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Due to its increased power and interpretability, genetically regulated expression (GReX) analysis is an emerging approach to investigate the genetic mechanisms of complex diseases. Here, we conducted GReX analysis within and across 51 tissues on 39 LOAD GWAS data sets comprising 58,713 cases and controls from the Alzheimer\u2019s Disease Genetics Consortium (ADGC) and the International Genomics of Alzheimer\u2019s Project (IGAP). Meta-analysis across studies identified 216 unique significant genes, including 72 with no previously reported LOAD GWAS associations. Cross-brain-tissue and cross-GTEx models revealed eight additional genes significantly associated with LOAD. Conditional analysis of previously reported loci using established LOAD-risk variants identified eight genes reaching genome-wide significance independent of known signals. Moreover, the proportion of SNP-based heritability is highly enriched in genes identified by GReX analysis. In summary, GReX-based meta-analysis in LOAD identifies 216 genes (including 72 novel genes), illuminating the role of gene regulatory models in LOAD.<\/jats:p>","DOI":"10.1038\/s41398-021-01677-0","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T10:02:57Z","timestamp":1638784977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Genetically regulated expression in late-onset Alzheimer\u2019s disease implicates risk genes within known and novel loci"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1921-2797","authenticated-orcid":false,"given":"Hung-Hsin","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1619-6303","authenticated-orcid":false,"given":"Lauren E.","family":"Petty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Sha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Kuzma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Valladares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer\u2019s Disease Genetics Consortium, International Genomics of Alzheimer\u2019s Project","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-6519","authenticated-orcid":false,"given":"William","family":"Bush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9621-2942","authenticated-orcid":false,"given":"Adam C.","family":"Naj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric R.","family":"Gamazon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1346-1872","authenticated-orcid":false,"given":"Jennifer E.","family":"Below","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"1677_CR1","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","volume":"80","author":"LE Hebert","year":"2013","unstructured":"Hebert LE, Weuve J, Scherr PA, Evans DA. 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