Common polygenic variation enhances risk prediction for Alzheimer’s disease
Open accessAbstract
The identification of subjects at high risk for Alzheimer's disease is important for prognosis and early intervention. We investigated the polygenic architecture of Alzheimer's disease and the accuracy of Alzheimer's disease prediction models, including and excluding the polygenic component in the model. This study used genotype data from the powerful dataset comprising 17 008 cases and 37 154 controls obtained from the International Genomics of Alzheimer's Project (IGAP). Polygenic score analysis tested whether the alleles identified to associate with disease in one sample set were significantly enriched in the cases relative to the controls in an independent sample. The disease prediction accuracy was investigated in a subset of the IGAP data, a sample of 3049 cases and 1554 controls (for whom APOE genotype data were available) by means of sensitivity, specificity, area under the receiver operating characteristic curve (AUC) and positive and negative predictive values. We observed significant evidence for a polygenic component enriched in Alzheimer's disease (P = 4.9 × 10(-26)). This enrichment remained significant after APOE and other genome-wide associated regions were excluded (P = 3.4 × 10(-19)). The best prediction accuracy AUC = 78.2% (95% confidence interval 77-80%) was achieved by a logistic regression model with APOE, the polygenic score, sex and age as predictors. In conclusion, Alzheimer's disease has a significant polygenic component, which has predictive utility for Alzheimer's disease risk and could be a valuable research tool complementing experimental designs, including preventative clinical trials, stem cell selection and high/low risk clinical studies. In modelling a range of sample disease prevalences, we found that polygenic scores almost doubles case prediction from chance with increased prediction at polygenic extremes.
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?
Expanding PRS to include variants below the genome-wide statistical cutoff allows for a more complete view of the genetic contribution to disease risk and seems to provide an improved method for risk prediction over more selective PRS or standard predictors such as APOEε4 alleles, age, and sex.
“risk and seems to provide an improved method for risk prediction over more selective PRS or standard predictors such as APOEε4 alleles, age, and sex [118, 122, 123].”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [122]
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
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821 · 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-citationHowie, B. N., Donnelly, P., & Marchini, J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000529 · Cited by 3,928 · 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-citationAlzheimer disease in the United States (2010–2050) estimated using the 2010 census
Hebert, L. E., Weuve, J., Scherr, P. A., & Evans, D. A. (2013) · Neurology · doi:10.1212/wnl.0b013e31828726f5 · Cited by 2,642 · see citing works
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234 · see citing works
Self-citationThe clinical use of structural MRI in Alzheimer disease
Frisoni, G. B., Fox, N. C., Jack, C. R., Scheltens, P., & Thompson, P. M. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.215 · Cited by 2,113 · see citing works
Initiative, 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-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-citationMaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes
Li, Y., Willer, C. J., Ding, J., Scheet, P., & Abecasis, G. R. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20533 · Cited by 1,843 · see citing works
Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
Escott-Price, V., Bellenguez, C., Wang, L.-S., Choi, S.-H., Harold, D., Jones, L., Holmans, P., Gerrish, A., Vedernikov, A., Richards, A., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094661 · Cited by 1,398 · see citing works
Self-citationA polygenic burden of rare disruptive mutations in schizophrenia
Purcell, S. M., Moran, J. L., Fromer, M., Ruderfer, D., Solovieff, N., Roussos, P., O’Dushlaine, C., Chambert, K., Bergen, S. E., Kähler, A., et al. (2014) · Nature · doi:10.1038/nature12975 · Cited by 1,385 · see citing works
Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease
