Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers
Open accessAbstract
More than 20 genetic loci have been associated with risk for Alzheimer's disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case-control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ 42), tau, and phosphorylated tau (ptau 181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau 181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ 42 near GLIS1 on 1p32.3 (β = -0.059, P = 2.08 × 10-8) and within SERPINB1 on 6p25 (β = -0.025, P = 1.72 × 10-8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10-2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10-2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10-3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ 42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau 181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several novel loci not previously associated with AD risk have been identified through CSF Aβ1-42 and/or tau GWAS, including variants located near the genes GLIS3, GLIS1, GEMC1, and within SERPINB1.
“While the majority of loci overlap with GWAS loci, several novel loci not previously associated with AD risk have also been identified through these analyses, including variants located near the genes GLIS3, GLIS1, GEMC1, and within SERPINB1 [23, 211].”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [211]
In Deming et al., individual GWAS SNPs were not significantly associated with CSF levels of Aβ1-42 or tau.
“Although in their analysis the individual GWAS SNPs were not significantly associated with CSF levels of Aβ1–42 or tau”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [211]
In Deming et al., together the additive risk conferred by all variants was significantly associated with both Aβ1-42 and tau.
“together the additive risk conferred by all variants was significantly associated with both Aβ1–42 and tau.”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [211]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,380 · see citing works
Second-generation PLINK: rising to the challenge of larger and richer datasets
Chang, C. C., Chow, C. C., Tellier, L. C., Vattikuti, S., Purcell, S. M., & Lee, J. J. (2015) · Gigascience · doi:10.1186/s13742-015-0047-8 · Cited by 12,709 · see citing works
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248 · see citing works
GCTA: a tool for genome-wide complex trait analysis
Yang, J., Lee, S. H., Goddard, M. E., & Visscher, P. M. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.11.011 · Cited by 8,279 · see citing works
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164 · see citing works
LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bulik-Sullivan, B. K., Loh, P.-R., Finucane, H. K., Ripke, S., Yang, J., Patterson, N., Daly, M. J., Price, A. L., & Neale, B. M. (2015) · Nature Genetics · doi:10.1038/ng.3211 · Cited by 5,559 · see citing works
METAL: fast and efficient meta-analysis of genomewide association scans
Willer, C. J., Li, Y., & Abecasis, G. R. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq340 · Cited by 5,205 · see citing works
The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
The GTEx Consortium, Ardlie, K. G., Deluca, D. S., Segrè, A. V., Sullivan, T. J., Young, T. R., Gelfand, E. T., Trowbridge, C. A., Maller, J. B., Tukiainen, T., et al. (2015) · Science · doi:10.1126/science.1262110 · Cited by 5,062 · see citing works
Self-citationZhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · see citing works
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336 · see citing works
Self-citationAn atlas of genetic correlations across human diseases and traits
ReproGen Consortium, Bulik-Sullivan, B., Psychiatric Genomics Consortium, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3, Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P.-R., Duncan, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3406 · Cited by 4,255 · see citing works
Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets
Zhu, Z., Zhang, F., Hu, H., Bakshi, A., Robinson, M. R., Powell, J. E., Montgomery, G. W., Goddard, M. E., Wray, N. R., Visscher, P. M., et al. (2016) · Nature Genetics · doi:10.1038/ng.3538 · Cited by 3,352 · see citing works
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
Self-citation<i>TREM2</i> Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
Self-citationAnnotation of functional variation in personal genomes using RegulomeDB
Boyle, A. P., Hong, E. L., Hariharan, M., Cheng, Y., Schaub, M. A., Kasowski, M., Karczewski, K. J., Park, J., Hitz, B. C., Weng, S., et al. (2012) · Genome Research · doi:10.1101/gr.137323.112 · Cited by 2,722 · see citing works
LocusZoom: regional visualization of genome-wide association scan results
Pruim, R. J., Welch, R. P., Sanna, S., Teslovich, T. M., Chines, P. S., Gliedt, T. P., Boehnke, M., Abecasis, G. R., & Willer, C. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq419 · Cited by 2,707 · see citing works
Variant of <i>TREM2</i> Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558 · see citing works
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) · Nature Genetics · doi:10.1038/ng.2711 · Cited by 2,263 · see citing works
Ward, L. D., & Kellis, M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr917 · Cited by 2,229 · see citing works
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134 · see citing works
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Shaw, L. M., Vanderstichele, H., Knapik‐Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., Blennow, K., Soares, H., Simon, A., Lewczuk, P., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21610 · Cited by 2,065 · see citing works
Self-citationOlsson, B., Lautner, R., Andreasson, U., Öhrfelt, A., Portelius, E., Bjerke, M., Hölttä, M., Rosén, C., Olsson, C., Strobel, G., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00070-3 · Cited by 2,049 · see citing works
Self-citationInitiative, T. A. D. N., Hollingworth, P., CHARGE consortium, EADI1 consortium, Harold, D., Sims, R., Gerrish, A., Lambert, J.-C., Carrasquillo, M. M., Abraham, R., et al. (2011) · Nature Genetics · doi:10.1038/ng.803 · Cited by 1,997 · see citing works
Self-citationAnalysis of shared heritability in common disorders of the brain
The Brainstorm Consortium, Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., Duncan, L., Escott-Price, V., Falcone, G. J., Gormley, P., et al. (2018) · Science · doi:10.1126/science.aap8757 · Cited by 1,924 · see citing works
Self-citationNaj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., et al. (2011) · Nature Genetics · doi:10.1038/ng.801 · Cited by 1,901 · see citing works
Self-citationCerebrospinal fluid and plasma biomarkers in Alzheimer disease
Blennow, K., Hampel, H., Weiner, M., & Zetterberg, H. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.4 · Cited by 1,863 · see citing works
Self-citationRole of Genes and Environments for Explaining Alzheimer Disease
Gatz, M., Reynolds, C. A., Fratiglioni, L., Johansson, B., Mortimer, J. A., Berg, S., Fiske, A., & Pedersen, N. L. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.2.168 · Cited by 1,798 · see citing works
Fast and accurate genotype imputation in genome-wide association studies through pre-phasing
Howie, B., Fuchsberger, C., Stephens, M., Marchini, J., & Abecasis, G. R. (2012) · Nature Genetics · doi:10.1038/ng.2354 · Cited by 1,737 · see citing works
Matrix eQTL: ultra fast eQTL analysis via large matrix operations
Shabalin, A. A. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts163 · Cited by 1,694 · see citing works
Systematic identification of trans eQTLs as putative drivers of known disease associations
Westra, H.-J., Peters, M. J., Esko, T., Yaghootkar, H., Schurmann, C., Kettunen, J., Christiansen, M. W., Fairfax, B. P., Schramm, K., Powell, J. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2756 · Cited by 1,658 · see citing works
