van der Lee, Sven J., Conway, Olivia J., Jansen, Iris, Carrasquillo, Minerva M., Kleineidam, Luca, van den Akker, Erik, Hernandez, Isabel, van Eijk, Kristel R., Stringa, Najada ORCID: 0000-0001-6350-452X, Chen, Jason A., Zettergren, Anna, Andlauer, Till F. M., Diez-Fairen, Monica ORCID: 0000-0003-1882-0309, Simon-Sanchez, Javier, Lleo, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E., Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael ORCID: 0000-0003-2589-6440, Fortea, Juan, Keogh, Michael J., Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A. ORCID: 0000-0001-6380-2420, Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar ORCID: 0000-0002-2148-381X, Riedel-Heller, Steffi, Illan-Gala, Ignacio ORCID: 0000-0002-5418-2052, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Bergh, Florian Then, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M., Indakoetxea, Begona, Collij, Lyduine E., Scherer, Martin, Morenas-Rodriguez, Estrella, Ironside, James W., van Berckel, Bart N. M., Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L., Pastor, Pau ORCID: 0000-0002-7493-8777, Rodriguez Rodriguez, Eloy, Boeve, Bradley F., Petersen, Ronald C., Ferman, Tanis J., van Gerpen, Jay A., Reinders, Marcel J. T., Uitti, Ryan J., Tarraga, Lluis, Maier, Wolfgang, Dols-Icardo, Oriol ORCID: 0000-0003-2656-8748, Kawalia, Amit, Dalmasso, Maria Carolina ORCID: 0000-0002-4901-9955, Boada, Merce, Zettl, Uwe K., van Schoor, Natasja M., Beekman, Marian, Allen, Mariet, Masliah, Eliezer, Lopez de Munain, Adolfo, Pantelyat, Alexander, Wszolek, Zbigniew K., Ross, Owen A., Dickson, Dennis W., Graff-Radford, Neill R., Knopman, David, Rademakers, Rosa, Lemstra, Afina W., Pijnenburg, Yolande A. L., Scheltens, Philip ORCID: 0000-0002-1046-6408, Gasser, Thomas, Chinnery, Patrick F., Hemmer, Bernhard, Huisman, Martijn A., Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A., Sorensen, Thorkild I. A., Heutink, Peter ORCID: 0000-0001-5218-1737, Sanchez-Juan, Pascual, Posthuma, Danielle, Clarimon, Jordi, Christensen, Kaare ORCID: 0000-0002-5429-5292, Ertekin-Taner, Nilufer, Scholz, Sonja W. ORCID: 0000-0002-6623-0429, Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Ruiz, Agustin, Slagboom, Eline, van der Flier, Wiesje M. and Holstege, Henne
(2019).
A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.
Acta Neuropathol., 138 (2).
S. 237 - 251.
NEW YORK:
SPRINGER.
ISSN 1432-0533
Full text not available from this repository.
Abstract
The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC gamma 2 pathway as drug-target.
Item Type: |
Journal Article
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Creators: |
Creators | Email | ORCID | ORCID Put Code |
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van der Lee, Sven J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Conway, Olivia J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Jansen, Iris | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Carrasquillo, Minerva M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Kleineidam, Luca | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van den Akker, Erik | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hernandez, Isabel | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van Eijk, Kristel R. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Stringa, Najada | UNSPECIFIED | orcid.org/0000-0001-6350-452X | UNSPECIFIED | Chen, Jason A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Zettergren, Anna | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Andlauer, Till F. M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Diez-Fairen, Monica | UNSPECIFIED | orcid.org/0000-0003-1882-0309 | UNSPECIFIED | Simon-Sanchez, Javier | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lleo, Alberto | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Zetterberg, Henrik | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Nygaard, Marianne | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Blauwendraat, Cornelis | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Savage, Jeanne E. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Mengel-From, Jonas | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Moreno-Grau, Sonia | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wagner, Michael | UNSPECIFIED | orcid.org/0000-0003-2589-6440 | UNSPECIFIED | Fortea, Juan | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Keogh, Michael J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Blennow, Kaj | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Skoog, Ingmar | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Friese, Manuel A. | UNSPECIFIED | orcid.org/0000-0001-6380-2420 | UNSPECIFIED | Pletnikova, Olga | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Zulaica, Miren | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lage, Carmen | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | de Rojas, Itziar | UNSPECIFIED | orcid.org/0000-0002-2148-381X | UNSPECIFIED | Riedel-Heller, Steffi | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Illan-Gala, Ignacio | UNSPECIFIED | orcid.org/0000-0002-5418-2052 | UNSPECIFIED | Wei, Wei | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Jeune, Bernard | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Orellana, Adelina | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Bergh, Florian Then | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wang, Xue | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hulsman, Marc | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Beker, Nina | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Tesi, Niccolo | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Morris, Christopher M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Indakoetxea, Begona | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Collij, Lyduine E. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Scherer, Martin | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Morenas-Rodriguez, Estrella | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Ironside, James W. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van Berckel, Bart N. M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Alcolea, Daniel | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wiendl, Heinz | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Strickland, Samantha L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Pastor, Pau | UNSPECIFIED | orcid.org/0000-0002-7493-8777 | UNSPECIFIED | Rodriguez Rodriguez, Eloy | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Boeve, Bradley F. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Petersen, Ronald C. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Ferman, Tanis J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van Gerpen, Jay A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Reinders, Marcel J. T. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Uitti, Ryan J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Tarraga, Lluis | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Maier, Wolfgang | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dols-Icardo, Oriol | UNSPECIFIED | orcid.org/0000-0003-2656-8748 | UNSPECIFIED | Kawalia, Amit | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dalmasso, Maria Carolina | UNSPECIFIED | orcid.org/0000-0002-4901-9955 | UNSPECIFIED | Boada, Merce | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Zettl, Uwe K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van Schoor, Natasja M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Beekman, Marian | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Allen, Mariet | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Masliah, Eliezer | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lopez de Munain, Adolfo | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Pantelyat, Alexander | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Wszolek, Zbigniew K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Ross, Owen A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Dickson, Dennis W. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Graff-Radford, Neill R. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Knopman, David | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Rademakers, Rosa | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Lemstra, Afina W. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Pijnenburg, Yolande A. L. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Scheltens, Philip | UNSPECIFIED | orcid.org/0000-0002-1046-6408 | UNSPECIFIED | Gasser, Thomas | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Chinnery, Patrick F. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Hemmer, Bernhard | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Huisman, Martijn A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Troncoso, Juan | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Moreno, Fermin | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Nohr, Ellen A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Sorensen, Thorkild I. A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Heutink, Peter | UNSPECIFIED | orcid.org/0000-0001-5218-1737 | UNSPECIFIED | Sanchez-Juan, Pascual | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Posthuma, Danielle | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Clarimon, Jordi | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Christensen, Kaare | UNSPECIFIED | orcid.org/0000-0002-5429-5292 | UNSPECIFIED | Ertekin-Taner, Nilufer | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Scholz, Sonja W. | UNSPECIFIED | orcid.org/0000-0002-6623-0429 | UNSPECIFIED | Ramirez, Alfredo | UNSPECIFIED | orcid.org/0000-0003-4991-763X | UNSPECIFIED | Ruiz, Agustin | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Slagboom, Eline | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | van der Flier, Wiesje M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED | Holstege, Henne | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
URN: |
urn:nbn:de:hbz:38-133815 |
DOI: |
10.1007/s00401-019-02026-8 |
Journal or Publication Title: |
Acta Neuropathol. |
Volume: |
138 |
Number: |
2 |
Page Range: |
S. 237 - 251 |
Date: |
2019 |
Publisher: |
SPRINGER |
Place of Publication: |
NEW YORK |
ISSN: |
1432-0533 |
Language: |
English |
Faculty: |
Faculty of Management, Economy and Social Sciences |
Divisions: |
Unspecified |
Subjects: |
no entry |
Uncontrolled Keywords: |
Keywords | Language |
---|
GENOME-WIDE ASSOCIATION; PHOSPHOLIPASE-C-GAMMA; GENETIC ARCHITECTURE; INNATE IMMUNITY; ACTIVATION; APOE; AUTOIMMUNITY; INFLAMMATION; REPLICATION; MECHANISMS | Multiple languages | Clinical Neurology; Neurosciences; Pathology | Multiple languages |
|
Refereed: |
Yes |
URI: |
http://kups.ub.uni-koeln.de/id/eprint/13381 |
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