Genome-Wide Meta-Analysis of Cerebrospinal Fluid Biomarkers in Alzheimer's Disease and Parkinson's Disease Cohorts

被引：6

作者：

Ta, Michael ^{[1
,2
,3
,4
]}

Blauwendraat, Cornelis ^{[1
,3
,4
]}

Antar, Tarek ^{[1
,3
,4
]}

Leonard, Hampton L. ^{[1
,2
,3
,4
]}

Singleton, Andrew B. ^{[1
,3
,4
]}

Nalls, Mike A. ^{[1
,2
,3
,4
]}

Iwaki, Hirotaka ^{[1
,2
,3
,4
]}

机构：

[1] NIA, Lab Neurogenet, NIH, Bethesda, MD USA

[2] Data Tecn Int, Washington, DC USA

[3] NIA, Ctr Alzheimers & Related Dementias, Bethesda, MD USA

[4] NINDS, NIH, Bethesda, MD USA

来源：

MOVEMENT DISORDERS | 2023年 / 38卷 / 09期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

Parkinson's disease; Alzheimer's disease; genome-wide association study; longitudinal GWAS; ALPHA-SYNUCLEIN; LONGITUDINAL ASSESSMENT; COGNITIVE DECLINE; AMYLOID-BETA; TAU; ASSOCIATION; LOCI; INSIGHTS; RISK; GWAS;

D O I：

10.1002/mds.29511

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

BackgroundAmyloid-& beta;, phosphorylated tau (p-tau), and total tau (t-tau) in cerebrospinal fluid are established biomarkers for Alzheimer's disease (AD). In other neurodegenerative diseases, such as Parkinson's disease (PD), these biomarkers have also been found to be altered, and the molecular mechanisms responsible for these alterations are still under investigation. Moreover, the interplay between these mechanisms and the diverse underlying disease states remains to be elucidated. ObjectiveTo investigate genetic contributions to the AD biomarkers and assess the commonality and heterogeneity of the associations per underlying disease status. MethodsWe conducted genome-wide association studies (GWASs) for the AD biomarkers on subjects from the Parkinson's Progression Markers Initiative, the Fox Investigation for New Discovery of Biomarkers, and the Alzheimer's Disease Neuroimaging Initiative, and meta-analyzed with the largest AD GWAS. We tested heterogeneity of associations of interest between different disease statuses (AD, PD, and control). ResultsWe observed three GWAS signals: the APOE locus for amyloid-& beta;, the 3q28 locus between GEMC1 and OSTN for p-tau and t-tau, and the 7p22 locus (top hit: rs60871478, an intronic variant for DNAAF5, also known as HEATR2) for p-tau. The 7p22 locus is novel and colocalized with the brain DNAAF5 expression. Although no heterogeneity from underlying disease status was observed for the earlier GWAS signals, some disease risk loci suggested disease-specific associations with these biomarkers. ConclusionsOur study identified a novel association at the intronic region of DNAAF5 associated with increased levels of p-tau across all diseases. We also observed some disease-specific genetic associations with these biomarkers. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

引用

页码：1697 / 1705

页数：9

共 37 条

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Ghetti, Bernardino ;

Martins, Ralph N. ;

Masters, Colin L. ;

Mayeux, Richard ;

Ringman, John M. ;

Rossor, Martin N. ;

Salloway, Stephen ;

Schofield, Peter R. ;

Sperling, Reisa A. ;

Marcus, Daniel ;

Cairns, Nigel J. ;

Buckles, Virginia D. ;

Ladenson, Jack H. ;

Morris, John C. ;

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Schellenberg, Gerard D. ;

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Hansson, Oskar ;

Seibyl, John ;

Stomrud, Erik ;

Zetterberg, Henrik ;

Trojanowski, John Q. ;

Bittner, Tobias ;

Lifke, Valeria ;

Corradini, Veronika ;

Eichenlaub, Udo ;

Batrla, Richard ;

Buck, Katharina ;

Zink, Katharina ;

Rabe, Christina ;

Blennow, Kaj ;

Shaw, Leslie M. .

ALZHEIMERS & DEMENTIA, 2018, 14 (11) :1470-1481

← 1 2 3 4 →

共 37 条

[1] Human whole genome genotype and transcriptome data for Alzheimer's and other neurodegenerative diseases [J].

Allen, Mariet ;

Carrasquillo, Minerva M. ;

Funk, Cory ;

Heavner, Benjamin D. ;

Zou, Fanggeng ;

Younkin, Curtis S. ;

Burgess, Jeremy D. ;

Chai, High-Seng ;

Crook, Julia ;

Eddy, James A. ;

Li, Hongdong ;

Logsdon, Ben ;

Peters, Mette A. ;

Dang, Kristen K. ;

Wang, Xue ;

Serie, Daniel ;

Wang, Chen ;

Thuy Nguyen ;

Lincoln, Sarah ;

Malphrus, Kimberly ;

Bisceglio, Gina ;

Li, Ma ;

Golde, Todd E. ;

Mangravite, Lara M. ;

Asmann, Yan ;

Price, Nathan D. ;

Petersen, Ronald C. ;

Graff-Radford, Neill R. ;

Dickson, Dennis W. ;

Younkin, Steven G. ;

Ertekin-Taner, Nilufer .

SCIENTIFIC DATA, 2016, 3

[2] Integrating common and rare genetic variation in diverse human populations [J].

Altshuler, David M. ;

Gibbs, Richard A. ;

Peltonen, Leena ;

Dermitzakis, Emmanouil ;

Schaffner, Stephen F. ;

Yu, Fuli ;

Bonnen, Penelope E. ;

de Bakker, Paul I. W. ;

Deloukas, Panos ;

Gabriel, Stacey B. ;

Gwilliam, Rhian ;

Hunt, Sarah ;

Inouye, Michael ;

Jia, Xiaoming ;

Palotie, Aarno ;

Parkin, Melissa ;

Whittaker, Pamela ;

Chang, Kyle ;

Hawes, Alicia ;

Lewis, Lora R. ;

Ren, Yanru ;

Wheeler, David ;

Muzny, Donna Marie ;

Barnes, Chris ;

Darvishi, Katayoon ;

Hurles, Matthew ;

Korn, Joshua M. ;

Kristiansson, Kati ;

Lee, Charles ;

McCarroll, Steven A. ;

Nemesh, James ;

Keinan, Alon ;

Montgomery, Stephen B. ;

Pollack, Samuela ;

Price, Alkes L. ;

Soranzo, Nicole ;

Gonzaga-Jauregui, Claudia ;

Anttila, Verneri ;

Brodeur, Wendy ;

Daly, Mark J. ;

Leslie, Stephen ;

McVean, Gil ;

Moutsianas, Loukas ;

Nguyen, Huy ;

Zhang, Qingrun ;

Ghori, Mohammed J. R. ;

McGinnis, Ralph ;

McLaren, William ;

Takeuchi, Fumihiko ;

Grossman, Sharon R. .

NATURE, 2010, 467 (7311) :52-58

[3] New insights into the genetic etiology of Alzheimer's disease and related dementias [J].

Bellenguez, Celine ;

Kucukali, Fahri ;

Jansen, Iris E. ;

Kleineidam, Luca ;

Moreno-Grau, Sonia ;

Amin, Najaf ;

Naj, Adam C. ;

Campos-Martin, Rafael ;

Grenier-Boley, Benjamin ;

Andrade, Victor ;

Holmans, Peter A. ;

Boland, Anne ;

Damotte, Vincent ;

van der Lee, Sven J. ;

Costa, Marcos R. ;

Kuulasmaa, Teemu ;

Yang, Qiong ;

De Rojas, Itziar ;

Bis, Joshua C. ;

