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medRxiv : the preprint server for health sciences · 2025

Genomic analyses reveal new insights into Alzheimer's disease.

СтатьяПрепринтНазвание и аннотация: Перевод пока не подготовлен
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Uffelmann Emil, Wightman Douglas P, Bahrami Shahram, Shadrin Alexey A, Fominykh Vera, Ojima Takafumi, Jiang Chenyang, Benner Christian, Moreno Elisa, Campos Adrian I, Thomassen Jesper Q, Minois-Genin Emmanuel, Wu Hei Man, Walters G Bragi, Sherva Richard, Lin Tian, Bryois Julien, Krebs Kristi, Schipper Marijn, Narita Akira, Serretti Alessandro, Simonsen Anja H, van Seumeren Anna L, Corbett Anne, Knapskog Anne-Brita, Hartmann Annette M, den Braber Anouk, van Harten Argonde C, Harder Arvid, Rongve Arvid, Madsen Bengt O, Tijms Betty M, Aagaard Bitten, Lichtwarck Bjørn, Kirsebom Bjørn E, Creese Byron, Reynolds Chandra A, Hägg Sara, Karlsson Ida, Erikstrup Christian, Mikkelsen Christina, Ballard Clive, Aarsland Dag, Shigemizu Daichi, Rujescu Dan, Gudbjartsson Daniel, Aakhus Eivind, Sørensen Erik, Stordal Eystein, Duits Flora H, Wolters Frank J, Blanc Frederic, Biessels Geert Jan, Selbæk Geir, Bråthen Geir, Tamiya Gen, Waldemar Gunhild, Seelaar Harro, Eyjolfsdottir Helga, Holstege Henne, Bundgaard Henning, Zetterberg Henrik, Ullum Henrik, Skoog Ingmar, Medbøen Ingrid T, Saltvedt Ingvild, Feiring Ingvild H, Rektorova Irena, Gaziano J Michael, Haavik Jan, Hjerling-Leffler Jens, Luo Jiao, Snaedal Jon, Vijverberg Everard G B, Sealock Julia M, Blennow Kaj, Nordengen Kaja, Persson Karin, Scheffler Katja, Matsuda Koichi, Ozaki Kouichi, Pihlstrøm Lasse, Athanasiu Lavinia, Pålhaugen Lene, Hulsman Marc, Waern Margda, Averina Maria, Wettergreen Marianne, Moksnes Marta R, Huisman Martijn, Yamamoto Masayuki, Toft Mathias, Panizzon Matthew S, Bruun Mie Topholm, Ghanbari Mohsen, Franc Monique, Pedersen Nancy L, Bell Nathaniel Y, Tesi Niccoló, Pedersen Ole B, Frei Oleksandr, Bousiges Olivier, Svenningsson Per, Visser Pieter J, Li Qingqin S, Hauger Richard, Zhang Rui, Namba Shinichi, Sando Sigrid B, Kern Silke, Djurovic Srdjan, Thordardottir Steinunn, Phung Tanya N, Truelsen Thomas, Werge Thomas, Hansen Thomas F, Kyosaka Tomoki, Engstad Torgeir, Fladby Tormod, Merritt Victoria, Bergh Sverre, van der Flier Wiesje M, Wang Rujin, Stahl Eli A, Hooli Basavaraj, 23andMe Research Institute, LifeLines Cohort Study, DBDS Genomic consortium, Regeneron Genetics Center, Penn Medicine Biobank, GHS-RGC DiscovEHR collaboration, Mayo Clinic-RGC Project Generation, Colorado Center for Personalized Medicine – RGC Collaboration, UCLA-RGC ATLAS collaboration, INDIANA-CHALASANI, Mount Sinai Million Health Discoveries Program, Estonian Biobank research team, VA Million Veteran Program, Davis Lea K, Logue Mark W, Lehto Kelli, Zettergren Anna, Brumpton Ben M, Zeng Jian, Visscher Peter M, O'Reilly Paul F, Mahajan Anubha, Ferreira Manuel, Okada Yukinori, van der Lee Sven J, Ostrowski Sisse R, Frikke-Schmidt Ruth, Stefansson Hreinn, Heilbron Karl, Andreassen Ole A, Posthuma Danielle

Аннотация

Alzheimer's disease (AD) is the most common cause of dementia, with global case numbers projected to reach 153 million in 2050 1 . AD is highly heritable, with twin-based heritability estimates of 60-80% 2 . While 1,200 causal loci are predicted to exist for AD 3 , approximately 80 have been associated with AD in two recent studies 4,5 , suggesting that many loci remain to be discovered 6 . Here, we analyzed data from 183,620 AD cases and 2.6 million 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 19%. Together, our findings offer insights into the genetic architecture and potential pathobiology of AD, as well as specific targets for future drug development research.

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

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