1. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.
- Author
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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, and Posthuma D
- Subjects
- Adult, Alleles, Chromosome Mapping, Educational Status, Female, Gene Expression, Gene Frequency, Genome-Wide Association Study, Humans, Male, Myeloid Ecotropic Viral Integration Site 1 Protein, Polymorphism, Single Nucleotide, Protein Interaction Mapping, Quality of Life psychology, Restless Legs Syndrome genetics, Restless Legs Syndrome metabolism, Restless Legs Syndrome physiopathology, Restless Legs Syndrome psychology, Sex Factors, Sleep Initiation and Maintenance Disorders metabolism, Sleep Initiation and Maintenance Disorders physiopathology, Sleep Initiation and Maintenance Disorders psychology, Type D Personality, Gene Regulatory Networks, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Homeodomain Proteins genetics, Neoplasm Proteins genetics, Sleep Initiation and Maintenance Disorders genetics
- 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.- Published
- 2017
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