortium. Human Molecular Genetics. 2016 Jan 1;25(1):167-179. https://doi.org/10.1093/hmg/ddv434
Cade, Brian E. ; Gottlieb, Daniel J. ; Lauderdale, Diane S. ; Bennett, David A. ; Buchman, Aron S. ; Buxbaum, Sarah G. ; De Jager, Philip L. ; Evans, Daniel S. ; Fülöp, Tibor ; Gharib, Sina A. ; Johnson, W. Craig ; Kim, Hyun ; Larkin, Emma K. ; Lee, Seung Ku ; Lim, Andrew S. ; Punjabi, Naresh M ; Shin, Chol ; Stone, Katie L. ; Tranah, Gregory J. ; Weng, Jia ; Yaffe, Kristine ; Zee, Phyllis C. ; Patel, Sanjay R. ; Zhu, Xiaofeng ; Redline, Susan ; Saxena, Richa. / Common variants in DRD2 are associated with sleep duration : The CARe consortium. In: Human Molecular Genetics. 2016 ; Vol. 25, No. 1. pp. 167-179.
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AU - Punjabi, Naresh M

AU - Shin, Chol

AU - Stone, Katie L.

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AU - Weng, Jia

AU - Yaffe, Kristine

AU - Zee, Phyllis C.

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