Yaqub, Amber ;

Prokic, Ivana ;

Chapuis, Julien ;

Ahmad, Shahzad ;

Giedraitis, Vilmantas ;

Aarsland, Dag ;

Garcia-Gonzalez, Pablo ;

Abdelnour, Carla ;

Alarcon-Martin, Emilio ;

Alcolea, Daniel ;

Alegret, Montserrat ;

Alvarez, Ignacio ;

Alvarez, Victoria ;

Armstrong, Nicola J. ;

Tsolaki, Anthoula ;

Antunez, Carmen ;

Appollonio, Ildebrando ;

Arcaro, Marina ;

Archetti, Silvana ;

Arias Pastor, Alfonso ;

Arosio, Beatrice ;

Athanasiu, Lavinia ;

Bailly, Henri ;

Banaj, Nerisa ;

Baquero, Miquel ;

Barral, Sandra ;

Beiser, Alexa ;

Pastor, Ana Belen ;

Below, Jennifer E. ;

Benchek, Penelope ;

Benussi, Luisa .

NATURE GENETICS, 2022, 54 (04) :412-436

[4] A Review of Fluid Biomarkers for Alzheimer’s Disease: Moving from CSF to Blood [J].

Blennow K. .

Neurology and Therapy, 2017, 6 (Suppl 1) :15-24

[5] GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer's Disease [J].

Cruchaga, Carlos ;

Kauwe, John S. K. ;

Harari, Oscar ;

Jin, Sheng Chih ;

Cai, Yefei ;

Karch, Celeste M. ;

Benitez, Bruno A. ;

Jeng, Amanda T. ;

Skorupa, Tara ;

Carrell, David ;

Bertelsen, Sarah ;

Bailey, Matthew ;

McKean, David ;

Shulman, Joshua M. ;

De Jager, Philip L. ;

Chibnik, Lori ;

Bennett, David A. ;

Arnold, Steve E. ;

Harold, Denise ;

Sims, Rebecca ;

Gerrish, Amy ;

Williams, Julie ;

Van Deerlin, Vivianna M. ;

Lee, Virginia M. -Y. ;

Shaw, Leslie M. ;

Trojanowski, John Q. ;

Haines, Jonathan L. ;

Mayeux, Richard ;

Pericak-Vance, Margaret A. ;

Farrer, Lindsay A. ;

Schellenberg, Gerard D. ;

Peskind, Elaine R. ;

Galasko, Douglas ;

Fagan, Anne M. ;

Holtzman, David M. ;

Morris, John C. ;

Goate, Alison M. .

NEURON, 2013, 78 (02) :256-268

[6] Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers [J].

Deming, Yuetiva ;

Li, Zeran ;

Kapoor, Manav ;

Harari, Oscar ;

Del-Aguila, Jorge L. ;

Black, Kathleen ;

Carrell, David ;

Cai, Yefei ;

Fernandez, Maria Victoria ;

Budde, John ;

Ma, Shengmei ;

Saef, Benjamin ;

Howells, Bill ;

Huang, Kuan-lin ;

Bertelsen, Sarah ;

Fagan, Anne M. ;

Holtzman, David M. ;

Morris, John C. ;

Kim, Sungeun ;

Saykin, Andrew J. ;

De Jager, Philip L. ;

Albert, Marilyn ;

Moghekar, Abhay ;

O'Brien, Richard ;

Riemenschneider, Matthias ;

Petersen, Ronald C. ;

Blennow, Kaj ;

Zetterberg, Henrik ;

Minthon, Lennart ;

Van Deerlin, Vivianna M. ;

Lee, Virginia Man-Yee ;

Shaw, Leslie M. ;

Trojanowski, John Q. ;

Schellenberg, Gerard ;

Haines, Jonathan L. ;

Mayeux, Richard ;

Pericak-Vance, Margaret A. ;

Farrer, Lindsay A. ;

Peskind, Elaine R. ;

Li, Ge ;

Di Narzo, Antonio F. ;

Kauwe, John S. K. ;

Goate, Alison M. ;

Cruchaga, Carlos .

ACTA NEUROPATHOLOGICA, 2017, 133 (05) :839-856

[7] Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 [J].

Dorsey, E. Ray ;

Elbaz, Alexis ;

Nichols, Emma ;

Abd-Allah, Foad ;

Abdelalim, Ahmed ;

Adsuar, Jose C. ;

Ansha, Mustafa Geleto ;

Brayne, Carol ;

Choi, Jee-Young J. ;

Collado-Mateo, Daniel ;

Dahodwala, Nabila ;

Huyen Phuc Do ;

Edessa, Dumessa ;

Endres, Matthias ;

Fereshtehnejad, Seyed-Mohammad ;

Foreman, Kyle J. ;

Gbetoho Gankpe, Fortune ;

Gupta, Rahul ;

Hankey, Graeme J. ;

Hay, Simon I. ;

Hegazy, Mohamed I. ;

Hibstu, Desalegn T. ;

Kasaeian, Amir ;

Khader, Yousef ;

Khalil, Ibrahim ;

Khang, Young-Ho ;

Kim, Yun Jin ;

Kokubo, Yoshihiro ;

Logroscino, Giancarlo ;

Massano, Joao ;

Ibrahim, Norlinah Mohamed ;

Mohammed, A. Mohammed ;

Mohammadi, Alireza ;

Moradi-Lakeh, Maziar ;

Naghavi, Mohsen ;

Binh Thanh Nguyen ;

Nirayo, Yirga Legesse ;

Ogbo, Felix Akpojene ;

Owolabi, Mayowa Ojo ;

Pereira, David M. ;

Postma, Maarten J. ;

Qorbani, Mostafa ;

Rahman, Muhammad Aziz ;

Roba, Kedir T. ;

Safari, Hosein ;

Safiri, Saeid ;

Satpathy, Maheswar ;

Sawhney, Monika ;

Shafieesabet, Azadeh ;

Shiferaw, Mekonnen Sisay .

LANCET NEUROLOGY, 2018, 17 (11) :939-953

[8] Longitudinal Change in CSF Biomarkers in Autosomal-Dominant Alzheimer's Disease [J].

Fagan, Anne M. ;

Xiong, Chengjie ;

Jasielec, Mateusz S. ;

Bateman, Randall J. ;

Goate, Alison M. ;

Benzinger, Tammie L. S. ;

Ghetti, Bernardino ;

Martins, Ralph N. ;

Masters, Colin L. ;

Mayeux, Richard ;

Ringman, John M. ;

Rossor, Martin N. ;

Salloway, Stephen ;

Schofield, Peter R. ;

Sperling, Reisa A. ;

Marcus, Daniel ;

Cairns, Nigel J. ;

Buckles, Virginia D. ;

Ladenson, Jack H. ;

Morris, John C. ;

Holtzman, David M. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (226)

[9] Genome-wide association reveals genetic effects on human Aβ42 and τ protein levels in cerebrospinal fluids: a case control study [J].

Han, Mi-Ryung ;

Schellenberg, Gerard D. ;

Wang, Li-San .

BMC NEUROLOGY, 2010, 10

[10] CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts [J].

Hansson, Oskar ;

Seibyl, John ;

Stomrud, Erik ;

Zetterberg, Henrik ;

Trojanowski, John Q. ;

Bittner, Tobias ;

Lifke, Valeria ;

Corradini, Veronika ;

Eichenlaub, Udo ;

Batrla, Richard ;

Buck, Katharina ;

Zink, Katharina ;

Rabe, Christina ;

Blennow, Kaj ;

Shaw, Leslie M. .

ALZHEIMERS & DEMENTIA, 2018, 14 (11) :1470-1481

← 1 2 3 4 →