Seshadri, S. (2010) · JAMA · doi:10.1001/jama.2010.574 · Cited by 1,219 · see citing works
Self-citationLarge-scale genotyping identifies 41 new loci associated with breast cancer risk
Michailidou, K., kConFab Investigators, Australian Ovarian Cancer Study Group, The GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, Hall, P. N., González‐Neira, A., Ghoussaini, M., Dennis, J., Milne, R. L., Schmidt, M. K., et al. (2013) · Nature Genetics · doi:10.1038/ng.2563 · Cited by 1,066 · see citing works
Rare Variants Create Synthetic Genome-Wide Associations
Dickson, S. P., Wang, K., Krantz, I., Hakonarson, H., & Goldstein, D. B. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000294 · Cited by 857 · see citing works
Weiner, M. W., Veitch, D. P., Aisen, P. S., Beckett, L. A., Cairns, N. J., Cedarbaum, J., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.11.001 · Cited by 348 · see citing works
Investigating the Contribution of Common Genetic Variants to the Risk and Pathogenesis of ADHD
Stergiakouli, E., Hamshere, M., Holmans, P., Langley, K., Zaharieva, I., Hawi, Z., Kent, L., Gill, M., Williams, N., Owen, M., et al. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11040551 · Cited by 220 · see citing works
Self-citationLee, S. H., Harold, D., Nyholt, D. R., ANZGene Consortium, International Endogene Consortium, the Genetic and Environmental Risk for Alzheimer's disease (GERAD1) Consortium, Goddard, M. E., Zondervan, K. T., Williams, J., Montgomery, G. W., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/dds491 · Cited by 217 · see citing works
Self-citationConvergent genetic and expression data implicate immunity in Alzheimer's disease
International Genomics of Alzheimer's Disease Consortium (IGAP), Jones, L., Lambert, J., Wang, L., Choi, S., Harold, D., Vedernikov, A., Escott‐Price, V., Stone, T., Richards, A., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.05.1757 · Cited by 199 · see citing works
Self-citationGenetic risk profiles for depression and anxiety in adult and elderly cohorts
Demirkan, A., Penninx, B. W. J. H., Hek, K., Wray, N. R., Amin, N., Aulchenko, Y. S., van Dyck, R., de Geus, E. J. C., Hofman, A., Uitterlinden, A. G., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.65 · Cited by 175 · see citing works
Polygenic risk of P arkinson disease is correlated with disease age at onset
Escott‐Price, V., Nalls, M. A., Morris, H. R., Lubbe, S. J., Brice, A., Gasser, T., Heutink, P., Wood, N. W., Hardy, J., Singleton, A., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24335 · Cited by 135 · see citing works
Self-citationPolygenic Risk for Schizophrenia Is Associated with Cognitive Change Between Childhood and Old Age
McIntosh, A. M., Gow, A. J., Michelle Luciano, A., Davies, G., Liewald, D. C. M., Harris, S. E., Corley, J., Hall, J., Starr, J. M., Porteous, D. J., et al. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.01.011 · Cited by 122 · see citing works
Modeling the prevalence and incidence of Alzheimer’s disease and mild cognitive impairment
Yesavage, J. A., O'Hara, R. M., KRAEMER, H. C., Noda, A. M., Taylor, J. L., Ferris, S. H., Gély-Nargeot, M.-C., Rosen, A. C., Friedman, L., Sheikh, J. I., et al. (2002) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(02)00020-1 · Cited by 109 · see citing works
Moskvina, V. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.448 · Cited by 60 · see citing works
Evidence for a polygenic contribution to androgenetic alopecia
Heilmann‐Heimbach, S., Brockschmidt, F. F., Hillmer, A. M., Hanneken, S., Eigelshoven, S., Ludwig, K. U., Herold, C., Mangold, E., Becker, T., Kruse, R., et al. (2013) · British Journal of Dermatology · doi:10.1111/bjd.12443 · Cited by 44 · see citing works
Chapman, J., Rees, E., Harold, D. H., Ivanov, D. K., Gerrish, A., Sims, R., Hollingworth, P., Stretton, A., Holmans, P., Owen, M. J., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds476 · Cited by 32 · see citing works
Self-citationNo evidence that extended tracts of homozygosity are associated with Alzheimer's disease
Sims, R., Dwyer, S., Harold, D. H., Gerrish, A., Hollingworth, P., Chapman, J., Jones, N., Abraham, R., Ivanov, D. K., Pahwa, J. S., et al. (2011) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31216 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
1 of the 29 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32205-4 · Cited by 5,465 · see citing works
