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X-chromosome-wide association study for Alzheimer’s disease

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...

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Bibliographische Detailangaben
Hauptverfasser: Le Borgne, Julie (VerfasserIn) , Gomez, Lissette (VerfasserIn) , Heikkinen, Sami (VerfasserIn) , Amin, Najaf (VerfasserIn) , Ahmad, Shahzad (VerfasserIn) , Choi, Seung Hoan (VerfasserIn) , Bis, Joshua C. (VerfasserIn) , Grenier-Boley, Benjamin (VerfasserIn) , Rodriguez, Omar Garcia (VerfasserIn) , Kleineidam, Luca (VerfasserIn) , Young, Juan (VerfasserIn) , Tripathi, Kumar Parijat (VerfasserIn) , Wang, Lily (VerfasserIn) , Varma, Achintya (VerfasserIn) , Campos Martín, Rafael (VerfasserIn) , Lee, Sven J. van der (VerfasserIn) , Damotte, Vincent (VerfasserIn) , Rojas, Itziar de (VerfasserIn) , Palmal, Sagnik (VerfasserIn) , Lipton, Richard B. (VerfasserIn) , Reiman, Eric (VerfasserIn) , McKee, Ann C. (VerfasserIn) , Jager, Philip de (VerfasserIn) , Bush, William (VerfasserIn) , Small, Scott A. (VerfasserIn) , Levey, Allan (VerfasserIn) , Saykin, Andrew (VerfasserIn) , Foroud, Tatiana (VerfasserIn) , Albert, Marilyn (VerfasserIn) , Hyman, Bradley T. (VerfasserIn) , Petersen, Ronald (VerfasserIn) , Younkin, Steven (VerfasserIn) , Sano, Mary (VerfasserIn) , Wisniewski, Thomas (VerfasserIn) , Vassar, Robert (VerfasserIn) , Schneider, Julie (VerfasserIn) , Henderson, Victor (VerfasserIn) , Roberson, Erik (VerfasserIn) , DeCarli, Charles (VerfasserIn) , LaFerla, Frank (VerfasserIn) , Brewer, James (VerfasserIn) , Swerdlow, Russell (VerfasserIn) , Van Eldik, Linda J. (VerfasserIn) , Hamilton-Nelson, Kara (VerfasserIn) , Paulson, Henry L. (VerfasserIn) , Naj, Adam (VerfasserIn) , Lopez, Oscar (VerfasserIn) , Chui, Helena (VerfasserIn) , Crane, Paul (VerfasserIn) , Grabowski, Thomas (VerfasserIn) , Kukull, Walter (VerfasserIn) , Asthana, Sanjay (VerfasserIn) , Craft, Suzanne (VerfasserIn) , Strittmatter, Stephen (VerfasserIn) , Cruchaga, Carlos (VerfasserIn) , Leverenz, James (VerfasserIn) , Goate, Alison (VerfasserIn) , Kamboh, M. Ilyas (VerfasserIn) , St George-Hyslop, Peter (VerfasserIn) , Valladares, Otto (VerfasserIn) , Kuzma, Amanda (VerfasserIn) , Cantwell, Laura (VerfasserIn) , Riemenschneider, Matthias (VerfasserIn) , Morris, John (VerfasserIn) , Slifer, Susan (VerfasserIn) , Dalmasso, Carolina (VerfasserIn) , Castillo, Atahualpa (VerfasserIn) , Küçükali, Fahri (VerfasserIn) , Peters, Oliver Hubertus (VerfasserIn) , Schneider, Anja (VerfasserIn) , Dichgans, Martin (VerfasserIn) , Rujescu, Dan (VerfasserIn) , Scherbaum, Norbert (VerfasserIn) , Deckert, Jürgen (VerfasserIn) , Riedel-Heller, Steffi Gerlinde (VerfasserIn) , Hausner, Lucrezia (VerfasserIn) , Molina-Porcel, Laura (VerfasserIn) , Düzel, Emrah (VerfasserIn) , Grimmer, Timo (VerfasserIn) , Wiltfang, Jens (VerfasserIn) , Heilmann, Stefanie (VerfasserIn) , Moebus, Susanne (VerfasserIn) , Tegos, Thomas (VerfasserIn) , Scarmeas, Nikolaos (VerfasserIn) , Dols-Icardo, Oriol (VerfasserIn) , Moreno, Fermin (VerfasserIn) , Pérez-Tur, Jordi (VerfasserIn) , Bullido, María J. (VerfasserIn) , Pastor, Pau (VerfasserIn) , Sánchez-Valle, Raquel (VerfasserIn) , Álvarez, Victoria (VerfasserIn) , Boada, Mercè (VerfasserIn) , García-González, Pablo (VerfasserIn) , Puerta, Raquel (VerfasserIn) , Mir, Pablo (VerfasserIn) , Real, Luis M. (VerfasserIn) , Piñol-Ripoll, Gerard (VerfasserIn) , García-Alberca, Jose María (VerfasserIn) , Royo, Jose Luís (VerfasserIn) , Rodriguez-Rodriguez, Eloy (VerfasserIn) , Soininen, Hilkka (VerfasserIn) , Mendonça, Alexandre de (VerfasserIn) , Mehrabian, Shima (VerfasserIn) , Traykov, Latchezar (VerfasserIn) , Hort, Jakub (VerfasserIn) , Vyhnalek, Martin (VerfasserIn) , Thomassen, Jesper Qvist (VerfasserIn) , Pijnenburg, Yolande A. L. (VerfasserIn) , Holstege, Henne (VerfasserIn) , Swieten, John C. van (VerfasserIn) , Ramakers, Inez (VerfasserIn) , Verhey, Frans (VerfasserIn) , Scheltens, Philip (VerfasserIn) , Graff, Caroline (VerfasserIn) , Papenberg, Goran (VerfasserIn) , Giedraitis, Vilmantas (VerfasserIn) , Boland, Anne (VerfasserIn) , Deleuze, Jean-François (VerfasserIn) , Nicolas, Gaël (VerfasserIn) , Dufouil, Carole (VerfasserIn) , Pasquier, Florence (VerfasserIn) , Hanon, Olivier (VerfasserIn) , Debette, Stéphanie (VerfasserIn) , Grünblatt, Edna (VerfasserIn) , Popp, Julius (VerfasserIn) , Ghidoni, Roberta (VerfasserIn) , Galimberti, Daniela (VerfasserIn) , Arosio, Beatrice (VerfasserIn) , Mecocci, Patrizia (VerfasserIn) , Solfrizzi, Vincenzo (VerfasserIn) , Parnetti, Lucilla (VerfasserIn) , Squassina, Alessio (VerfasserIn) , Tremolizzo, Lucio (VerfasserIn) , Borroni, Barbara (VerfasserIn) , Nacmias, Benedetta (VerfasserIn) , Spallazzi, Marco (VerfasserIn) , Seripa, Davide (VerfasserIn) , Rainero, Innocenzo (VerfasserIn) , Daniele, Antonio (VerfasserIn) , Bossù, Paola (VerfasserIn) , Masullo, Carlo (VerfasserIn) , Rossi, Giacomina (VerfasserIn) , Jessen, Frank (VerfasserIn) , Fernandez, Victoria (VerfasserIn) , Kehoe, Patrick Gavin (VerfasserIn) , Frikke-Schmidt, Ruth (VerfasserIn) , Tsolaki, Magda (VerfasserIn) , Sánchez-Juan, Pascual (VerfasserIn) , Sleegers, Kristel (VerfasserIn) , Ingelsson, Martin (VerfasserIn) , Haines, Jonathan L. (VerfasserIn) , Farrer, Lindsay (VerfasserIn) , Mayeux, Richard (VerfasserIn) , Wang, Li-San (VerfasserIn) , Sims, Rebecca (VerfasserIn) , DeStefano, Anita (VerfasserIn) , Schellenberg, Gerard D. (VerfasserIn) , Seshadri, Sudha (VerfasserIn) , Amouyel, Philippe (VerfasserIn) , Williams, Julie (VerfasserIn) , Flier, Wiesje Maria van der (VerfasserIn) , Ramírez, Alfredo (VerfasserIn) , Pericak-Vance, Margaret Ann (VerfasserIn) , Andreassen, Ole A. (VerfasserIn) , Duijn, Cornelia van (VerfasserIn) , Hiltunen, Mikko (VerfasserIn) , Ruiz, Agustín (VerfasserIn) , Dupuis, Josée (VerfasserIn) , Martin, Eden (VerfasserIn) , Lambert, Jean-Charles (VerfasserIn) , Kunkle, Brian W. (VerfasserIn) , Bellenguez, Céline (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: June 2025
In: Molecular psychiatry
Year: 2025, Jahrgang: 30, Heft: 6, Pages: 2335-2346
ISSN:1476-5578
DOI:10.1038/s41380-024-02838-5
Online-Zugang:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1038/s41380-024-02838-5
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41380-024-02838-5
Resolving-System, kostenfrei: https://doi.org/10.25673/119306
Volltext
Verfasserangaben:Julie Le Borgne, Lissette Gomez, Sami Heikkinen, Najaf Amin, Shahzad Ahmad, Seung Hoan Choi, Joshua Bis, Benjamin Grenier-Boley, Omar Garcia Rodriguez, Luca Kleineidam, Juan Young, Kumar Parijat Tripathi, Lily Wang, Achintya Varma, Rafael Campos-Martin, Sven van der Lee, Vincent Damotte, Itziar de Rojas, Sagnik Palmal, Richard Lipton, Eric Reiman, Ann McKee, Philip De Jager, William Bush, Scott Small, Allan Levey, Andrew Saykin, Tatiana Foroud, Marilyn Albert, Bradley Hyman, Ronald Petersen, Steven Younkin, Mary Sano, Thomas Wisniewski, Robert Vassar, Julie Schneider, Victor Henderson, Erik Roberson, Charles DeCarli, Frank LaFerla, James Brewer, Russell Swerdlow, Linda Van Eldik, Kara Hamilton-Nelson, Henry Paulson, Adam Naj, Oscar Lopez, Helena Chui, Paul Crane, Thomas Grabowski, Walter Kukull, Sanjay Asthana, Suzanne Craft, Stephen Strittmatter, Carlos Cruchaga, James Leverenz, Alison Goate, M. Ilyas Kamboh, Peter St George-Hyslop, Otto Valladares, Amanda Kuzma, Laura Cantwell, Matthias Riemenschneider, John Morris, Susan Slifer, Carolina Dalmasso, Atahualpa Castillo, Fahri Küçükali, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Jürgen Deckert, Steffi Riedel-Heller, Lucrezia Hausner, Laura Molina-Porcel, Emrah Düzel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Oriol Dols-Icardo, Fermin Moreno, Jordi Pérez-Tur, María J. Bullido, Pau Pastor, Raquel Sánchez-Valle, Victoria Álvarez, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M. Real, Gerard Piñol-Ripoll, Jose María García-Alberca, Jose Luís Royo, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Alexandre de Mendonça, Shima Mehrabian, Latchezar Traykov, Jakub Hort, Martin Vyhnalek, Jesper Qvist Thomassen, Yolande A.L. Pijnenburg, Henne Holstege, John van Swieten, Inez Ramakers, Frans Verhey, Philip Scheltens, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Jean-François Deleuze, Gael Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Roberta Ghidoni, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Marco Spallazzi, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Paola Bossù, Carlo Masullo, Giacomina Rossi, Frank Jessen, Victoria Fernandez, Patrick Gavin Kehoe, Ruth Frikke-Schmidt, Magda Tsolaki, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Jonathan Haines, Lindsay Farrer, Richard Mayeux, Li-San Wang, Rebecca Sims, Anita DeStefano, Gerard D. Schellenberg, Sudha Seshadri, Philippe Amouyel, Julie Williams, Wiesje van der Flier, Alfredo Ramirez, Margaret Pericak-Vance, Ole A. Andreassen, Cornelia Van Duijn, Mikko Hiltunen, Agustín Ruiz, Josée Dupuis, Eden Martin, Jean-Charles Lambert, Brian Kunkle and Céline Bellenguez

MARC

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520 |a 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. 
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JSO |a "family":"Lambert","given":"Jean-Charles","role":"aut"},{"display":"Kunkle, Brian W.","family":"Kunkle","role":"aut","given":"Brian W."},{"given":"Céline","role":"aut","display":"Bellenguez, Céline","family":"Bellenguez"}]} 
SRT |a LEBORGNEJUXCHROMOSOM2025 

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