Cited by 196Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsGenetic Associations and Epidemiology

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Genome-wide association study of the rate of cognitive decline in Alzheimer’s disease

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Sherva, Richard, Tripodis, Yorghos, Bennett, David A., Chibnik, Lori B., Crane, Paul K., de Jager, Philip L., Farrer, Lindsay A., Saykin, Andrew J., Shulman, Joshua M., Naj, Adam, Green, Robert C., The GENAROAD Consortium, The Alzheimer's Disease Neuroimaging Initiative, and The Alzheimer's Disease Genetics Consortium·2014·Alzheimer's & Dementia

DOI 10.1016/j.jalz.2013.01.008PMC PMC3760995

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Abstract

Background: Substantial interindividual variability exists in the disease trajectories of Alzheimer's disease (AD) patients. Some decline rapidly whereas others decline slowly, and there are no known explanations for this variability. We describe the first genome‐wide association study to examine rate of cognitive decline in a sample of AD patients with longitudinal measures of cognition. Methods: The discovery sample was 303 AD cases recruited in the Alzheimer's Disease Neuroimaging Initiative and the replication sample was 323 AD cases from the Religious Orders Study and Rush Memory and Aging Project. In the discovery sample, Alzheimer's Disease Assessment Scale–cognitive subscale responses were tested for association with genome‐wide single‐nucleotide polymorphism (SNP) data using linear regression. We tested the 65 most significant SNPs from the discovery sample for association in the replication sample. Results: We identified SNPs in the spondin 1 gene ( SPON1 ), the minor alleles of which were significantly associated with a slower rate of decline (rs11023139, P = 7.0 × 10 −11 ) in the discovery sample. A SPON1 SNP 5.5 kb upstream was associated with decline in the replication sample (rs11606345, P = .002). Conclusion: SPON1 has not been previously associated with AD risk, but is plausibly related because the gene product binds to the amyloid precursor protein and inhibits its cleavage by β‐secretase. These data suggest that SPON1 may be associated with the differential rate of cognitive decline in AD.

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Additional file 5 of Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations
Liu, H., Barnes, J., Pedrosa, E., Herman, N. S., Salas, F., Wang, P., Zheng, D., & Lachman, H. M. (2020) · Figshare · doi:10.6084/m9.figshare.12285422
Additional file 1 of Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations
Liu, H., Barnes, J., Pedrosa, E., Herman, N. S., Salas, F., Wang, P., Zheng, D., & Lachman, H. M. (2020) · Figshare · doi:10.6084/m9.figshare.12285389
Additional file 7 of Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations
Liu, H., Barnes, J., Pedrosa, E., Herman, N. S., Salas, F., Wang, P., Zheng, D., & Lachman, H. M. (2020) · Figshare · doi:10.6084/m9.figshare.12285440
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Additional file 3 of Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations
Liu, H., Barnes, J., Pedrosa, E., Herman, N. S., Salas, F., Wang, P., Zheng, D., & Lachman, H. M. (2020) · Figshare · doi:10.6084/m9.figshare.12285410
Additional file 2 of Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations
Liu, H., Barnes, J., Pedrosa, E., Herman, N. S., Salas, F., Wang, P., Zheng, D., & Lachman, H. M. (2020) · Figshare · doi:10.6084/m9.figshare.12285398
Additional file 11 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596664
Additional file 14 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596673
Additional file 3 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596640
Additional file 4 of Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations
Liu, H., Barnes, J., Pedrosa, E., Herman, N. S., Salas, F., Wang, P., Zheng, D., & Lachman, H. M. (2020) · Figshare · doi:10.6084/m9.figshare.12285416
Additional file 2 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596637
Additional file 8 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596655
Additional file 1 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596634
Additional file 17 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596682
Additional file 6 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596649
Additional file 6 of Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations
Liu, H., Barnes, J., Pedrosa, E., Herman, N. S., Salas, F., Wang, P., Zheng, D., & Lachman, H. M. (2020) · Figshare · doi:10.6084/m9.figshare.12285431
Additional file 4 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596643
Additional file 5 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596646
Additional file 16 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596679
Additional file 10 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596661
Additional file 15 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596676
Additional file 9 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596658
Additional file 7 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596652
Additional file 13 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596670
Additional file 12 of Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations
Wang, J., Wu, J., Sun, Q., Wu, Q., Li, Y., Duan, S., Yang, L., Wu, W., Wang, Z., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26596667
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Authors: Sherva, R., Tripodis, Y., Bennett, D. A., Chibnik, L. B., Crane, P. K., de Jager, P. L., Farrer, L. A., Saykin, A. J., Shulman, J. M., Naj, A., Green, R. C., & The GENAROAD Consortium, T. A. D. N. I.
Affiliations: Boston University (US)
Department of Medicine (Biomedical Genetics) Boston University School of Medicine Boston MA USA
Corresponding author: Sherva, Richard
ORCID: Sherva, Richard
Tripodis, Yorghos
Bennett, David A.
Chibnik, Lori B.
Crane, Paul K.
Farrer, Lindsay A.
Saykin, Andrew J.
Shulman, Joshua M.
Naj, Adam
Green, Robert C.
Venue: Alzheimer's & Dementia
Publisher: Wiley
Published: 2013-03-26
Volume: 10
Issue: 1
Pages: 45-52
ISSN: 1552-5260 (ISSN-L)
1552-5279
DOI: 10.1016/j.jalz.2013.01.008
PMC: PMC3760995
OpenAlex: W2034937783
Cited by: 180
References: 34
Citations by year: 2026: 4 · 2025: 6 · 2024: 23 · 2023: 18 · 2022: 15 · 2021: 15 · 2020: 18 · 2019: 12 · 2018: 14 · 2017: 15 · 2016: 11 · 2015: 11 · 2014: 14 · 2013: 3
FWCI: 9.21
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Alzheimer s & Dementia (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (U01 AG024904)
National Institute on Aging
National Institute of Biomedical Imaging and Bioengineering
Dana Foundation (HG02213, AG027841)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: Alzheimer's disease
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Female, Follow-Up Studies, Genotype, Humans, Male, Neuropsychological Tests, Phenotype, Extracellular Matrix Proteins, Polymorphism, Single Nucleotide, Apolipoprotein E4, Genome-Wide Association Study

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