Lane, C. A., Hardy, J., & Schott, J. M. (2018) · European Journal of Neurology · doi:10.1111/ene.13439 · Cited by 2,616 · see citing works
Self-citationARUK Consortium, Sims, R., GERAD/PERADES, C., van der Lee, S. J., Naj, A. C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B. W., Boland, A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3916 · Cited by 1,126 · see citing works
Self-citationThe genetic architecture of Parkinson's disease
Blauwendraat, C., Nalls, M. A., & Singleton, A. B. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30287-x · Cited by 1,114 · see citing works
Association of Lifestyle and Genetic Risk With Incidence of Dementia
Lourida, I., Hannon, E., Littlejohns, T. J., Langa, K. M., Hyppönen, E., Kuzma, E., & Llewellyn, D. J. (2019) · JAMA · doi:10.1001/jama.2019.9879 · Cited by 881 · see citing works
López, J. A., González, H. M., & Léger, G. C. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-12-804766-8.00013-3 · Cited by 834 · see citing works
Towards clinical utility of polygenic risk scores
Lambert, S. A., Abraham, G., & Inouye, M. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz187 · Cited by 566 · see citing works
A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward
Belloy, M. E., Napolioni, V., & Greicius, M. D. (2019) · Neuron · doi:10.1016/j.neuron.2019.01.056 · Cited by 570 · see citing works
The multiplex model of the genetics of Alzheimer's disease
Sims, R., Hill, M., & Williams, J. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0599-5 · Cited by 466 · see citing works
Self-citationDesikan, R. S., Fan, C. C., Wang, Y., Schork, A. J., Cabral, H. J., Cupples, L. A., Thompson, W. K., Besser, L., Kukull, W. A., Holland, D., et al. (2017) · PLoS Medicine · doi:10.1371/journal.pmed.1002258 · Cited by 395 · see citing works
Self-citationThe WPA-Lancet psychiatry commission on the future of psychiatry
Bhugra, D., Tasman, A., Pathare, S., Priebe, S., Smith, S., Torous, J., Arbuckle, M. R., Langford, A., Alarcón, R. D., Chiu, H. F. K., et al. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(17)30333-4 · Cited by 392 · see citing works
Lewczuk, P., Riederer, P. F., O’Bryant, S. E., Verbeek, M. M., Dubois, B., Visser, P. J., Jellinger, K. A., Engelborghs, S., Ramı́rez, A., Parnetti, L., et al. (2017) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2017.1375556 · Cited by 308 · see citing works
van der Lee, S. J., Wolters, F. J., Ikram, M. K., Albert Hofman, D., Ikram, M. A., Amin, N., & van Duijn, C. M. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30053-x · Cited by 297 · see citing works
Novel Alzheimer risk genes determine the microglia response to amyloid-β but not to TAU pathology
Sierksma, A., Lu, A., Mancuso, R., Fattorelli, N., Thrupp, N., Salta, E., Zoco, J., Blum, D., Buée, L., De Strooper, B., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.201910606 · Cited by 291 · see citing works
Gene discovery in amyotrophic lateral sclerosis: implications for clinical management
Al-Chalabi, A., van den Berg, L. H., & Veldink, J. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.182 · Cited by 287 · see citing works
Bis, J. C., Jian, X., Kunkle, B. W., Chen, Y., Hamilton-Nelson, K. L., Bush, W. S., Salerno, W. J., Lancour, D., Ma, Y., Renton, A. E., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-018-0112-7 · Cited by 248 · see citing works
Self-citationRisk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture
Zhang, Q., Sidorenko, J., Couvy-Duchesne, B., Marioni, R. E., Wright, M. J., Goate, A. M., Marcora, E., Huang, K.-L., Porter, T., Laws, S. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18534-1 · Cited by 272 · see citing works
Self-citation(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., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1685-y · Cited by 231 · see citing works
Self-citationIdentifying individuals with high risk of Alzheimer’s disease using polygenic risk scores
Leonenko, G., Baker, E. A., Stevenson‐Hoare, J. O., Sierksma, A. S. R., Fiers, M. W. E. J., Williams, J. H., Strooper, B. D., & Escott‐Price, V. (2021) · Nature Communications · doi:10.1038/s41467-021-24082-z · Cited by 226 · see citing works
Self-citationGenetics of Alzheimer’s disease: where we are, and where we are going
Bellenguez, C., Grenier-Boley, B., & Lambert, J.-C. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.11.024 · Cited by 215 · see citing works
Self-citationGene–environment interactions in Alzheimer disease: the emerging role of epigenetics
Migliore, L., & Coppedè, F. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00714-w · Cited by 217 · see citing works
Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer’s Disease Genetics
Podleśny-Drabiniok, A., Marcora, E., & Goate, A. M. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.002 · Cited by 211 · see citing works
Self-citationMachine Learning SNP Based Prediction for Precision Medicine
Ho, D., Schierding, W. S., Wake, M. A., Saffery, R., & O'Sullivan, J. M. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00267 · Cited by 211 · see citing works
Lee, C., Bendriem, R. M., Wu, W. W., & Shen, R. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0362-8 · Cited by 198 · see citing works
Models for predicting risk of dementia: a systematic review
Hou, X., Feng, L., Zhang, C. M., Cao, X., Tan, L., & Yu, J. (2018) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2018-318212 · Cited by 191 · see citing works
Polygenic risk score analysis of pathologically confirmed Alzheimer disease
Escott‐Price, V., Myers, A., Huentelman, M. J., & Hardy, J. (2017) · Annals of Neurology · doi:10.1002/ana.24999 · Cited by 178 · see citing works
Self-citationPolygenic risk of Alzheimer disease is associated with early- and late-life processes
Mormino, E. C., Sperling, R. A., Holmes, A. J., Buckner, R. L., Jager, P. L. D., Smoller, J. W., Sabuncu, M. R., Initiative, A. D. N., Initiative, A. D. N., Weiner, M. W., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000002922 · Cited by 170 · see citing works
A multiomics approach to heterogeneity in Alzheimer’s disease: focused review and roadmap
Badhwar, A., McFall, G. P., Sapkota, S., Black, S. E., Chertkow, H. M., Duchesne, S., Masellis, M., Li, L., Dixon, R. A., & Bellec, P. (2019) · Brain · doi:10.1093/brain/awz384 · Cited by 168 · see citing works
Koelewijn, L., Lancaster, T. M., Linden, D. E. J., Dima, D. C., Routley, B. C., Magazzini, L., Barawi, K., Brindley, L. M., Adams, R., Tansey, K. E., et al. (2019) · eLife · doi:10.7554/elife.36011 · Cited by 145 · see citing works
Translating genetic risk of Alzheimer’s disease into mechanistic insight and drug targets
Sierksma, A. S. R., Escott‐Price, V., & Strooper, B. D. (2020) · Science · doi:10.1126/science.abb8575 · Cited by 149 · see citing works
Self-citationPolygenic Scores to Assess Atherosclerotic Cardiovascular Disease Risk
Aragam, K. G., & Natarajan, P. (2020) · Circulation Research · doi:10.1161/circresaha.120.315928 · Cited by 146 · see citing works
Dissecting the clinical heterogeneity of early-onset Alzheimer’s disease
Sirkis, D. W., Bonham, L. W., Johnson, T. P., La Joie, R., & Yokoyama, J. S. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01531-9 · Cited by 151 · see citing works
Protective genes and pathways in Alzheimer’s disease: moving towards precision interventions
Seto, M., Weiner, R. L., Dumitrescu, L., & Hohman, T. J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00452-5 · Cited by 135 · see citing works
Genome-wide association studies for Alzheimer’s disease: bigger is not always better
Escott-Price, V., & Hardy, J. (2022) · Brain Communications · doi:10.1093/braincomms/fcac125 · Cited by 119 · see citing works
Self-citationThe genetic landscape of Alzheimer disease
Carmona, S., Hardy, J., & Guerreiro, R. J. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64076-5.00026-0 · Cited by 133 · see citing works
Self-citationArtificial intelligence for biomarker discovery in Alzheimer's disease and dementia
Winchester, L. M., Harshfield, E. L., Shi, L., Badhwar, A., Khleifat, A. A., Clarke, N., Dehsarvi, A., Lengyel, I., Lourida, I., Madan, C. R., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13390 · Cited by 130 · see citing works
Polygenic 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
Self-citationCruchaga, C., Del‐Aguila, J. L., Saef, B., Black, K., Fernandez, M. V., Budde, J., Ibanez, L., Deming, Y., Kapoor, M., Tosto, G., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.08.013 · Cited by 138 · see citing works
Self-citationGenetic 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-citationDHA/EPA (Omega-3) and LA/GLA (Omega-6) as Bioactive Molecules in Neurodegenerative Diseases
Kousparou, C. A., Fyrilla, M., Stephanou, A., & Patrikios, I. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310717 · Cited by 123 · see citing works
PRECISION MEDICINE - THE GOLDEN GATE FOR DETECTION, TREATMENT AND PREVENTION OF ALZHEIMER’S DISEASE
Hampel, H. J., O’Bryant, S. E., Castrillo, J. I., Ritchie, C. W., Rojkova, K., Broich, K., Benda, N., Nisticò, R., Frank, R., Dubois, B., et al. (2016) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2016.112 · Cited by 116 · see citing works
Self-citationClinical application of next-generation sequencing to the practice of neurology
Rexach, J. E., Lee, H.-N., Martinez-Agosto, J., Nemeth, A., & Fogel, B. (2019) · Lancet Neurology · doi:10.1016/s1474-4422(19)30033-x · Cited by 101 · see citing works
Genetic risk for alzheimer disease is distinct from genetic risk for amyloid deposition
Leonenko, G., Shoai, M., Bellou, E., Sims, R., Williams, J., Hardy, J., Escott‐Price, V., & Initiative, T. A. D. N. (2019) · Annals of Neurology · doi:10.1002/ana.25530 · Cited by 114 · see citing works
Self-citationLogue, M. W., Panizzon, M. S., Elman, J. A., Gillespie, N. A., Hatton, S. N., Gustavson, D. E., Andreassen, O. A., Dale, A. M., Franz, C. E., Lyons, M. J., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0030-8 · Cited by 113 · see citing works
Ranson, J. M., Rittman, T., Hayat, S. A., Brayne, C., Jessen, F., Blennow, K., van Duijn, C. M., Barkhof, F., Tang, E. Y. H., Mummery, C. J., et al. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00895-4 · Cited by 113 · see citing works
Self-citationComplement-Mediated Events in Alzheimer’s Disease: Mechanisms and Potential Therapeutic Targets
Tenner, A. J. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901068 · Cited by 99 · see citing works
Lane, C., Parker, T. D., Cash, D. M., Macpherson, K., Donnachie, E., Murray‐Smith, H., Barnes, A., Barker, S., Beasley, D. G., Brás, J., et al. (2017) · BMC Neurology · doi:10.1186/s12883-017-0846-x · Cited by 100 · see citing works
Self-citationFoley, S. F., Tansey, K. E., Caseras, X., Lancaster, T. M., Bracht, T., Parker, G. D., Hall, J., Williams, J. H., & Linden, D. E. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.02.033 · Cited by 95 · see citing works
Self-citationBiomarkers of dementia in obstructive sleep apnea
Baril, A., Carrier, J., Lafrenière, A., Warby, S. C., Poirier, J., Osorio, R. S., Ayas, N., Dubé, M., Petit, D., & Gosselin, N. (2018) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2018.08.001 · Cited by 96 · see citing works
Stocker, H. R., Möllers, T., Perna, L., & Brenner, H. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0221-8 · Cited by 96 · see citing works
Houck, A. L., Seddighi, S., & Driver, J. A. (2018) · Current Aging Science · doi:10.2174/1874609811666180223154436 · Cited by 95 · see citing works
Polygenic risk and hazard scores for Alzheimer's disease prediction
Leonenko, G., Sims, R., Shoai, M., Frizzati, A., Bossù, P., Spalletta, G., Fox, N. C., Williams, J. H., Hardy, J., & Escott‐Price, V. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.716 · Cited by 95 · see citing works
Self-citationMeasuring heritable contributions to Alzheimer’s disease: polygenic risk score analysis with twins
Karlsson, I., Escott‐Price, V., Gatz, M., Hardy, J., Pedersen, N. L., Shoai, M., & Reynolds, C. A. (2021) · Brain Communications · doi:10.1093/braincomms/fcab308 · Cited by 94 · see citing works
Self-citationStep by step: towards a better understanding of the genetic architecture of Alzheimer’s disease
Lambert, J.-C., Ramirez, A., Grenier-Boley, B., & Bellenguez, C. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02076-1 · Cited by 87 · see citing works
Self-citationSmith, A. R., Smith, R. G., Condliffe, D., Hannon, E. J., Schalkwyk, L. C., Mill, J. S., & Lunnon, K. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.008 · Cited by 89 · see citing works
Dissociable influences of APOE ε4 and polygenic risk of AD dementia on amyloid and cognition
Ge, T., Sabuncu, M. R., Smoller, J. W., Sperling, R. A., Mormino, E. C., & Initiative, A. D. N. (2018) · Neurology · doi:10.1212/wnl.0000000000005415 · Cited by 90 · see citing works
Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease
Allen, G. I., Amoroso, N., Anghel, C. V., Balagurusamy, V. S. K., Bare, J. C., Beaton, D., Bellotti, R., Bennett, D. A., Boehme, K. L., Boutros, P. C., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.02.006 · Cited by 85 · see citing works
Alzheimer’s disease polygenic risk score as a predictor of conversion from mild-cognitive impairment
Chaudhury, S. R., Brookes, K. J., Patel, T., Fallows, A., Guetta‐Baranes, T., Turton, J. C., Guerreiro, R. J., Brás, J., Hardy, J., Francis, P. T., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0485-7 · Cited by 89 · see citing works
Self-citationPolygenic hazard score, amyloid deposition and Alzheimer’s neurodegeneration
Tan, C. H., Bonham, L. W., Fan, C. C., Mormino, E. C., Sugrue, L. P., Broce, I., Hess, C. P., Yokoyama, J. S., Rabinovici, G. D., Miller, B. L., et al. (2018) · Brain · doi:10.1093/brain/awy327 · Cited by 87 · see citing works
Self-citationIbáñez, L., Dube, U., Saef, B. A., Budde, J., Black, K., Medvedeva, A., Del‐Aguila, J. L., Davis, A. A., Perlmutter, J. S., Harari, O., et al. (2017) · BMC Neurology · doi:10.1186/s12883-017-0978-z · Cited by 83 · see citing works
Self-citationElovainio, M., Lahti, J., Pirinen, M., Pulkki-Råback, L., Malmberg, A., Lipsanen, J., Virtanen, M., Kivimäki, M., & Hakulinen, C. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-053936 · Cited by 85 · see citing works
Alzheimer’s Disease: Pathogenesis and Therapeutic Interventions
Ogbodo, J. O., Agbo, C. P., Njoku, U. O., Ogugofor, M. O., Egba, S. I., Ihim, S. A., Echezona, A. C., Brendan, K. C., Upaganlawar, A. B., & Upasani, C. D. (2021) · Current Aging Science · doi:10.2174/1874609814666210302085232 · Cited by 81 · see citing works
Role of environmental pollutants in Alzheimer’s disease: a review
Mir, R. H., Sawhney, G., Pottoo, F. H., Mohi-ud-din, R., Madishetti, S., Jachak, S. M., Ahmed, Z., & Masoodi, M. H. (2020) · Environmental Science and Pollution Research · doi:10.1007/s11356-020-09964-x · Cited by 78 · see citing works
Classifying Alzheimer's disease with brain imaging and genetic data using a neural network framework
Ning, K., Chen, B., Sun, F., Hobel, Z. B., Zhao, L., Matloff, W. J., & Toga, A. W. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.04.009 · Cited by 76 · see citing works
The Role of Genetics in Advancing Precision Medicine for Alzheimer’s Disease—A Narrative Review
Freudenberg‐Hua, Y., Li, W., & Davies, P. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00108 · Cited by 74 · see citing works
Genetic study of multimodal imaging Alzheimer’s disease progression score implicates novel loci
Scelsi, M. A., Khan, R. R., Lorenzi, M., Christopher, L., Greicius, M. D., Schott, J. M., Ourselin, S., & Altmann, A. (2018) · Brain · doi:10.1093/brain/awy141 · Cited by 73 · see citing works
Genomics and Functional Genomics of Alzheimer's Disease
Kamboh, M. I. (2022) · Neurotherapeutics · doi:10.1007/s13311-021-01152-0 · Cited by 73 · see citing works
Clinical utility of polygenic risk scores: a critical 2023 appraisal
Koch, S., Schmidtke, J., Krawczak, M., & Caliebe, A. (2023) · Journal of Community Genetics · doi:10.1007/s12687-023-00645-z · Cited by 73 · see citing works
Polygenic Risk Scores in Alzheimer's Disease: Current Applications and Future Directions
(2020) · doi:10.3389/fdgth.2020.00014 · Cited by 71 · see citing works
Self-citationAxelrud, L. K., Santoro, M. L., Pine, D. S., Talarico, F., Gadelha, A., Manfro, G. G., Pan, P. M., Jackowski, A. P., Picon, F. A., Brietzke, E. M., et al. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17050529 · Cited by 71 · see citing works
Sex-dependent autosomal effects on clinical progression of Alzheimer’s disease
Fan, C. C., Banks, S. J., Thompson, W. K., Chen, C., McEvoy, L. K., Tan, C. H., Kukull, W. A., Bennett, D. A. A., Farrer, L. A., Mayeux, R. P., et al. (2020) · Brain · doi:10.1093/brain/awaa164 · Cited by 69 · see citing works
Self-citationStocker, H. R., Perna, L., Weigl, K., Möllers, T., Schöttker, B., Thomsen, H., Holleczek, B., Rujescu, D., & Brenner, H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0764-y · Cited by 68 · see citing works
Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study
Jia, L., Li, F., Wei, C., Zhu, M., Qu, Q., Qin, W., Tang, Y., Shen, L., Wang, Y., Shen, L., et al. (2021) · Brain · doi:10.1093/brain/awaa364 · Cited by 67 · see citing works
Creese, B., Arathimos, R., Brooker, H. J., Aarsland, D., Corbett, A., Lewis, C. M., Ballard, C. G., & Ismail, Z. (2021) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12164 · Cited by 68 · see citing works
Alzheimer’s disease: where next for anti-amyloid therapies?
Hardy, J., & Strooper, B. D. (2017) · Brain · doi:10.1093/brain/awx059 · Cited by 66 · see citing works
Self-citationCardiovascular health, genetic risk, and risk of dementia in the Framingham Heart Study
Peloso, G. M., Beiser, A., Satizábal, C. L., Xanthakis, V., Vasan, R. S., Pase, M. P., DeStefano, A. L., & Seshadri, S. S. (2020) · Neurology · doi:10.1212/wnl.0000000000010306 · Cited by 67 · see citing works
Self-citationGenetics of Alzheimer's Disease
Kim, J. H. (2018) · Dementia and Neurocognitive Disorders · doi:10.12779/dnd.2018.17.4.131 · Cited by 67 · see citing works
Altmann, A., Scelsi, M. A., Shoai, M., de Silva, E., Aksman, L. M., Cash, D. M., Hardy, J., Schott, J. M., & Initiative, A. D. N. (2020) · Brain Communications · doi:10.1093/braincomms/fcz047 · Cited by 65 · see citing works
Self-citationPolygenic risk scores in familial Alzheimer disease
Tosto, G., Bird, T. D., Tsuang, D. W., Bennett, D., Boeve, B. F., Cruchaga, C., Faber, K. M., Foroud, T., Farlow, M. R., Goate, A., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000003734 · Cited by 62 · see citing works
Self-citationProgress in Polygenic Composite Scores in Alzheimer’s and Other Complex Diseases
Chasioti, D., Yan, J., Nho, K. T., & Saykin, A. J. (2019) · Trends in Genetics · doi:10.1016/j.tig.2019.02.005 · Cited by 59 · see citing works
From Polygenic Scores to Precision Medicine in Alzheimer’s Disease: A Systematic Review
Harrison, J. R., Mistry, S., Muskett, N., & Escott‐Price, V. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191233 · Cited by 61 · see citing works
Self-citationThe Correlation between Inflammatory Biomarkers and Polygenic Risk Score in Alzheimer’s Disease
Morgan, A. R., Touchard, S., O’Hagan, C., Sims, R., Majounie, E., Escott‐Price, V., Jones, L., Williams, J. H., & Morgan, B. P. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160889 · Cited by 59 · see citing works
Self-citationGenetic testing in dementia — utility and clinical strategies
Koriath, C., Kenny, J., Ryan, N. S., Rohrer, J. D., Schott, J. M., Houlden, H., Fox, N. C., Tabrizi, S. J., & Mead, S. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-00416-1 · Cited by 59 · see citing works
Self-citationPorter, T., Burnham, S. C., Milicic, L., Savage, G. R., Maruff, P. T., Lim, Y. Y., Li, Q.-X., Ames, D. J., Masters, C. L., Rainey‐Smith, S. R., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180713 · Cited by 56 · see citing works
Initiative*, T. A. D. N., Zettergren, A., Lord, J., Ashton, N. J., Benedet, A. L., Karikari, T. K., Lantero‐Rodriguez, J., Snellman, A., Suárez‐Calvet, M., Proitsi, P., et al. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00754-8 · Cited by 57 · see citing works
Genetics of Alzheimer’s Disease: the Importance of Polygenic and Epistatic Components
Raghavan, N. S., & Tosto, G. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0787-1 · Cited by 55 · see citing works
Matthews, P. M., & Sudlow, C. L. M. (2015) · Brain · doi:10.1093/brain/awv335 · Cited by 56 · see citing works
Is bigger always better? The importance of cortical configuration with respect to cognitive ability
Vuoksimaa, E., Panizzon, M. S., Chen, C., Fiecas, M. J. A., Eyler, L. T., Fennema‐Notestine, C., Hagler, D. J., Franz, C. E., Jak, A. J., Lyons, M. J., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.01.049 · Cited by 54 · see citing works
Richards, M., James, S., Sizer, A., Sharma, N., Rawle, M. J., Davis, D. H. J., & Kuh, D. J. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-024404 · Cited by 54 · see citing works
Genetic risk for Alzheimer disease predicts hippocampal volume through the human lifespan
Walhovd, K. B., Fjell, A. M., Sørensen, Ø., Mowinckel, A. M., Reinbold, C. S., Idland, A., Watne, L. O., Franke, A., Dobričić, V., Kilpert, F., et al. (2020) · Neurology Genetics · doi:10.1212/nxg.0000000000000506 · Cited by 53 · see citing works
Drange, O. K., Smeland, O. B., Shadrin, A. A., Finseth, P. I., Witoelar, A., & Frei, O. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00220 · Cited by 53 · see citing works
Age-dependent effect of APOE and polygenic component on Alzheimer's disease
Bellou, E., Baker, E. A., Leonenko, G., Bracher‐Smith, M., Daunt, P., Menzies, G. E., Williams, J. H., & Escott‐Price, V. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.04.024 · Cited by 50 · see citing works
Self-citationKremen, W. S., Panizzon, M. S., Elman, J. A., Granholm, E. L., Andreassen, O. A., Dale, A. M., Gillespie, N. A., Gustavson, D. E., Logue, M. W., Lyons, M. J., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.09.001 · Cited by 50 · see citing works
Modifiable cardiovascular risk factors and genetics for targeted prevention of dementia
Rasmussen, I. J., & Frikke‐Schmidt, R. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad293 · Cited by 54 · see citing works
Polygenic Risk Score Analysis of Alzheimer's Disease in Cases without APOE4 or APOE2 Alleles
Escott‐Price, V., Myers, A., Huentelman, M. J., Shoai, M., & Hardy, J. (2019) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2018.46 · Cited by 52 · see citing works
Self-citationFrom Common to Rare Variants: The Genetic Component of Alzheimer Disease
Nicolas, G., Charbonnier, C., & Campion, D. (2016) · Human Heredity · doi:10.1159/000452256 · Cited by 47 · see citing works
Lupton, M. K., Robinson, G. A., Adam, R. J., Rose, S., Byrne, G. J., Salvado, O., Pachana, N. A., Almeida, O. P., McAloney, K., Gordon, S. D., et al. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102527 · Cited by 47 · see citing works
Understanding the contributions of VPS35 and the retromer in neurodegenerative disease
Williams, E. T., Chen, X., Otero, P. A., & Moore, D. J. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105768 · Cited by 49 · see citing works
Polygenic risk and pleiotropy in neurodegenerative diseases
Bellou, E., Stevenson-Hoare, J. O., & Escott-Price, V. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104953 · Cited by 48 · see citing works
Self-citationWhat does heritability of Alzheimer’s disease represent?
