☆ 4.5 Article

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

HUMAN MOLECULAR GENETICS (2016)

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Journal

HUMAN MOLECULAR GENETICS
Volume 25, Issue 1, Pages 167-179

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddv434

Keywords

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Categories

Biochemistry & Molecular Biology Genetics & Heredity

Funding

  1. National Institutes of Health [T32-HL007901-16, R01-HL113338-02, N01-HC-65226, HHSN268200625226C, RO1 HL46380-01-16, M01-RR-00080, N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321, U01HL064360, R01AG017917, P30AG010161, R01AG015819, R01AG024480, R01NS078009, R01AG036836, R01AG030146]
  2. NIH [R21 HL121728]
  3. National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]
  4. National Human Genome Research Institute [U01HG004402]
  5. National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]
  6. National Institute of Neurological Disorders and Stroke
  7. National Institute on Aging [AG023629, P30AG10161, R01AG15819, R01AG24871, R01AG26147, R01AG26916, P01AG09466, P01AG14449, K08AG00849, K23AG23675, R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576]
  8. University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]
  9. Northwestern University [HHSN268201300027C]
  10. University of Minnesota [HHSN268201300028C, U01 HL053934]
  11. Kaiser Foundation Research Institute [HHSN268201300029C]
  12. Johns Hopkins University School of Medicine [HHSN268200900041C]
  13. Intramural Research Program of the National Institute on Aging
  14. National Institute on Minority Health and Health Disparities
  15. MESA [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, CTSA UL1-RR-024156]
  16. Case Western University [U01 HL063463]
  17. University of California, Davis [U01 HL053916]
  18. University of Arizona [U01 HL053938]
  19. University of Pittsburgh [U01 HL077813]
  20. Boston University [U01 HL053941]
  21. MedStar Research Institute [U01 HL063429]
  22. Johns Hopkins University [U01 HL053937]
  23. Korean Genome Analysis Project [4845-301]
  24. Korean Genome and Epidemiology Study [2001-347-6111-221, 2002-347-6111-221]
  25. Korea Biobank Project [4851-307, KBP-2013-25]
  26. Korea Center for Disease Control and Prevention, Republic of Korea
  27. Illinois Department of Public Health
  28. Elsie Heller Brain Bank Endowment Fund
  29. Robert C. Borwell Chair of Neurological Sciences
  30. National Institute of Arthritis and Musculoskeletal and Skin Diseases [RC2ARO58973]
  31. National Center for Research Resources
  32. NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583]
  33. [HHSN268201200036C]
  34. [HHSN268200800007C]
  35. [N01 HC55222]
  36. [N01HC85079]
  37. [N01HC85080]
  38. [N01HC85081]
  39. [N01HC85082]
  40. [N01HC85083]
  41. [N01HC85086]
  42. [U01 AG18197]
  43. [U01-AG027810]
  44. [UL1 RR024140]
  45. [R01HL087641]
  46. [R01HL59367]
  47. [R01HL086694]
  48. [HL080295]
  49. [AG0005]
  50. [HHSN268201300046C]
  51. [HHSN268201300047C]
  52. [HHSN268201300048C]
  53. [HHSN268201300049C]
  54. [HHSN268201300050C]
  55. [R01 HL071194]
  56. [R01 HL070848]
  57. [R01 HL070847]
  58. [R01 HL070842]
  59. [R01 HL070841]
  60. [R01 HL070837]
  61. [R01 HL070838]
  62. [R01 HL070839]
  63. DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS [N01HC085082, N01HC085080, N01HC095168, N01HC085083, N01HC095165, N01HC095166, N01HC095169, N01HC095160, N01HC085086, N01HC095164, N01HC085081, N01HC055222, N01HC095162, N01HC095167, N01HC025195, N01HC095161, N01HC095163, N01HC085079, N01HC095159] Funding Source: NIH RePORTER
  64. EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [U54HD083211] Funding Source: NIH RePORTER
  65. NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024140, UL1RR025005, M01RR000080, UL1RR024156] Funding Source: NIH RePORTER
  66. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007901, R01HL070848, U01HL053937, R01HL070838, R01HL071194, R01HL087641, R01HL070842, U01HL064360, U01HL080295, R01HL070847, R01HL070839, U01HL053941, U01HL063463, R01HL070841, R01HL086694, R01HL070837, R01HL046380, R01HL076784, R01HL092577, R01HL113338, U01HL077813, U01HL053938, R01HL059367, R21HL121728, R01HL080295] Funding Source: NIH RePORTER
  67. NATIONAL HUMAN GENOME RESEARCH INSTITUTE [U01HG004402] Funding Source: NIH RePORTER
  68. NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR035583, U01AR045614, R01AR035582, U01AR045583, R01AR035584, U01AR045654, U01AR045580, U01AR045632, U01AR045647] Funding Source: NIH RePORTER
  69. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS078009] Funding Source: NIH RePORTER
  70. NATIONAL INSTITUTE ON AGING [R01AG026720, R01AG026916, K23AG023675, R01AG028321, R01AG005394, R01AG017917, R01AG036836, K08AG000849, RF1AG015819, P01AG014449, U01AG027810, R01AG026147, R01AG027574, P30AG010161, R01AG015819, R56AG023629, R01AG023629, U01AG018197, R01AG030146, R01AG027576, R01AG024871, R01AG005407, R01AG024480, P01AG009466] Funding Source: NIH RePORTER
  71. National Institute on Minority Health and Health Disparities [P20MD006899] Funding Source: NIH RePORTER
  72. OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP1OD006849] Funding Source: NIH RePORTER

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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 similar to 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 x 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.

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