Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits

被引：244

作者：

Lane, Jacqueline M. ^{[1
,2
,3
,4
]}

Liang, Jingjing ^{[5
]}

Vlasac, Irma ^{[1
,4
]}

Anderson, Simon G. ^{[6
,7
]}

Bechtold, David A. ^{[8
]}

Bowden, Jack ^{[9
,10
]}

Emsley, Richard ^{[11
]}

Gill, Shubhroz ^{[4
]}

Little, Max A. ^{[12
,13
]}

Luik, Annemarie I. ^{[14
]}

Loudon, Andrew

Scheer, Frank A. J. L. ^{[15
,16
]}

Purcell, Shaun M. ^{[4
,17
,18
]}

Kyle, Simon D.

Lawlor, Deborah A. ^{[9
,10
]}

Zhu, Xiaofeng ^{[5
]}

Redline, Susan ^{[19
,20
]}

Ray, David W. ^{[8
]}

Rutter, Martin K. ^{[8
]}

Saxena, Richa ^{[1
,2
,3
,4
,15
,16
]}

机构：

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

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

[3] Harvard Med Sch, Boston, MA 02115 USA

[4] Broad Inst, Cambridge, MA 02142 USA

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

[6] Univ Manchester, Sch Med Sci, Fac Biol Med & Hlth, Div Cardiovasc Sci, Manchester, Lancs, England

[7] Univ Oxford, Oxford Martin Sch, George Inst Global Hlth, Oxford, England

[8] Univ Manchester, Fac Biol Med & Hlth, Sch Med Sci, Div Endocrinol Diabet & Gastroenterol, Manchester, Lancs, England

[9] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England

[10] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

[11] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Hlth Sci,Div Populat Hlth Hlth Serv Res & Pri, Manchester, Lancs, England

[12] Aston Univ, Engn & Appl Sci, Birmingham, W Midlands, England

[13] MIT, Media Lab, Cambridge, MA USA

[14] Univ Oxford, Nuffield Dept Clin Neurosci, Sleep & Circadian Neurosci Inst, Oxford, England

[15] Harvard Med Sch, Div Sleep & Circadian Disorders, Brigham & Womens Hosp, Boston, MA USA

[16] Harvard Med Sch, Div Sleep Med, Boston, MA USA

[17] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA

[18] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA

[19] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA

[20] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA

来源：

NATURE GENETICS | 2017年 / 49卷 / 02期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

CHROMOSOME FUSION SITE; SLOW-WAVE SLEEP; SEROTONIN; 5-HT2A; COMMON VARIANTS; MEIS1; DURATION; RISK; SCHIZOPHRENIA; HERITABILITY; PROTEIN;

D O I：

10.1038/ng.3749

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality(1,2), affect 25-30% of adults worldwide(3). Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable(4-9) and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (r(g) = 0.29, P = 1.90 x 10(-13)) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): r(g) = 0.20, P = 3.12 x 10(-9); waist circumference: r(g) = 0.20, P = 2.12 x 10(-7)).

引用

页码：274 / 281

页数：8