Baker, E. A., Leonenko, G., Schmidt, K. M., Hill, M., Myers, A., Shoai, M., de Rojas, I., Tesi, N., Holstege, H. H., van der Flier, W. M., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0281440 · Cited by 49 · see citing works
Self-citation
- Authors
- Escott-Price, V., Sims, R., Bannister, C., Harold, D., Vronskaya, M., Majounie, E., Badarinarayan, N., GERAD/PERADES, consortia, I., Morgan, K., Passmore, P., Holmes, C., Powell, J., Brayne, C., Gill, M., Mead, S., Goate, A., Cruchaga, C., Lambert, J.-C., van Duijn, C., Maier, W., Ramirez, A., Holmans, P., Jones, L., Hardy, J., Seshadri, S., Schellenberg, G. D., Amouyel, P., & Williams, J.
- Affiliations
- Cardiff University (GB)
- Trinity College Dublin (IE)
- University of Nottingham (GB)
- Queen's University Belfast (GB)
- University of Cambridge (GB)
- King's College London (GB)
- Washington University in St. Louis (US)
- Inserm (FR)
- University of Bonn (DE)
- UCL Queen Square Institute of Neurology (GB)
- Boston University (US)
- ORCID
- Sims, Rebecca
- Bannister, Christian
- Harold, Denise
- Badarinarayan, Nandini
- Morgan, Kevin
- Passmore, Peter
- Holmes, Clive
- Powell, John
- Brayne, Carol
- Gill, Michael
- Mead, Simon
- Goate, Alison
- Cruchaga, Carlos
- Lambert, Jean-Charles
- Holmans, Peter
- Jones, Lesley
- Hardy, John
- Seshadri, Sudha
- Schellenberg, Gerard D.
- Amouyel, Philippe
- Williams, Julie
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-10-21
- Volume
- 138
- Issue
- 12
- Pages
- 3673-3684
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC5006219
- OpenAlex
- W2193207784
- Cited by
- 414
- References
- 29
- Citations by year
- 2026: 20 · 2025: 34 · 2024: 29 · 2023: 52 · 2022: 45 · 2021: 51 · 2020: 51 · 2019: 52 · 2018: 31 · 2017: 31 · 2016: 16 · 2015: 2
- FWCI
- 19.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Nottingham ePrints (University of Nottingham) (submittedVersion, cc-by)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Repository@Nottingham (University of Nottingham) (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- DZNE Pub (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- National Institute for Social Care and Health Research
- Health and Care Research Wales
- EU Joint Programme – Neurodegenerative Disease Research
- Alzheimer's Society
- National Institute for Health and Care Research (NF-SI-0611-10084)
- Cardiff University
- Dementias Platform UK
- Medical Research Council (MR/L023784/2, MR/L023784/1, MR/L501517/1, MR/K013041/1, MR/L501529/1, MR/L010305/1, MR/M009076/1)
- National Institute on Aging (U01AG049505, P30AG010124, U01AG032984, R01AG033193, R01AG008122, U24AG021886)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, polygenic risk score, polygenic architecture, risk prediction, apolipoprotein E, genome-wide association study, prediction accuracy
- MeSH terms
- Alleles, Alzheimer Disease, Apolipoproteins E, Genetic Testing, Genotype, Humans, Risk, ROC Curve, Genetic Variation, Logistic Models, Case-Control Studies, Genetic Predisposition to Disease, Multifactorial Inheritance, Genome-Wide Association Study
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
