Six Loci Support Shared Causal Variants

Colocalization analysis, which tests whether 2 traits share the same underlying variant, supported shared causal variants at 6 loci near APOE, HLA-B, NLGN1, AK5/DNAJB4, FAM114A2/GRIA1, and SATB1. The APOE signal showed near-complete colocalization (posterior probability, 0.9997). The APOE ε4 allele, which raises Alzheimer disease risk, was associated with lower insomnia risk and lower CRP. The investigators suggested this may reflect context-dependent roles in neuroimmune regulation, lipid metabolism, and glial biology.

Genes at the shared loci were enriched for immune and stress-response pathways, including interferon gamma response, tumor necrosis factor α signaling through NF-κB, and…