Skol, A. D., Scott, L. J., Abecasis, G. R., & Boehnke, M. (2006) · Nature Genetics · doi:10.1038/ng1706 · Cited by 1,286 · see citing works
PRSice: Polygenic Risk Score software
Euesden, J., Lewis, C. M., & O’Reilly, P. F. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu848 · Cited by 1,149 · see citing works
qqman: an R package for visualizing GWAS results using Q-Q and manhattan plotsPreprint
Turner, S. (2014) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/005165 · Cited by 1,135 · see citing works
Fagan, A. M., Roe, C. M., Xiong, C., Mintun, M. A., Morris, J. C., & Holtzman, D. M. (2007) · Archives of Neurology · doi:10.1001/archneur.64.3.noc60123 · Cited by 897 · see citing works
Self-citationStaging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores
O’Bryant, S. E. (2008) · Archives of Neurology · doi:10.1001/archneur.65.8.1091 · Cited by 885 · see citing works
Neutrophils promote Alzheimer's disease–like pathology and cognitive decline via LFA-1 integrin
Zenaro, E., Pietronigro, E., Bianca, V. D., Piacentino, G., Marongiu, L., Budui, S., Turano, E., Rossi, B., Angiari, S., Dusi, S., et al. (2015) · Nature Medicine · doi:10.1038/nm.3913 · Cited by 865 · see citing works
Study, T. L. C., Yang, J., Bakshi, A., Zhu, Z., Hemani, G., Vinkhuyzen, A. A. E., Lee, S. H., Robinson, M. R., Perry, J. R. B., Nolte, I. M., et al. (2015) · Nature Genetics · doi:10.1038/ng.3390 · Cited by 745 · see citing works
Sunderland, T., Linker, G., Mirza, N., Putnam, K. T., Friedman, D. L., Kimmel, L. H., Bergeson, J., Manetti, G. J., Zimmermann, M., Tang, B., et al. (2003) · JAMA · doi:10.1001/jama.289.16.2094 · Cited by 656 · see citing works
Morris, J. C., & Price, J. L. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:2:101 · Cited by 513 · see citing works
Self-citationDiagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People
De Meyer, G. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.179 · Cited by 462 · see citing works
Matrix eQTL: Ultra fast eQTL analysis via large matrix operationsPreprint
Shabalin, A. A. (2011) · arXiv (Cornell University) · doi:10.17615/g28n-r219 · Cited by 452 · see citing works
Common polygenic variation enhances risk prediction for Alzheimer’s disease
Escott-Price, V., Sims, R., Bannister, C., Harold, D., Vronskaya, M., Majounie, E., Badarinarayan, N., GERAD/PERADES, consortia, I., Morgan, K., et al. (2015) · Brain · doi:10.1093/brain/awv268 · Cited by 414 · see citing works
Self-citationDelaneau, O., Marchini, J., McVean, G., Donnelly, P., Lunter, G. A., Marchini, J., Myers, S., Hinch, A. G., Iqbal, Z., Mathieson, I., et al. (2014) · Nature Communications · doi:10.1038/ncomms4934 · Cited by 395 · see citing works
GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease
Cruchaga, C., Kauwe, J. S. K., Harari, O., Jin, S. C., Cai, Y., Karch, C. M., Benitez, B. A., Jeng, A. T., Skorupa, T., Carrell, D., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.026 · Cited by 383 · see citing works
Self-citationKanai, M., Matsubara, E., Isoe, K., Urakami, K., Nakashima, K., Arai, H., Sasaki, H., Abe, K., Iwatsubo, T., Kosaka, T., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410440108 · Cited by 340 · see citing works
Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status
Piccio, L., Deming, Y., Del-Águila, J. L., Ghezzi, L., Holtzman, D. M., Fagan, A. M., Fenoglio, C., Galimberti, D., Borroni, B., & Cruchaga, C. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1533-5 · Cited by 337 · see citing works
Self-citationFagan, A. M., Head, D., Shah, A. R., Marcus, D., Mintun, M., Morris, J. C., & Holtzman, D. M. (2009) · Annals of Neurology · doi:10.1002/ana.21559 · Cited by 327 · cited 5× · see citing works
“Low Aβ42 levels (ADRC < 500 pg/mL and ADNI < 192 pg/ mL) have been associated with amyloid positron emission tomography (PET-PIB) evidence of Aβ deposition [25, 69].”
