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

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-association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes of which one locus and five genes are 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 shows pleiotropy for insomnia and RLS, and that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup. Sex-specific analyses suggested different genetic architectures across sexes in addition to common genetic factors. We show substantial positive genetic overlap with internalizing and metabolic traits and negative overlap with subjective well-being and educational attainment. These findings provide novel insight into the genetic architecture of insomnia.