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Here, we present the first genome-wide association study (GWAS) of subcortical LBA, estimated using a deep neural network applied to T1-weighted MRI scans from 41,957 cognitively normal participants in the UK Biobank. We computed LBA across 14 subcortical structures and identified 14 significant single-nucleotide polymorphisms (SNPs) across nine independent loci. These variants map to genes involved in cellular homeostasis, gene regulation, and synaptic and developmental signaling. A prominent signal emerged at the 17q21.31 haplotype, encompassing\n                    <jats:italic>MAPT<\/jats:italic>\n                    -related regulatory architecture, with significant associations across all subcortical regions. Across loci, we observed a recurring spatial pattern in which effect sizes are relatively larger in metabolically central structures such as the pallidum and thalamus compared to limbic regions. Together, these findings support a spatially structured pattern of genetic associations in subcortical brain aging. This work supports subcortical LBA as a genetically informed phenotype and provides a framework for linking common genetic variation to region-specific vulnerability and resilience in neurodegenerative disease.\n                  <\/jats:p>","DOI":"10.1007\/s11357-026-02453-y","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T10:27:16Z","timestamp":1785580036000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome-wide analysis of subcortical aging identifies a spatially structured pattern of genetic associations"],"prefix":"10.1007","author":[{"given":"Nicholas J.","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayati","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy S.","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen M.","family":"Vega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil N.","family":"Chaudhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyun C.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9254-9388","authenticated-orcid":false,"given":"Andrei","family":"Irimia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"2453_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.761954","volume":"13","author":"SG Popescu","year":"2021","unstructured":"Popescu SG, Glocker B, Sharp DJ, Cole JH. 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