14 research outputs found
Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores (Nature Communications, (2021), 12, 1, (3417), 10.1038/s41467-021-22491-8)
No full textThe original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article. © The Author(s) 2023
Author correction: common variants in alzheimer’s disease and risk stratification by polygenic risk scores (nature communications, (2021), 12, 1, (3417), 10.1038/s41467-021-22491-8)
No full textde Rojas I., Moreno-Grau S., Tesi N., Grenier-Boley B., Andrade V., Jansen I.E., Pedersen N.L., Stringa N., Zettergren A., Hernández I., Montrreal L., Antúnez C., Antonell A., Tankard R.M., Bis J.C., Sims R., Bellenguez C., Quintela I., González-Perez A., Calero M., Franco-Macías E., Macías J., Blesa R., Cervera-Carles L., Menéndez-González M., Frank-García A., Royo J.L., Moreno F., Huerto Vilas R., Baquero M., Diez-Fairen M., Lage C., García-Madrona S., García-González P., Alarcón-Martín E., Valero S., Sotolongo-Grau O., Ullgren A., Naj A.C., Lemstra A.W., Benaque A., Pérez-Cordón A., Benussi A., Rábano A., Padovani A., Squassina A., de Mendonça A., Arias Pastor A., Kok A.A.L., Meggy A., Pastor A.B., Espinosa A., Corma-Gómez A., Martín Montes A., Sanabria Á., DeStefano A.L., Schneider A., Haapasalo A., Kinhult Ståhlbom A., Tybjærg-Hansen A., Hartmann A.M., Spottke A., Corbatón-Anchuelo A., Rongve A., Borroni B., Arosio B., Nacmias B., Nordestgaard B.G., Kunkle B.W., Charbonnier C., Abdelnour C., Masullo C., Martínez Rodríguez C., Muñoz-Fernandez C., Dufouil C., Graff C., Ferreira C.B., Chillotti C., Reynolds C.A., Fenoglio C., Van Broeckhoven C., Clark C., Pisanu C., Satizabal C.L., Holmes C., Buiza-Rueda D., Aarsland D., Rujescu D., Alcolea D., Galimberti D., Wallon D., Seripa D., Grünblatt E., Dardiotis E., Düzel E., Scarpini E., Conti E., Rubino E., Gelpi E., Rodriguez-Rodriguez E., Duron E., Boerwinkle E., Ferri E., Tagliavini F., Küçükali F., Pasquier F., Sanchez-Garcia F., Mangialasche F., Jessen F., Nicolas G., Selbæk G., Ortega G., Chêne G., Hadjigeorgiou G., Rossi G., Spalletta G., Giaccone G., Grande G., Binetti G., Papenberg G., Hampel H., Bailly H., Zetterberg H., Soininen H., Karlsson I.K., Alvarez I., Appollonio I., Giegling I., Skoog I., Saltvedt I., Rainero I., Rosas Allende I., Hort J., Diehl-Schmid J., Van Dongen J., Vidal J.-S., Lehtisalo J., Wiltfang J., Thomassen J.Q., Kornhuber J., Haines J.L., Vogelgsang J., Pineda J.A., Fortea J., Popp J., Deckert J., Buerger K., Morgan K., Fließbach K., Sleegers K., Molina-Porcel L., Kilander L., Weinhold L., Farrer L.A., Wang L.-S., Kleineidam L., Farotti L., Parnetti L., Tremolizzo L., Hausner L., Benussi L., Froelich L., Ikram M.A., Deniz-Naranjo M.C., Tsolaki M., Rosende-Roca M., Löwenmark M., Hulsman M., Spallazzi M., Pericak-Vance M.A., Esiri M., Bernal Sánchez-Arjona M., Dalmasso M.C., Martínez-Larrad M.T., Arcaro M., Nöthen M.M., Fernández-Fuertes M., Dichgans M., Ingelsson M., Herrmann M.J., Scherer M., Vyhnalek M., Kosmidis M.H., Yannakoulia M., Schmid M., Ewers M., Heneka M.T., Wagner M., Scamosci M., Kivipelto M., Hiltunen M., Zulaica M., Alegret M., Fornage M., Roberto N., van Schoor N.M., Seidu N.M., Banaj N., Armstrong N.J., Scarmeas N., Scherbaum N., Goldhardt O., Hanon O., Peters O., Skrobot O.A., Quenez O., Lerch O., Bossù P., Caffarra P., Dionigi Rossi P., Sakka P., Mecocci P., Hoffmann P., Holmans P.A., Fischer P., Riederer P., Yang Q., Marshall R., Kalaria R.N., Mayeux R., Vandenberghe R., Cecchetti R., Ghidoni R., Frikke-Schmidt R., Sorbi S., Hägg S., Engelborghs S., Helisalmi S., Botne Sando S., Kern S., Archetti S., Boschi S., Fostinelli S., Gil S., Mendoza S., Mead S., Ciccone S., Djurovic S., Heilmann-Heimbach S., Riedel-Heller S., Kuulasmaa T., del Ser T., Lebouvier T., Polak T., Ngandu T., Grimmer T., Bessi V., Escott-Price V., Giedraitis V., Deramecourt V., Maier W., Jian X., Pijnenburg Y.A.L., Smith A.D., Saenz A., Bizzarro A., Lauria A., Vacca A., Solomon A., Anastasiou A., Richardson A., Boland A., Koivisto A., Daniele A., Greco A., Marianthi A., McGuinness B., Fin B., Ferrari C., Custodero C., Ferrarese C., Ingino C., Mangone C., Reyes Toso C., Martínez C., Cuesta C., Muchnik C., Joachim C., Ortiz C., Besse C., Johansson C., Zoia C.P., Laske C., Anastasiou C., Palacio D.L., Politis D.G., Janowitz D., Craig D., Mann D.M., Neary D., Jürgen D., Daian D., Belezhanska D., Kohler E., Castaño E.M., Koutsouraki E., Chipi E., De Roeck E., Costantini E., Vardy E.R.L.C., Piras F., Roveta F., Piras F., Prestia F.A., Assogna F., Salani F., Sala G., Lacidogna G., Novack G., Wilcock G., Thonberg H., Kölsch H., Weber H., Boecker H., Etchepareborda I., Piaceri I., Tuomilehto J., Lindström J., Laczo J., Johnston J., Deleuze J.-F., Harris J., Schott J.M., Priller J., Bacha J.I., Snowden J., Lisso J., Mihova K.Y., Traykov L., Morelli L., Brusco L.I., Rainer M., Takalo M., Bjerke M., Del Zompo M., Serpente M., Sanchez Abalos M., Rios M., Peltonen M., Herrman M.J., Kohler M., Rojo M., Jones M., Orsini M., Medel N., Olivar N., Fox N.C., Salvadori N., Hooper N.M., Galeano P., Solis P., Bastiani P., Passmore P., Heun R., Antikainen R., Olaso R., Perneczky R., Germani S., López-García S., Love S., Mehrabian S., Bagnoli S., Kochen S., Andreoni S., Teipel S., Todd S., Pickering-Brown S., Natunen T., Tegos T., Laatikainen T., Strandberg T., Polvikoski T.M., Matoska V., Ciullo V., Cores V., Solfrizzi V., Lisetti V., Sevillano Z., Aguilera N., Alarcon E., Alegret M., Boada M., Buendia M., Cañabate P., Carracedo A., de Rojas I., Diego S., Espinosa A., Gailhajenet A., García-González P., Gil S., Guitart M., González-Pérez A., Hernández I., Ibarria M., Lafuente A., Macias J., Maroñas O., Martín E., Martínez M.T., Marquié M., Mauleón A., Moreno-Grau S., Moreno M., Orellana A., Ortega G., Pancho A., Pelejá E., Pineda J.A., Preckler S., Quintela I., Real L.M., Rosende-Roca M., Ruiz A., Sáez M.E., Sanabria A., Serrano-Rios M., Tárraga L., Valero S., Vargas L., Adarmes-Gómez A.D., Alonso M.D., Álvarez I., Álvarez V., Amer-Ferrer G., Antequera M., Antúnez C., Baquero M., Bernal M., Blesa R., Bullido M.J., Burguera J.A., Calero M., Carrillo F., Carrión-Claro M., Casajeros M.J., Clarimón J., Cruz-Gamero J.M., de Pancorbo M.M., de Rojas I., del Ser T., Diez-Fairen M., Escuela R., Garrote-Espina L., Fortea J., García-Alberca J.M., Garcia-Ribas G., Gómez-Garre P., Hevilla S., Jesús S., Labrador Espinosa M.A., Lage C., Legaz A., Lleó A., Lopez de Munain A., López-García S., Macias-García D., Manzanares S., Marín M., Marín-Muñoz J., Marín T., Marquié M., Martínez B., Martínez C., Martínez V., Martínez-Lage Álvarez P., Medina M., Mendioroz Iriarte M., Menéndez-González M., Mir P., Molinuevo J.L., Pastor P., Pérez Tur J., Periñán-Tocino T., Pineda-Sanchez R., Piñol-Ripoll G., Rábano A., Real de Asúa D., Rodrigo S., Rodríguez-Rodríguez E., Royo J.L., Sanchez del Valle Díaz R., Sánchez-Juan P., Sastre I., Vicente M.P., Vigo-Ortega R., Vivancos L., Macleod C., McCracken C., Brayne C., Bresner C., Grozeva D., Bellou E., Sommerville E.W., Matthews F., Leonenko G., Menzies G., Windle G., Harwood J., Phillips J., Bennett K., Luckuck L., Clare L., Woods R., Saad S., Burholt V., Rongve A., Kehoe P.G., Sánchez-Juan P., Pastor P., Pérez-Tur J., Piñol-Ripoll G., Lopez de Munain A., Bullido M.J., Álvarez V., Lleó A., Real L.M., Mir P., Medina M., Scheltens P., Holstege H., Marquié M., Sáez M.E., Carracedo Á., Amouyel P., Schellenberg G.D., Williams J., Seshadri S., van Duijn C.M., Mather K.A., Sánchez-Valle R., Serrano-Ríos M., Orellana A., Tárraga L., Blennow K., Huisman M., Andreassen O.A., Posthuma D., Clarimón J., Boada M., van der Flier W.M., Ramirez A., Lambert J.-C., van der Lee S.J., Ruiz A
Increased circulating insulin-like growth factor-1 in late-onset Alzheimer's disease
No full textBackground: Insulin-like growth factor (IGF)-1 has been implicated in the pathogenesis of Alzheimer's disease ( AD).
Methods: We compared the level of circulating total and bioavailable IGF-1, by simultaneous measurements of IGF-1 and IGF binding protein ( IGFBP)-3, between 87 patients diagnosed with AD and 126 age and sex matched control subjects without cognitive impairment. Blood samples were collected and IGF-1 and IGFBP-3 measured by ELISA. Subjects were also genotyped for apolipoprotein E.
Results: Total circulating IGF-1 levels were significantly raised in the AD group as compared to the control group (p = 0.022). There was no significant difference in the circulating level of IGFBP-3 between the two groups. When the IGF-1 levels were ratioed against IGFBP-3 levels as an indicator of unbound, bioavailable circulating IGF-1, there was a significant increase in the molar IGF-1:IGFBP-3 ratio in the AD subjects (0.181 +/- 0.006) as compared to the controls (0.156 +/- 0.004) (p < 0.001). Logistic regression analysis revealed that an increase in the IGF-1: IGFBP-3 molar ratio increased the risk of AD significantly.
Conclusion: The results of increased total and free circulating IGF-1 support the hypothesis that in its early stages late-onset AD reflects a state of resistance to IGF-1
New horizons in the role of digital data in the healthcare of older people
No full textThere are national and global moves to improve effective digital data design and application in healthcare. This New Horizons commentary describes the role of digital data in healthcare of the ageing population. We outline how health and social care professionals can engage in the proactive design of digital systems that appropriately serve people as they age, carers and the workforce that supports them.
Key Points
Healthcare improvements have resulted in increased population longevity and hence multimorbidity.
Shared care records to improve communication and information continuity across care settings hold potential for older people.
Data structure and coding are key considerations.
A workforce with expertise in caring for older people with relevant knowledge and skills in digital healthcare is important
New horizons in the role of digital data in the healthcare of older people
No full textThere are national and global moves to improve effective digital data design and application in healthcare. This New Horizons commentary describes the role of digital data in healthcare of the ageing population. We outline how health and social care professionals can engage in the proactive design of digital systems that appropriately serve people as they age, carers and the workforce that supports them. KEY POINTS: Healthcare improvements have resulted in increased population longevity and hence multimorbidity. Shared care records to improve communication and information continuity across care settings hold potential for older people. Data structure and coding are key considerations. A workforce with expertise in caring for older people with relevant knowledge and skills in digital healthcare is important.Published version, accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
No full textSupported by national grant from the Instituto de Salud Carlos III FI20/00215 (…); M.B. and A.R. are also supported by Spanish national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301.Rojas, I. de, Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I.E., Pedersen, N.L., Stringa, N., Zettergren, A., Hernández, I., Montrreal, L., Antúnez, C., Antonell, A., Tankard, R.M., Bis, J.C., Sims, R., Bellenguez, C., Quintela, I., González-Perez, A., Calero, M., Franco-Macías, E., Macías, J., Blesa, R., Cervera-Carles, L., Menéndez-González, M., Frank-García, A., Royo, J.L., Moreno, F., Huerto Vilas, R., Baquero, M., Diez-Fairen, M., Lage, C., García-Madrona, S., García-González, P., Alarcón-Martín, E., Valero, S., Sotolongo-Grau, O., Ullgren, A., Naj, A.C., Lemstra, A.W., Benaque, A., Pérez-Cordón, A., Benussi, A., Rábano, A., Padovani, A., Squassina, A., de Mendonça, A., Arias Pastor, A., Kok, A.A.L., Meggy, A., Pastor, A.B., Espinosa, A., Corma-Gómez, A., Martín Montes, A., Sanabria, Á., DeStefano, A.L., Schneider, A., Haapasalo, A., Kinhult Ståhlbom, A., Tybjærg-Hansen, A., Hartmann, A.M., Spottke, A., Corbatón-Anchuelo, A., Rongve, A., Borroni, B., Arosio, B., Nacmias, B., Nordestgaard, B.G., Kunkle, B.W., Charbonnier, C., Abdelnour, C., Masullo, C., Martínez Rodríguez, C., Muñoz-Fernandez, C., Dufouil, C., Graff, C., Ferreira, C.B., Chillotti, C., Reynolds, C.A., Fenoglio, C., Van Broeckhoven, C., Clark, C., Pisanu, C., Satizabal, C.L., Holmes, C., Buiza-Rueda, D., Aarsland, D., Rujescu, D., Alcolea, D., Galimberti, D., Wallon, D., Seripa, D., Grünblatt, E., Dardiotis, E., Düzel, E., Scarpini, E., Conti, E., Rubino, E., Gelpi, E., Rodriguez-Rodriguez, E., Duron, E., Boerwinkle, E., Ferri, E., Tagliavini, F., Küçükali, F., Pasquier, F., Sanchez-Garcia, F., Mangialasche, F., Jessen, F., Nicolas, G., Selbæk, G., Ortega, G., Chêne, G., Hadjigeorgiou, G., Rossi, G., Spalletta, G., Giaccone, G., Grande, G., Binetti, G., Papenberg, G., Hampel, H., Bailly, H., Zetterberg, H., Soininen, H., Karlsson, I.K., Alvarez, I., Appollonio, I., Giegling, I., Skoog, I., Saltvedt, I., Rainero, I., Rosas Allende, I., Hort, J., Diehl-Schmid, J., Van Dongen, J., Vidal, J.-S., Lehtisalo, J., Wiltfang, J., Thomassen, J.Q., Kornhuber, J., Haines, J.L., Vogelgsang, J., Pineda, J.A., Fortea, J., Popp, J., Deckert, J., Buerger, K., Morgan, K., Fließbach, K., Sleegers, K., Molina-Porcel, L., Kilander, L., Weinhold, L., Farrer, L.A., Wang, L.-S., Kleineidam, L., Farotti, L., Parnetti, L., Tremolizzo, L., Hausner, L., Benussi, L., Froelich, L., Ikram, M.A., Deniz-Naranjo, M.C., Tsolaki, M., Rosende-Roca, M., Löwenmark, M., Hulsman, M., Spallazzi, M., Pericak-Vance, M.A., Esiri, M., Bernal Sánchez-Arjona, M., Dalmasso, M.C., Martínez-Larrad, M.T., Arcaro, M., Nöthen, M.M., Fernández-Fuertes, M., Dichgans, M., Ingelsson, M., Herrmann, M.J., Scherer, M., Vyhnalek, M., Kosmidis, M.H., Yannakoulia, M., Schmid, M., Ewers, M., Heneka, M.T., Wagner, M., Scamosci, M., Kivipelto, M., Hiltunen, M., Zulaica, M., Alegret, M., Fornage, M., Roberto, N., van Schoor, N.M., Seidu, N.M., Banaj, N., Armstrong, N.J., Scarmeas, N., Scherbaum, N., Goldhardt, O., Hanon, O., Peters, O., Skrobot, O.A., Quenez, O., Lerch, O., Bossù, P., Caffarra, P., Dionigi Rossi, P., Sakka, P., Hoffmann, P., Holmans, P.A., Fischer, P., Riederer, P., Yang, Q., Marshall, R., Kalaria, R.N., Mayeux, R., Vandenberghe, R., Cecchetti, R., Ghidoni, R., Frikke-Schmidt, R., Sorbi, S., Hägg, S., Engelborghs, S., Helisalmi, S., Botne Sando, S., Kern, S., Archetti, S., Boschi, S., Fostinelli, S., Gil, S., Mendoza, S., Mead, S., Ciccone, S., Djurovic, S., Heilmann-Heimbach, S., Riedel-Heller, S., Kuulasmaa, T., del Ser, T., Lebouvier, T., Polak, T., Ngandu, T., Grimmer, T., Bessi, V., Escott-Price, V., Giedraitis, V., Deramecourt, V., Maier, W., Jian, X., Pijnenburg, Y.A.L., Smith, A.D., Saenz, A., Bizzarro, A., Lauria, A., Vacca, A., Solomon, A., Anastasiou, A., Richardson, A., Boland, A., Koivisto, A., Daniele, A., Greco, A., Marianthi, A., McGuinness, B., Fin, B., Ferrari, C., Custodero, C., Ferrarese, C., Ingino, C., Mangone, C., Reyes Toso, C., Martínez, C., Cuesta, C., Muchnik, C., Joachim, C., Ortiz, C., Besse, C., Johansson, C., Zoia, C.P., Laske, C., Anastasiou, C., Palacio, D.L., Politis, D.G., Janowitz, D., Craig, D., Mann, D.M., Neary, D., Jürgen, D., Daian, D., Belezhanska, D., Kohler, E., Castaño, E.M., Koutsouraki, E., Chipi, E., De Roeck, E., Costantini, E., Vardy, E.R.L.C., Piras, F., Roveta, F., Piras, F., Prestia, F.A., Assogna, F., Salani, F., Sala, G., Lacidogna, G., Novack, G., Wilcock, G., Thonberg, H., Kölsch, H., Weber, H., Boecker, H., Etchepareborda, I., Piaceri, I., Tuomilehto, J., Lindström, J., Laczo, J., Johnston, J., Deleuze, J.-F., Harris, J., Schott, J.M., Priller, J., Bacha, J.I., Snowden, J., Lisso, J., Mihova, K.Y., Traykov, L., Morelli, L., Brusco, L.I., Rainer, M., Takalo, M., Bjerke, M., Del Zompo, M., Serpente, M., Sanchez Abalos, M., Rios, M., Peltonen, M., Herrman, M.J., Kosmidis, M.H., Kohler, M., Rojo, M., Jones, M., Orsini, M., Medel, N., Olivar, N., Fox, N.C., Salvadori, N., Hooper, N.M., Galeano, P., Solis, P., Bastiani, P., Mecocci, P., Passmore, P., Heun, R., Antikainen, R., Olaso, R., Perneczky, R., Germani, S., López-García, S., Love, S., Mehrabian, S., Bagnoli, S., Kochen, S., Andreoni, S., Teipel, S., Todd, S., Pickering-Brown, S., Natunen, T., Tegos, T., Laatikainen, T., Strandberg, T., Polvikoski, T.M., Matoska, V., Ciullo, V., Cores, V., Solfrizzi, V., Lisetti, V., Sevillano, Z., Abdelnour, C., Aguilera, N., Alarcon, E., Alegret, M., Benaque, A., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., Corbatón-Anchuelo, A., Diego, S., Espinosa, A., Gailhajenet, A., Gil, S., Guitart, M., Hernández, I., Ibarria, M., Lafuente, A., Macias, J., Maroñas, O., Martín, E., Martínez, M.T., Marquié, M., Mauleón, A., Montrreal, L., Moreno-Grau, S., Moreno, M., Orellana, A., Ortega, G., Pancho, A., Pelejá, E., Pérez-Cordon, A., Pineda, J.A., Preckler, S., Quintela, I., Real, L.M., Rosende-Roca, M., Ruiz, A., Sáez, M.E., Sanabria, A., Serrano-Rios, M., Sotolongo-Grau, O., Tárraga, L., Valero, S., Vargas, L., Adarmes-Gómez, A.D., Alarcón-Martín, E., Alonso, M.D., Álvarez, I., Álvarez, V., Amer-Ferrer, G., Antequera, M., Antúnez, C., Baquero, M., Bernal, M., Blesa, R., Boada, M., Buiza-Rueda, D., Bullido, M.J., Burguera, J.A., Calero, M., Carrillo, F., Carrión-Claro, M., Casajeros, M.J., Clarimón, J., Cruz-Gamero, J.M., de Pancorbo, M.M., del Ser, T., Diez-Fairen, M., Escuela, R., Garrote-Espina, L., Fortea, J., Franco-Macías, E., Frank-García, A., García-Alberca, J.M., Garcia Madrona, S., Garcia-Ribas, G., Gómez-Garre, P., Hernández, I., Hevilla, S., Jesús, S., Labrador Espinosa, M.A., Lage, C., Legaz, A., Lleó, A., Lopez de Munain, A., López-García, S., Macias-García, D., Manzanares, S., Marín, M., Marín-Muñoz, J., Marín, T., Marquié, M., Martín Montes, A., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Mir, P., Molinuevo, J.L., Pastor, P., Pérez Tur, J., Periñán-Tocino, T., Pineda-Sanchez, R., Piñol-Ripoll, G., Rábano, A., Real de Asúa, D., Rodrigo, S., Rodríguez-Rodríguez, E., Royo, J.L., Ruiz, A., Sanchez del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Valero, S., Vicente, M.P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, C., Bresner, C., Grozeva, D., Bellou, E., Sommerville, E.W., Matthews, F., Leonenko, G., Menzies, G., Windle, G., Harwood, J., Phillips, J., Bennett, K., Luckuck, L., Clare, L., Woods, R., Saad, S., Burholt, V., Jansen, I.E., Rongve, A., Kehoe, P.G., Garcia-Ribas, G., Sánchez-Juan, P., Pastor, P., Pérez-Tur, J., Piñol-Ripoll, G., Lopez de Munain, A., García-Alberca, J.M., Bullido, M.J., Álvarez, V., Lleó, A., Real, L.M., Medina, M., Scheltens, P., Holstege, H., Marquié, M., Sáez, M.E., Carracedo, Á., Amouyel, P., Schellenberg, G.D., Williams, J., Seshadri, S., van Duijn, C.M., Mather, K.A., Sánchez-Valle, R., Serrano-Ríos, M., Orellana, A., Tárraga, L., Blennow, K., Huisman, M., Andreassen, O.A., Posthuma, D., Clarimón, J., Boada, M., van der Flier, W.M., Ramirez, A., Lambert, J.-C., van der Lee, S.J., Ruiz, A., EADB contributors, The GR@ACE study group, DEGESCO consortium, IGAP (ADGC, CHARGE, EADI, GERAD), PGC-ALZ consorti
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
No full textGenetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s)
Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease
No full textWe sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P = 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).<br/
