{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:10:07Z","timestamp":1793139007546,"version":"4.5.0"},"posted":{"date-parts":[[2025,10,13]]},"group-title":"Genetic and Genomic Medicine","reference-count":99,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,20]]},"abstract":"<jats:p>Alzheimer's disease (AD) is the most common cause of dementia, with global case numbers projected to reach 153 million in 2050. AD is highly heritable, with twin-based heritability estimates of 60-80%. While 1,200 causal loci are predicted to exist for AD, approximately 80 have been associated with AD in two recent studies, suggesting that many loci remain to be discovered. Here, we analyzed data from 109,479 cases, 74,141 proxy cases, 2,131,799 controls, and 499,708 proxy controls from diverse ancestries, identifying 118 loci in a multi-ancestry analysis and 9 additional loci in ancestry-specific analyses, 48 of which are new. We identified new AD risk genes, prioritized potential drug targets, and identified microglia and, for the first time, several neuronal cell types enriched for AD-associated genetic risk. Moreover, we improved polygenic prediction and estimated a single-nucleotide polymorphism (SNP) heritability of 16%. Together, our findings offer insights into the genetic architecture and potential pathobiology of AD, as well as specific targets for future drug development research.<\/jats:p>","DOI":"10.1101\/2025.10.10.25337470","type":"posted-content","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T11:55:25Z","timestamp":1760529325000},"source":"Crossref","is-referenced-by-count":8,"title":["Genomic analyses reveal new insights into Alzheimer's disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0682-7880","authenticated-orcid":false,"given":"Emil","family":"Uffelmann","sequence":"first","affiliation":[{"name":"Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-4806","authenticated-orcid":false,"given":"Douglas P","family":"Wightman","sequence":"additional","affiliation":[{"name":"Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8179-2788","authenticated-orcid":false,"given":"Shahram","family":"Bahrami","sequence":"additional","affiliation":[{"name":"Centre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey A","family":"Shadrin","sequence":"additional","affiliation":[{"name":"Centre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Fominykh","sequence":"additional","affiliation":[{"name":"Centre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Ojima","sequence":"additional","affiliation":[{"name":"Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Benner","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, California, United States of America;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1106-4610","authenticated-orcid":false,"given":"Elisa","family":"Moreno","sequence":"additional","affiliation":[{"name":"HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian I","family":"Campos","sequence":"additional","affiliation":[{"name":"Regeneron Genetics Center, Tarrytown, NY, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper Q","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Minois-Genin","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hei Man","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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