Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits

被引：207

作者：

Hammerschlag, Anke R. ^{[1
]}

Stringer, Sven ^{[1
]}

de Leeuw, Christiaan A. ^{[1
]}

Sniekers, Suzanne ^{[1
]}

Taskesen, Erdogan ^{[1
,2
]}

Watanabe, Kyoko ^{[1
]}

Blanken, Tessa F. ^{[3
,4
,5
]}

Dekker, Kim ^{[3
]}

te Lindert, Bart H. W. ^{[3
]}

Wassing, Rick ^{[3
]}

Jonsdottir, Ingileif ^{[6
,7
]}

Thorleifsson, Gudmar ^{[6
]}

Stefansson, Hreinn ^{[6
]}

Gislason, Thorarinn ^{[7
,8
]}

Berger, Klaus ^{[9
]}

Schormair, Barbara ^{[10
,11
]}

Wellmann, Juergen ^{[9
]}

Winkelmann, Juliane ^{[10
,11
,12
,13
]}

Stefansson, Kari ^{[6
,7
]}

Oexle, Konrad ^{[10
]}

Van Someren, Eus J. W. ^{[3
,4
,5
]}

Posthuma, Danielle ^{[1
,14
]}

机构：

[1] Vrije Univ Amsterdam, Amsterdam Neurosci, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, Amsterdam, Netherlands

[2] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam Neurosci, Amsterdam, Netherlands

[3] Netherlands Inst Neurosci, Dept Sleep & Cognit, Amsterdam, Netherlands

[4] Vrije Univ Amsterdam, Amsterdam Neurosci, Dept Integrat Neurophysiol, Amsterdam, Netherlands

[5] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands

[6] Amgen Inc, deCODE Genet, Reykjavik, Iceland

[7] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland

[8] Natl Univ Hosp Iceland, Dept Resp Med & Sleep, Landspitali, Reykjavik, Iceland

[9] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany

[10] Helmholtz Zentrum Munchen, Inst Neurogen, Munich, Germany

[11] Tech Univ Munich, Inst Human Genet, Munich, Germany

[12] Tech Univ Munich, Klinikum Rechts Isar, Neurol Klin & Poliklin, Munich, Germany

[13] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[14] Vrije Univ Amsterdam, Med Ctr, Amsterdam Neurosci, Dept Clin Genet, Amsterdam, Netherlands

来源：

NATURE GENETICS | 2017年 / 49卷 / 11期

基金：

欧洲研究理事会;

关键词：

RESTLESS LEGS SYNDROME; MYOCARDIAL-INFARCTION; PERSISTENT INSOMNIA; SLEEP DISTURBANCE; SEX-DIFFERENCES; HUMAN HEIGHT; POPULATION; EPIDEMIOLOGY; METAANALYSIS; VARIANTS;

D O I：

10.1038/ng.3888

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Persistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 x 10(-8)) has previously been implicated in restless legs syndrome (RLS). Additional analyses favor the hypothesis that MEIS1 exhibits pleiotropy for insomnia and RLS and show that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup within the cases. Sex-specific analyses suggest that there are different genetic architectures between the sexes in addition to shared genetic factors. We show substantial positive genetic correlation of insomnia complaints with internalizing personality traits and metabolic traits and negative correlation with subjective well-being and educational attainment. These findings provide new insight into the genetic architecture of insomnia.

引用

页码：1584 / +

页数：12

共 66 条

[1] UK Biobank Data: Come and Get It [J].

Allen, Naomi E. ;

Sudlow, Cathie ;

Peakman, Tim ;

Collins, Rory .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[2] Thalamic glutamate/glutamine in restless legs syndrome Increased and related to disturbed sleep [J].

Allen, Richard P. ;

Barker, Peter B. ;

Horska, Alena ;

Earley, Christopher J. .

NEUROLOGY, 2013, 80 (22) :2028-2034

[3] Genetic variants in RBFOX3 are associated with sleep latency [J].

Amin, Najaf ;

Allebrandt, Karla V. ;

van der Spek, Ashley ;

Mueller-Myhsok, Bertram ;

Hek, Karin ;

Teder-Laving, Maris ;

Hayward, Caroline ;

Esko, Tonu ;

van Mill, Josine G. ;

Mbarek, Hamdi ;

Watson, Nathaniel F. ;

Melville, Scott A. ;

Del Greco, Fabiola M. ;

Byrne, Enda M. ;

Oole, Edwin ;

Kolcic, Ivana ;

Chen, Ting-hsu ;

Evans, Daniel S. ;

Coresh, Josef ;

Vogelzangs, Nicole ;

Karjalainen, Juha ;

Willemsen, Gonneke ;

Gharib, Sina A. ;

Zgaga, Lina ;

Mihailov, Evelin ;

Stone, Katie L. ;

Campbell, Harry ;

Brouwer, Rutger Ww ;

Demirkan, Ayse ;

Isaacs, Aaron ;

Dogas, Zoran ;

Marciante, Kristin D. ;

Campbell, Susan ;

Borovecki, Fran ;

Luik, Annemarie I. ;

Li, Man ;

Hottenga, Jouke Jan ;

Huffman, Jennifer E. ;

van den Hout, Mirjam C. G. N. ;

Cummings, Steven R. ;

Aulchenko, Yuru S. ;

Gehrman, Philip R. ;

Uitterlinden, Andre G. ;

Wichmann, Heinz-Erich ;

Muller-Nurasyid, Martina ;

Fehrmann, Rudolf S. N. ;

Montgomery, Grant W. ;

Hofman, Albert ;

Kao, Wen Hong Linda ;

Oostra, Ben A. .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2016, 24 (10) :1488-1495

[4]

[Anonymous], SLEEP MED REV

[5] The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].

Ardlie, Kristin G. ;

DeLuca, David S. ;

Segre, Ayellet V. ;

Sullivan, Timothy J. ;

Young, Taylor R. ;

Gelfand, Ellen T. ;

Trowbridge, Casandra A. ;

Maller, Julian B. ;

Tukiainen, Taru ;

Lek, Monkol ;

Ward, Lucas D. ;

Kheradpour, Pouya ;

Iriarte, Benjamin ;

Meng, Yan ;

Palmer, Cameron D. ;

Esko, Tonu ;

Winckler, Wendy ;

Hirschhorn, Joel N. ;

Kellis, Manolis ;

MacArthur, Daniel G. ;

Getz, Gad ;

Shabalin, Andrey A. ;

Li, Gen ;

Zhou, Yi-Hui ;

Nobel, Andrew B. ;

Rusyn, Ivan ;

Wright, Fred A. ;

Lappalainen, Tuuli ;

Ferreira, Pedro G. ;

Ongen, Halit ;

Rivas, Manuel A. ;

Battle, Alexis ;

Mostafavi, Sara ;

Monlong, Jean ;

Sammeth, Michael ;

Mele, Marta ;

Reverter, Ferran ;

Goldmann, Jakob M. ;

Koller, Daphne ;

Guigo, Roderic ;

McCarthy, Mark I. ;

Dermitzakis, Emmanouil T. ;

Gamazon, Eric R. ;

Im, Hae Kyung ;

Konkashbaev, Anuar ;

Nicolae, Dan L. ;

Cox, Nancy J. ;

Flutre, Timothee ;

Wen, Xiaoquan ;

Stephens, Matthew .

SCIENCE, 2015, 348 (6235) :648-660

[6] Insomnia as a predictor of depression: A meta-analytic evaluation of longitudinal epidemiological studies [J].

Baglioni, Chiara ;

Battagliese, Gemma ;

Feige, Bernd ;

Spiegelhalder, Kai ;

Nissen, Christoph ;

Voderholzer, Ulrich ;

Lombardo, Caterina ;

Riemann, Dieter .

JOURNAL OF AFFECTIVE DISORDERS, 2011, 135 (1-3) :10-19

[7] Familial incidence of insomnia [J].

Bastien, CH ;

Morin, C .

JOURNAL OF SLEEP RESEARCH, 2000, 9 (01) :49-54

[8] Family history of insomnia in a population-based sample [J].

Beaulieu-Bonneau, Simon ;

LeBlanc, Melanie ;

Merette, Chantal ;

Dauvilliers, Yves ;

Morin, Charles M. .

SLEEP, 2007, 30 (12) :1739-1745

[9]

Bettolo A., 1931, STUDIUM, V21, P54

[10] 24-HOUR METABOLIC-RATE IN INSOMNIACS AND MATCHED NORMAL SLEEPERS [J].

BONNET, MH ;

ARAND, DL .

SLEEP, 1995, 18 (07) :581-588

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