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

Anke R. Hammerschlag, Sven Stringer, Christiaan A. De Leeuw, Suzanne Sniekers, Erdogan Taskesen, Kyoko Watanabe, Tessa F. Blanken, Kim Dekker, Bart H.W. Te Lindert, Rick Wassing, Ingileif Jonsdottir, Gudmar Thorleifsson, Hreinn Stefansson, Thorarinn Gislason, Klaus Berger, Barbara Schormair, Juergen Wellmann, Juliane Winkelmann, Kari Stefansson, Konrad Oexle & 2 others Eus J.W. Van Someren, Danielle Posthuma

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 × 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.

Original languageEnglish
Pages (from-to)1584-1592
Number of pages9
JournalNature Genetics
Volume49
Issue number11
DOIs
Publication statusPublished - 1 Nov 2017

Cite this

Hammerschlag, Anke R. ; Stringer, Sven ; De Leeuw, Christiaan A. ; Sniekers, Suzanne ; Taskesen, Erdogan ; Watanabe, Kyoko ; Blanken, Tessa F. ; Dekker, Kim ; Te Lindert, Bart H.W. ; Wassing, Rick ; Jonsdottir, Ingileif ; Thorleifsson, Gudmar ; Stefansson, Hreinn ; Gislason, Thorarinn ; Berger, Klaus ; Schormair, Barbara ; Wellmann, Juergen ; Winkelmann, Juliane ; Stefansson, Kari ; Oexle, Konrad ; Van Someren, Eus J.W. ; Posthuma, Danielle. / Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. In: Nature Genetics. 2017 ; Vol. 49, No. 11. pp. 1584-1592.
@article{b7d3a51a6cba447f991a757cb619097d,
title = "Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits",
abstract = "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 × 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.",
author = "Hammerschlag, {Anke R.} and Sven Stringer and {De Leeuw}, {Christiaan A.} and Suzanne Sniekers and Erdogan Taskesen and Kyoko Watanabe and Blanken, {Tessa F.} and Kim Dekker and {Te Lindert}, {Bart H.W.} and Rick Wassing and Ingileif Jonsdottir and Gudmar Thorleifsson and Hreinn Stefansson and Thorarinn Gislason and Klaus Berger and Barbara Schormair and Juergen Wellmann and Juliane Winkelmann and Kari Stefansson and Konrad Oexle and {Van Someren}, {Eus J.W.} and Danielle Posthuma",
year = "2017",
month = "11",
day = "1",
doi = "10.1038/ng.3888",
language = "English",
volume = "49",
pages = "1584--1592",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "11",

}

Hammerschlag, AR, Stringer, S, De Leeuw, CA, Sniekers, S, Taskesen, E, Watanabe, K, Blanken, TF, Dekker, K, Te Lindert, BHW, Wassing, R, Jonsdottir, I, Thorleifsson, G, Stefansson, H, Gislason, T, Berger, K, Schormair, B, Wellmann, J, Winkelmann, J, Stefansson, K, Oexle, K, Van Someren, EJW & Posthuma, D 2017, 'Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits' Nature Genetics, vol. 49, no. 11, pp. 1584-1592. https://doi.org/10.1038/ng.3888

Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. / Hammerschlag, Anke R.; Stringer, Sven; De Leeuw, Christiaan A.; Sniekers, Suzanne; Taskesen, Erdogan; Watanabe, Kyoko; Blanken, Tessa F.; Dekker, Kim; Te Lindert, Bart H.W.; Wassing, Rick; Jonsdottir, Ingileif; Thorleifsson, Gudmar; Stefansson, Hreinn; Gislason, Thorarinn; Berger, Klaus; Schormair, Barbara; Wellmann, Juergen; Winkelmann, Juliane; Stefansson, Kari; Oexle, Konrad; Van Someren, Eus J.W.; Posthuma, Danielle.

In: Nature Genetics, Vol. 49, No. 11, 01.11.2017, p. 1584-1592.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits

AU - Hammerschlag, Anke R.

AU - Stringer, Sven

AU - De Leeuw, Christiaan A.

AU - Sniekers, Suzanne

AU - Taskesen, Erdogan

AU - Watanabe, Kyoko

AU - Blanken, Tessa F.

AU - Dekker, Kim

AU - Te Lindert, Bart H.W.

AU - Wassing, Rick

AU - Jonsdottir, Ingileif

AU - Thorleifsson, Gudmar

AU - Stefansson, Hreinn

AU - Gislason, Thorarinn

AU - Berger, Klaus

AU - Schormair, Barbara

AU - Wellmann, Juergen

AU - Winkelmann, Juliane

AU - Stefansson, Kari

AU - Oexle, Konrad

AU - Van Someren, Eus J.W.

AU - Posthuma, Danielle

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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 × 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.

AB - 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 × 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.

UR - http://www.scopus.com/inward/record.url?scp=85032434566&partnerID=8YFLogxK

U2 - 10.1038/ng.3888

DO - 10.1038/ng.3888

M3 - Article

VL - 49

SP - 1584

EP - 1592

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 11

ER -