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

被引：35

作者：

Cade, Brian E. ^{[1
,3
]}

Gottlieb, Daniel J. ^{[1
,3
,4
]}

Lauderdale, Diane S. ^{[5
]}

Bennett, David A. ^{[6
]}

Buchman, Aron S. ^{[6
]}

Buxbaum, Sarah G. ^{[7
]}

De Jager, Philip L. ^{[2
]}

Evans, Daniel S. ^{[8
]}

Fueloep, Tibor ^{[9
]}

Gharib, Sina A. ^{[10
]}

Johnson, W. Craig ^{[11
]}

Kim, Hyun ^{[12
]}

Larkin, Emma K. ^{[13
]}

Lee, Seung Ku ^{[12
]}

Lim, Andrew S. ^{[14
]}

Punjabi, Naresh M. ^{[15
]}

Shin, Chol ^{[12
,16
]}

Stone, Katie L. ^{[8
]}

Tranah, Gregory J. ^{[8
]}

Weng, Jia ^{[1
]}

Yaffe, Kristine ^{[17
,18
,19
,20
]}

Zee, Phyllis C. ^{[21
,22
]}

Patel, Sanjay R. ^{[1
,3
,23
]}

Zhu, Xiaofeng ^{[24
]}

Redline, Susan ^{[1
,3
,23
]}

Saxena, Richa ^{[1
,3
,25
,26
,27
]}

机构：

[1] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Neurol & Psychiat, 75 Francis St, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA

[4] VA Boston Healthcare Syst, Boston, MA 02132 USA

[5] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA

[6] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

[7] Jackson State Univ, Sch Publ Hlth, Jackson, MS 39217 USA

[8] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA

[9] Univ Mississippi, Dept Internal Med, Med Ctr, Jackson, MS 39216 USA

[10] Univ Washington, Div Pulm & Crit Care Med, UW Med Sleep Ctr, Computat Med Core,Ctr Lung Biol, Seattle, WA 98195 USA

[11] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[12] Korea Univ, Ansan Med Ctr, Inst Human Genom Study, Ansan 465707, South Korea

[13] Vanderbilt Univ, Med Ctr, Div Allergy Pulm & Crit Care, Dept Med, Nashville, TN 37232 USA

[14] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med, Div Neurol, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada

[15] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[16] Korea Univ, Ansan Hosp, Dept Internal Med, Div Pulm Sleep & Crit Care Med, Ansan 425707, South Korea

[17] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94107 USA

[18] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94107 USA

[19] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA

[20] San Francisco VA Med Ctr, San Francisco, CA 94121 USA

[21] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA

[22] Northwestern Univ, Sleep Med Ctr, Chicago, IL 60611 USA

[23] Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA

[24] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA

[25] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[26] Massachusetts Gen Hosp, Dept Anesthesia Pain & Crit Care Med, Boston, MA 02114 USA

[27] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA

来源：

HUMAN MOLECULAR GENETICS | 2016年 / 25卷 / 01期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; D2 RECEPTOR GENE; HUMAN-BRAIN; DOPAMINE-RECEPTORS; OSTEOPOROTIC FRACTURES; ADENOSINE A(2A); HUMAN STRIATUM; METAANALYSIS; DESIGN; LOCI;

D O I：

10.1093/hmg/ddv434

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：167 / 179

页数：13

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