<p class="first" id="d11091835e391">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.
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