Summary: Researchers have identified seven genetic risk factors linked to insomnia.
Source: VU
An international research team has identified seven genes associated with insomnia for the first time. This discovery marks a significant step toward understanding the biological mechanisms that predispose people to chronic sleep problems and challenges the notion that insomnia is solely a psychological condition. The findings are published in Nature Genetics.
Background and significance
Insomnia is among the most common complaints in primary care and remains a persistent vulnerability for many individuals even after treatment. By pinpointing genetic risk factors, researchers led by Professors Danielle Posthuma (VU and VUmc) and Eus van Someren (Netherlands Institute for Neuroscience, VU and VUmc) have advanced efforts to explain why some people are biologically more likely to develop insomnia. Identifying these genes is an important step toward revealing the cellular and molecular pathways that influence sleep regulation and daytime functioning.
Hope and recognition for people with insomnia
Professor van Someren, a specialist in sleep medicine, says the new genetic findings open a route to understanding insomnia at the level of neuronal communication, which could eventually lead to new, targeted treatments. The results may also improve clinical recognition of insomnia. “Insomnia is too often dismissed as ‘all in your head.’ Our study shows that genetic factors contribute to the disorder,” he explains.
In a genome-wide analysis of 113,006 individuals, the research team found seven genes associated with insomnia complaints. These genes are involved in transcription regulation—the process by which DNA is read and transcribed into RNA—and exocytosis, the mechanism by which cells release signaling molecules to interact with their environment. One of the identified genes, MEIS1, had been previously implicated in other sleep-related disorders, including Periodic Limb Movements of Sleep (PLMS) and Restless Legs Syndrome (RLS). Collaboration with colleagues at the Institute of Neurogenomics in Munich supported the conclusion that variants in MEIS1 contribute to all three conditions, suggesting shared biological pathways despite their different clinical manifestations.
Genetic overlap with psychiatric and metabolic traits
The study revealed substantial genetic overlap between insomnia complaints and various psychiatric traits—especially anxiety, depression, and higher neuroticism—as well as lower subjective wellbeing. “These results help explain why insomnia frequently co-occurs with mood and anxiety disorders,” says neuroscientist Anke Hammerschlag (VU), the study’s first author. The genetic correlations indicate that shared biology partly underlies these co-occurring conditions.
Sex differences in genetic architecture and prevalence
Sex-specific analyses indicate that although many genetic factors are shared between men and women, some risk variants differ by sex. This suggests that, for part of the risk, distinct biological mechanisms may lead to insomnia in men and women. In the studied sample—primarily adults over fifty—insomnia prevalence also differed: 33% of women reported insomnia complaints compared with 24% of men.
How the genes were identified
Detecting these risk genes required large cohorts that combined genetic data with reliable sleep phenotypes. The UK Biobank, a large genetic cohort from the United Kingdom, did not include formal insomnia diagnoses but asked participants about difficulty falling or staying asleep. By integrating detailed sleep questionnaire data from the Dutch Sleep Registry (slaapregister.nl), researchers were able to classify participants according to an insomnia profile and link that phenotype to DNA. Combining information across cohorts increased the study’s power to discover associated genes and loci.
About this neuroscience research article
Funding: The study received support from the Netherlands Organization for Scientific Research and the European Research Council.
Source: Eus van Someren, VU
Original research: The findings are reported in the paper titled “Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits,” published in Nature Genetics (June 12, 2017).
Abstract (summary)
To identify genetic factors associated with persistent insomnia complaints, the authors conducted a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. The analysis identified three genomic loci and seven genes linked to insomnia complaints; one locus and five genes were further supported by joint analysis with an independent sample (n = 7,565). The strongest association involved MEIS1, previously linked to restless legs syndrome. Additional analyses support the view that MEIS1 exerts pleiotropic effects across insomnia and restless legs syndrome rather than the insomnia signal being explained solely by an RLS subgroup. Sex-specific results suggest partially different genetic architectures in men and women alongside shared risk factors. The study also documents positive genetic correlations between insomnia complaints and internalizing psychiatric traits and certain metabolic traits, and negative correlations with subjective wellbeing and educational attainment. These results offer new insight into the genetic architecture of insomnia and point to biological pathways that may underlie risk and comorbidity.