BackgroundResultInfluentialSelf-citationVisscher, P. M., Hemani, G., Vinkhuyzen, A. A. E., Chen, G., Lee, S., Wray, N. R., Goddard, M. E., & Yang, J. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004269 · Cited by 325 · see citing works
HULETTE, C. M., WELSH-BOHMER, K. A., MURRAY, M. G., SAUNDERS, A. M., MASH, D. C., & MCINTYRE, L. M. (1998) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199812000-00009 · Cited by 311 · see citing works
O’Bryant, S. E., Lacritz, L. H., Hall, J. R., Waring, S. C., Chan, W., Khodr, Z. G., Massman, P. J., Hobson, V. L., & Cullum, C. M. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.115 · Cited by 296 · see citing works
Novel genetic loci underlying human intracranial volume identified through genome-wide association
Adams, H., Hibar, D., Chouraki, V., Stein, J., Nyquist, P., Rentería, M. E., Trompet, S., Arias-Vásquez, A., Seshadri, S., Desriviéres, S., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4398 · Cited by 238 · see citing works
Self-citationAssessment of the genetic variance of late-onset Alzheimer's disease
Ridge, P. G., Hoyt, K. B., Boehme, K., Mukherjee, S., Crane, P. K., Haines, J. L., Mayeux, R., Farrer, L. A., Pericak-Vance, M. A., Schellenberg, G. D., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.024 · Cited by 236 · see citing works
Self-citationTrabzuni, D., Ryten, M., Walker, R., Smith, C., Imran, S., Ramasamy, A., Weale, M. E., & Hardy, J. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07432.x · Cited by 229 · cited 1× · see citing works
“p1 portal [33], data from the Brain eQTL Almanac (Braineac) [73] analyzed with the R package MatrixEQTL [68], and the Blood eQTL browser [79] were utilized to Deming et al.”
MethodThe roles of inflammation and immune mechanisms in Alzheimer's disease
Eldik, L. J. V., Carrillo, M. C., Cole, P. E., Feuerbach, D., Greenberg, B., Hendrix, J. A., Kennedy, M. E., Kozauer, N., Margolin, R. A., Molinuevo, J. L., et al. (2016) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2016.05.001 · Cited by 226 · see citing works
MRI and CSF studies in the early diagnosis of Alzheimer's disease
de Leon, M. J., DeSanti, S., Zinkowski, R. P., Mehta, P. D., Praticò, D., Segal, S., Clark, C. M., Kerkman, D. J., DeBernardis, J. F., Li, J., et al. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01381.x · Cited by 221 · see citing works
Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease
Cruchaga, C., Kauwe, J. S. K., Nowotny, P., Bales, K., Pickering, E. H., Mayo, K., Bertelsen, S., Hinrichs, A., Fagan, A. M., Holtzman, D. M., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds296 · Cited by 207 · see citing works
Self-citationKim, S., Swaminathan, S., Shen, L., Risacher, S. L., Nho, K., Foroud, T., Shaw, L. M., Trojanowski, J. Q., Potkin, S. G., Huentelman, M. J., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e318204a397 · Cited by 206 · see citing works
Self-citationPolygenic score prediction captures nearly all common genetic risk for Alzheimer's disease
Escott-Price, V., Shoai, M., Pither, R., Williams, J., & Hardy, J. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.018 · Cited by 183 · see citing works
Migration of neutrophils targeting amyloid plaques in Alzheimer's disease mouse model
Baik, S. H., Cha, M.-Y., Hyun, Y.-M., Cho, H., Hamza, B., Kim, D. K., Han, S.-H., Choi, H., Kim, K. H., Moon, M., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.01.003 · Cited by 181 · see citing works
Sampson, J. N., Wheeler, W. A., Yeager, M., Panagiotou, O. A., Wang, Z., Berndt, S. I., Qing Lan, B., Abnet, C. C., Amundadottir, L. T., Figueroa, J. D., et al. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv279 · Cited by 181 · see citing works
TREM2 is associated with the risk of Alzheimer's disease in Spanish population
Benitez, B. A., Cooper, B., Pastor, P., Jin, S.-C., Lorenzo, E., Cervantes, S., & Cruchaga, C. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.018 · Cited by 163 · see citing works
Self-citationDudbridge, F. (2016) · Genetic Epidemiology · doi:10.1002/gepi.21966 · Cited by 156 · see citing works
Guo, H., Fortune, M. D., Burren, O. S., Schofield, E. C., Todd, J. A., & Wallace, C. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv077 · Cited by 139 · see citing works
Association of APOE with tau-tangle pathology with and without β-amyloid
Farfel, J. M., Yu, L., Jager, P. L. D., Schneider, J. A., & Bennett, D. A. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.09.011 · Cited by 135 · see citing works
Sabuncu, M. R., Buckner, R. L., Smoller, J. W., Lee, P. H., Fischl, B. R., & Sperling, R. A. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr348 · Cited by 130 · see citing works
Cruchaga, C., Kauwe, J. S. K., Mayo, K., Spiegel, N., Bertelsen, S., Nowotny, P., Shah, A. R., Abraham, R., Hollingworth, P., Harold, D., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001101 · Cited by 128 · see citing works
Self-citationFarrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · see citing works
Self-citationLiraz, O., Boehm-Cagan, A., & Michaelson, D. M. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-16 · Cited by 118 · see citing works
GEMC1 is a TopBP1-interacting protein required for chromosomal DNA replication
Balestrini, A., Cosentino, C., Errico, A., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2050 · Cited by 114 · see citing works
Kyrousi, C., Arbi, M., Pilz, G.-A., Pefani, D., Lalioti, M., Ninkovic, J., Götz, M., Lygerou, Z., & Taraviras, S. L. (2015) · Development · doi:10.1242/dev.126342 · Cited by 107 · see citing works
Sleegers, K., Bettens, K., De Roeck, A., Van Cauwenberghe, C., Cuyvers, E., Verheijen, J., Struyfs, H., Van Dongen, J., Vermeulen, S., Engelborghs, S., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.02.013 · Cited by 106 · see citing works
Farley, K., Stolley, J. M., Zhao, P., Cooley, J., & Remold‐O’Donnell, E. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201167 · Cited by 104 · see citing works
Han, M.-R., Schellenberg, G. D., Wang, L.-S., & Initiative, T. A. D. N. (2010) · BMC Neurology · doi:10.1186/1471-2377-10-90 · Cited by 93 · see citing works
Self-citationKauwe, J. S. K., Cruchaga, C., Mayo, K., Fenoglio, C., Bertelsen, S. E., Nowotny, P., Galimberti, D., Scarpini, E. A., Morris, J. C., Fagan, A. M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801227105 · Cited by 89 · see citing works
Self-citationDifferential Binding of Apolipoprotein E Isoforms to Tau and Other Cytoskeletal Proteins
Fleming, L. M., Weisgraber, K. H., Strittmatter, W. J., Troncoso, J. C., & Johnson, G. V. W. (1996) · Experimental Neurology · doi:10.1006/exnr.1996.0064 · Cited by 82 · cited 1× · see citing works
“A few studies have also looked at the role of ApoE in tau pathology [30, 49, 52].”
BackgroundAnalysis of Shared Heritability in Common Disorders of the Brain
(2016) · doi:10.1101/048991 · Cited by 82 · see citing works
Global Analysis of the Impact of Environmental Perturbation on cis-Regulation of Gene Expression
Grundberg, E., Adoue, V., Kwan, T., Ge, B., Duan, Q., Lam, K. C. L., Koka, V., Kindmark, A., Weiss, S. T., Tantisira, K. G., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001279 · Cited by 79 · see citing works
A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin
Deming, Y., Xia, J., Cai, Y., Lord, J., Holmans, P., Bertelsen, S., Holtzman, D., Morris, J. C., Bales, K., Pickering, E. H., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.09.009 · Cited by 66 · see citing works
Self-citationIncreasing CSF phospho-tau levels during cognitive decline and progression to dementia
Andersson, C., Blennow, K., Almkvist, O., Andreasen, N., Engfeldt, P., Johansson, S., Lindau, M. P., & Eriksdotter, M. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.03.027 · Cited by 65 · see citing works
Self-citationLeoni, V., Solomon, A., & Kivipelto, M. (2010) · Biochemical Society Transactions · doi:10.1042/bst0381021 · Cited by 65 · see citing works
Harold, D. H., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng1009-1156d · Cited by 64 · see citing works
Self-citationMartiskainen, H., Helisalmi, S., Viswanathan, J., Kurki, M., Hall, A., Herukka, S., Sarajärvi, T., Natunen, T., Kurkinen, K. M. A., Huovinen, J., et al. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140777 · Cited by 53 · see citing works
Ramirez, A., van der Flier, W. M., Herold, C., Ramonet, D., Heilmann, S., Lewczuk, P., Popp, J., Lacour, A., Drichel, D., Louwersheimer, E., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu372 · Cited by 49 · cited 4× · see citing works
“The associations of the GMNC locus with ptau181 levels and brain volume suggest biological mechanisms other than immune response may be associated with tau-mediated pathology in AD [1, 13, 63].”
BackgroundResultInfluentialSelf-citationKauwe, J. S. K., Cruchaga, C., Bertelsen, S. E., Mayo, K., Latu, W., Nowotny, P., Hinrichs, A. L., Fagan, A. M., Holtzman, D. M., Initiative, A. D. N., et al. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-091711 · Cited by 43 · see citing works
Self-citationLi, Q. S., Parrado, A., Samtani, M. N., Narayan, V. A., & Initiative, A. D. N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134000 · Cited by 39 · see citing works
Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment
Louwersheimer, E., Wolfsgruber, S., Espinosa, A., Lacour, A., Heilmann‐Heimbach, S., Alegret, M., Hernández, I., Rosende‐Roca, M., Tárraga, L., Boada, M., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.01.006 · Cited by 35 · see citing works
Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits
Deming, Y., Xia, J., Cai, Y., Lord, J., Del-Aguila, J. L., Fernandez, M. V., Carrell, D., Black, K., Budde, J., Ma, S., et al. (2016) · Scientific Reports · doi:10.1038/srep18092 · Cited by 28 · see citing works
Self-citationLeprêtre, C., Tchakarska, G., Blibech, H., et al. (2013) · APOPTOSIS · doi:10.1007/s10495-013-0862-2 · Cited by 25 · see citing works
Wu, X., Ye, Y., Kiemeney, L. A. L. M., Sulem, P., Rafnar, Þ., Matullo, G., Seminara, D., Yoshida, T., Saeki, N., Andrew, A. S., et al. (2009) · Nature Genetics · doi:10.1038/ng1009-1156a · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy
Initiative, A. D. N., Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., et al. (2017) · Nature · doi:10.1038/nature24016 · Cited by 1,220 · see citing works
Self-citationMeningeal lymphatics affect microglia responses and anti-Aβ immunotherapy
Da Mesquita, S., Papadopoulos, Z., Dykstra, T., Brase, L., Farias, F. G., Wall, M., Jiang, H., Kodira, C. D., de Lima, K. A., Herz, J., et al. (2021) · Nature · doi:10.1038/s41586-021-03489-0 · Cited by 431 · see citing works
Self-citationThe <i>MS4A</i> gene cluster is a key modulator of soluble TREM2 and Alzheimer’s disease risk
Deming, Y., Filipello, F., Cignarella, F., Cantoni, C., Hsu, S., Mikesell, R., Li, Z., Del-Aguila, J. L., Dube, U., Farias, F. G., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aau2291 · Cited by 271 · see citing works
Self-citationUddin, M. S., Kabir, M. T., Al Mamun, A., Abdel-Daim, M. M., Barreto, G. E., & Ashraf, G. M. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1237-z · Cited by 212 · see citing works
Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis
Roussarie, J.-P., Yao, V., Rodriguez-Rodriguez, P., Oughtred, R., Rust, J., Plautz, Z., Kasturia, S., Albornoz, C., Wang, W., Schmidt, E. F., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.010 · Cited by 180 · see citing works
Causal associations between modifiable risk factors and the Alzheimer's phenome
Andrews, S. J., Fulton‐Howard, B., O'Reilly, P., Marcora, E., Goate, A. M., & collaborators of the Alzheimer's Disease Genetics Consortium (2021) · Annals of Neurology · doi:10.1002/ana.25918 · Cited by 156 · see citing works
Self-citationFang, J., Zhang, P., Wang, Q., Chiang, C.-W., Zhou, Y., Hou, Y., Xu, J., Chen, R., Zhang, B., Lewis, S. J., et al. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00951-z · Cited by 140 · see citing works
Genetic architecture of Alzheimer's disease
Neuner, S. M., TCW, J., & Goate, A. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104976 · Cited by 126 · see citing works
Self-citationSex-specific genetic predictors of Alzheimer’s disease biomarkers
(ADNI), A. D. N. I., Deming, Y., The Alzheimer Disease Genetics Consortium (ADGC), Dumitrescu, L., Barnes, L. L., Thambisetty, M., Kunkle, B., Gifford, K. A., Bush, W. S., Chibnik, L. B., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1881-4 · Cited by 110 · see citing works
Li, Z., Farias, F. H. G., Dube, U., Del-Aguila, J. L., Mihindukulasuriya, K. A., Fernandez, M. V., Ibanez, L., Budde, J. P., Wang, F., Lake, A. M., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-019-02066-0 · Cited by 85 · see citing works
Self-citationLitvinchuk, A., Huynh, T. V., Shi, Y., Jackson, R. J., Finn, M. B., Manis, M., Francis, C. M., Tran, A. C., Sullivan, P. M., Ulrich, J. D., et al. (2021) · Annals of Neurology · doi:10.1002/ana.26043 · Cited by 91 · see citing works
Self-citationInitiative, A. D. N., Tan, M.-S., Yang, Y.-X., Xu, W., Wang, H.-F., Tan, L., Zuo, C.-T., Dong, Q., Tan, L., Suckling, J., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00755-7 · Cited by 71 · see citing works
Self-citationThe genetic regulation of protein expression in cerebrospinal fluid
Hansson, O., Kumar, A., Janelidze, S., Stomrud, E., Insel, P. S., Blennow, K., Zetterberg, H., Fauman, E., Hedman, Å. K., Nagle, M. W., et al. (2023) · EMBO Molecular Medicine · doi:10.15252/emmm.202216359 · Cited by 56 · see citing works
Self-citationSex differences in the genetic architecture of Alzheimer’s disease
Dumitrescu, L., Mayeda, E. R., Sharman, K., Moore, A. M., & Hohman, T. J. (2019) · Current Genetic Medicine Reports · doi:10.1007/s40142-019-0157-1 · Cited by 48 · see citing works
Sullivan, S. E., Liao, M., Smith, R. V., White, C., Lagomarsino, V. N., Xu, J., Taga, M., Bennett, D. A., De Jager, P. L., & Young-Pearse, T. L. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddy376 · Cited by 44 · see citing works
INPP5D modulates TREM2 loss-of-function phenotypes in a β-amyloidosis mouse model
Iguchi, A., Takatori, S., Kimura, S., Muneto, H., Wang, K., Etani, H., Ito, G., Sato, H., Hori, Y., Sasaki, J., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106375 · Cited by 37 · see citing works
Olive, C., Ibanez, L., Farias, F. H. G., Wang, F., Budde, J. P., Norton, J. B., Gentsch, J., Morris, J. C., Li, Z., Dube, U., et al. (2020) · Journal of Alzheimer’s Disease · doi:10.3233/jad-200019 · Cited by 32 · see citing works
Self-citationKloske, C. M., Belloy, M. E., Blue, E. E., Bowman, G. R., Carrillo, M. C., Chen, X., Chiba‐Falek, O., Davis, A. A., Paolo, G. D., Garretti, F., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13877 · Cited by 33 · see citing works
Self-citationKang, M., Ang, T. F. A., Devine, S. A., Sherva, R., Mukherjee, S., Trittschuh, E. H., Gibbons, L. E., Scollard, P., Lee, M., Choi, S.-E., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00633-4 · Cited by 29 · see citing works
Genetic associations with age at dementia onset in the <i>PSEN1 E280A</i> Colombian kindred
Cochran, J. N., Acosta‐Uribe, J., Esposito, B. T., Madrigal, L., Aguillón, D., Giraldo, M. M., Taylor, J. W., Bradley, J., Fulton‐Howard, B., Andrews, S. J., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13021 · Cited by 21 · see citing works
Self-citationRamos de Matos, M., Ferreira, C., Herukka, S.-K., Soininen, H., Janeiro, A., Santana, I., Baldeiras, I., Almeida, M. R., Lleó, A., Dols-Icardo, O., et al. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-180512 · Cited by 18 · see citing works
Li, X., Initiative, O. B. O. A. D. N., Chu, S.-G., Shen, X.-N., Hou, X.-H., Xu, W., Ou, Y.-N., Dong, Q., Tan, L., & Yu, J.-T. (2019) · Aging · doi:10.18632/aging.102435 · Cited by 7 · see citing works
- Authors
- (ADNI), A. D. N. I., Deming, Y., The Alzheimer Disease Genetic Consortium (ADGC), Li, Z., Kapoor, M., Harari, O., Del-Aguila, J. L., Black, K., Carrell, D., Cai, Y., Fernandez, M. V., Budde, J., Ma, S., Saef, B., Howells, B., Huang, K.-L., Bertelsen, S., Fagan, A. M., Holtzman, D. M., Morris, J. C., Kim, S., Saykin, A. J., De Jager, P. L., Albert, M., Moghekar, A., O’Brien, R., Riemenschneider, M., Petersen, R. C., Blennow, K., Zetterberg, H., Minthon, L., Van Deerlin, V. M., Lee, V. M.-Y., Shaw, L. M., Trojanowski, J. Q., Schellenberg, G., Haines, J. L., Mayeux, R., Pericak-Vance, M. A., Farrer, L. A., Peskind, E. R., Li, G., Di Narzo, A. F., Kauwe, J. S. K., Goate, A. M., & Cruchaga, C.
- Affiliations
- Washington University in St. Louis (US)
- State University of New York at Oswego (US)
- Broad Institute (US)
- Johns Hopkins University (US)
- Duke University (US)
- Mayo Clinic (US)
- Sahlgrenska University Hospital (SE)
- Lund University (SE)
- University of Pennsylvania (US)
- Vanderbilt University (US)
- University of Miami (US)
- Boston University (US)
- University of Washington (US)
- Brigham Young University (US)
- Corresponding author
- Cruchaga, Carlos
- ORCID
- Deming, Yuetiva
- Li, Zeran
- Kapoor, Manav
- Harari, Oscar
- Carrell, David
- Budde, John
- Huang, Kuan-lin
- Bertelsen, Sarah
- Fagan, Anne M.
- Holtzman, David M.
- Morris, John C.
- Kim, Sungeun
- Saykin, Andrew J.
- Albert, Marilyn
- Moghekar, Abhay
- O’Brien, Richard
- Petersen, Ronald C.
- Blennow, Kaj
- Zetterberg, Henrik
- Lee, Virginia Man-Yee
- Shaw, Leslie M.
- Trojanowski, John Q.
- Schellenberg, Gerard
- Haines, Jonathan L.
- Mayeux, Richard
- Farrer, Lindsay A.
- Peskind, Elaine R.
- Li, Ge
- Kauwe, John S. K.
- Goate, Alison M.
- Cruchaga, Carlos
- Venue
- Acta Neuropathologica
- Published
- 2017-02-28
- Volume
- 133
- Issue
- 5
- Pages
- 839-856
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC5613285
- OpenAlex
- W2593636852
- Cited by
- 231
- References
- 89
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 26 · 2023: 39 · 2022: 30 · 2021: 28 · 2020: 25 · 2019: 21 · 2018: 23 · 2017: 6
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- PMC
- Funders
- National Institute on Aging (R01AG044546, RF1AG053303, P01AG003991)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, endophenotypes, amyloid-beta 42, phosphorylated tau 181, cerebrospinal fluid biomarkers, disease modifiers, disease progression, age of onset, GLIS1, SERPINB1, clusterin, FERMT2, INPP5D, novel genetic loci, hippocampal gene expression, genetic susceptibility loci
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Genotype, Humans, Middle Aged, Risk Factors, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Genetic Predisposition to Disease, Genome-Wide Association Study, Genetic Loci, Endophenotypes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
