Authors
Amber Zimmerman, Erika Almeraya Del Valle, Matthew Pahl, Fusun Doldur-Balli, Brendan Keenan, Patrick Liu, Zoe Shetty, Trisha Tsundupalli, Justin Palermo, Anitra Krishnan, James Pippin, Andrew Wells, Olivia Veatch, Alessandra Chesi, Philip Gehrman, Alex Keene, Allan Pack, Struan F A Grant
Published in
Genome research. Jul 30, 2026. Epub Jul 30, 2026.
Abstract
Genome-wide association studies (GWAS) have identified numerous loci for insomnia, yet functional validation of effector genes remains limited because most risk variants lie in noncoding regions, and the true causal gene is not known. Here, we use prior human cell-based variant-to-gene mapping to nominate six insomnia effector genes and test them in zebrafish, a tractable diurnal vertebrate model well-suited for sleep phenotyping. Our CRISPR-based behavioral screening identifies the MEIS1 ortholog, meis1b, as a regulator of sleep maintenance, with crispants displaying impaired nighttime-specific sleep maintenance and increased sleep latency. Comparative chromatin analyses reveal conserved regulatory architecture spanning the human insomnia-associated locus and selectively implicate meis1b, whereas the duplicated ohnolog meis1a was dispensable. Developmental profiling further shows that meis1b is expressed in cerebellar granule progenitors, paralleling human MEIS1 expression, and that its disruption impairs cerebellar development. Together, these findings establish zebrafish as an efficient vertebrate platform for functional interrogation of GWAS candidates and support an evolutionarily conserved cerebellar role for MEIS1 in sleep maintenance.
PMID:
42532834
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.
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