Genome-wide association study

Neuroscience

Biology

Gene

Genotype

Single-nucleotide polymorphism

Heritability

Mendelian randomization

Candidate gene

Insomnia

Genetic variants

Genetics

Quantitative trait locus

Genetic architecture

Pharmacology

Nature Genetics

Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited. Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and gain insight into the pathways, tissue and cell types involved in insomnia complaints. We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping. The meta-analysis explained 2.6% of the variance. We show gene set enrichments for the axonal part of neurons, cortical and subcortical tissues, and specific cell types, including striatal, hypothalamic, and claustrum neurons. We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits. Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume. Our findings highlight key brain areas and cell types implicated in insomnia, and provide new treatment targets. Genome-wide analyses in &gt;1 million individuals identify new loci and pathways associated with insomnia. The findings implicate key brain areas and cell types in the neurobiology of insomnia and highlight potential targets for developing new treatments.

Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways