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Molecular psychiatry · 2024

X-chromosome-wide association study for Alzheimer's disease.

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Le Borgne Julie, Gomez Lissette, Heikkinen Sami, Amin Najaf, Ahmad Shahzad, Choi Seung Hoan, Bis Joshua, Grenier-Boley Benjamin, Rodriguez Omar Garcia, Kleineidam Luca, Young Juan, Tripathi Kumar Parijat, Wang Lily, Varma Achintya, Campos-Martin Rafael, van der Lee Sven, Damotte Vincent, de Rojas Itziar, Palmal Sagnik, EADB, GR@ACE, DEGESCO, EADI, GERAD, DemGene, FinnGen, ADGC, CHARGE, Lipton Richard, Reiman Eric, McKee Ann, De Jager Philip, Bush William, Small Scott, Levey Allan, Saykin Andrew, Foroud Tatiana, Albert Marilyn, Hyman Bradley, Petersen Ronald, Younkin Steven, Sano Mary, Wisniewski Thomas, Vassar Robert, Schneider Julie, Henderson Victor, Roberson Erik, DeCarli Charles, LaFerla Frank, Brewer James, Swerdlow Russell, Van Eldik Linda, Hamilton-Nelson Kara, Paulson Henry, Naj Adam, Lopez Oscar, Chui Helena, Crane Paul, Grabowski Thomas, Kukull Walter, Asthana Sanjay, Craft Suzanne, Strittmatter Stephen, Cruchaga Carlos, Leverenz James, Goate Alison, Kamboh M Ilyas, George-Hyslop Peter St, Valladares Otto, Kuzma Amanda, Cantwell Laura, Riemenschneider Matthias, Morris John, Slifer Susan, Dalmasso Carolina, Castillo Atahualpa, Küçükali Fahri, Peters Oliver, Schneider Anja, Dichgans Martin, Rujescu Dan, Scherbaum Norbert, Deckert Jürgen, Riedel-Heller Steffi, Hausner Lucrezia, Molina-Porcel Laura, Düzel Emrah, Grimmer Timo, Wiltfang Jens, Heilmann-Heimbach Stefanie, Moebus Susanne, Tegos Thomas, Scarmeas Nikolaos, Dols-Icardo Oriol, Moreno Fermin, Pérez-Tur Jordi, Bullido María J, Pastor Pau, Sánchez-Valle Raquel, Álvarez Victoria, Boada Mercè, García-González Pablo, Puerta Raquel, Mir Pablo, Real Luis M, Piñol-Ripoll Gerard, García-Alberca Jose María, Royo Jose Luís, Rodriguez-Rodriguez Eloy, Soininen Hilkka, de Mendonça Alexandre, Mehrabian Shima, Traykov Latchezar, Hort Jakub, Vyhnalek Martin, Thomassen Jesper Qvist, Pijnenburg Yolande A L, Holstege Henne, van Swieten John, Ramakers Inez, Verhey Frans, Scheltens Philip, Graff Caroline, Papenberg Goran, Giedraitis Vilmantas, Boland Anne, Deleuze Jean-François, Nicolas Gael, Dufouil Carole, Pasquier Florence, Hanon Olivier, Debette Stéphanie, Grünblatt Edna, Popp Julius, Ghidoni Roberta, Galimberti Daniela, Arosio Beatrice, Mecocci Patrizia, Solfrizzi Vincenzo, Parnetti Lucilla, Squassina Alessio, Tremolizzo Lucio, Borroni Barbara, Nacmias Benedetta, Spallazzi Marco, Seripa Davide, Rainero Innocenzo, Daniele Antonio, Bossù Paola, Masullo Carlo, Rossi Giacomina, Jessen Frank, Fernandez Victoria, Kehoe Patrick Gavin, Frikke-Schmidt Ruth, Tsolaki Magda, Sánchez-Juan Pascual, Sleegers Kristel, Ingelsson Martin, Haines Jonathan, Farrer Lindsay, Mayeux Richard, Wang Li-San, Sims Rebecca, DeStefano Anita, Schellenberg Gerard D, Seshadri Sudha, Amouyel Philippe, Williams Julie, van der Flier Wiesje, Ramirez Alfredo, Pericak-Vance Margaret, Andreassen Ole A, Van Duijn Cornelia, Hiltunen Mikko, Ruiz Agustín, Dupuis Josée, Martin Eden, Lambert Jean-Charles, Kunkle Brian, Bellenguez Céline

Аннотация

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты