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

TY - JOUR

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

AU - Hammerschlag, A.R.

AU - Stringer, S.

AU - De Leeuw, C.A.

AU - Sniekers, S.

AU - Taskesen, E.

AU - Watanabe, K.

AU - Blanken, Tessa F

AU - Dekker, Kim

AU - Te Lindert, Bart H W

AU - Wassing, Rick

AU - Jonsdottir, I.

AU - Thorleifsson, G.

AU - Stefansson, H.

AU - Gislason, T.

AU - Berger, K.

AU - Schormair, B.

AU - Wellman, J.

AU - Winkelmann, J.

AU - Stefansson, K.

AU - Oexle, K.

AU - van Someren, E.J.W.

AU - Posthuma, Danielle

PY - 2017

Y1 - 2017

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.

U2 - 10.1038/ng1017-1558c

DO - 10.1038/ng1017-1558c

M3 - Article

SN - 1061-4036

VL - 49

SP - 1584

EP - 1592

JO - Nature Genetics

JF - Nature Genetics

ER -