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

Nat Genet. 2017 Nov;49(11):1584-1592. doi: 10.1038/ng.3888. Epub 2017 Jun 12.

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.

MeSH terms

  • Adult
  • Alleles
  • Chromosome Mapping
  • Educational Status
  • Female
  • Gene Expression
  • Gene Frequency
  • Gene Regulatory Networks*
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Genome-Wide Association Study
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / genetics*
  • 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 / genetics*
  • Sleep Initiation and Maintenance Disorders / metabolism
  • Sleep Initiation and Maintenance Disorders / physiopathology
  • Sleep Initiation and Maintenance Disorders / psychology
  • Type D Personality

Substances

  • Homeodomain Proteins
  • MEIS1 protein, human
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins