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

Richard Sherva, Yorghos Tripodis, David A. Bennett, Lori B. Chibnik, Paul K. Crane, Philip L. De Jager, Lindsay A. Farrer, Andrew Saykin, Joshua M. Shulman, Adam Naj, Robert C. Green

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalAlzheimer's and Dementia
Volume10
Issue number1
DOIs
StatePublished - Jan 2014

Fingerprint

Genome-Wide Association Study
Alzheimer Disease
Single Nucleotide Polymorphism
Genes
Amyloid Precursor Protein Secretases
Cognitive Dysfunction
Amyloid beta-Protein Precursor
Neuroimaging
Cognition
Linear Models
Alleles
Genome

Keywords

  • Alzheimer's disease
  • Cognitive decline
  • GWAS

ASJC Scopus subject areas

  • Health Policy
  • Epidemiology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Sherva, R., Tripodis, Y., Bennett, D. A., Chibnik, L. B., Crane, P. K., De Jager, P. L., ... Green, R. C. (2014). Genome-wide association study of the rate of cognitive decline in Alzheimer's disease. Alzheimer's and Dementia, 10(1), 45-52. https://doi.org/10.1016/j.jalz.2013.01.008

Genome-wide association study of the rate of cognitive decline in Alzheimer's disease. / Sherva, Richard; Tripodis, Yorghos; Bennett, David A.; Chibnik, Lori B.; Crane, Paul K.; De Jager, Philip L.; Farrer, Lindsay A.; Saykin, Andrew; Shulman, Joshua M.; Naj, Adam; Green, Robert C.

In: Alzheimer's and Dementia, Vol. 10, No. 1, 01.2014, p. 45-52.

Research output: Contribution to journalArticle

Sherva, R, Tripodis, Y, Bennett, DA, Chibnik, LB, Crane, PK, De Jager, PL, Farrer, LA, Saykin, A, Shulman, JM, Naj, A & Green, RC 2014, 'Genome-wide association study of the rate of cognitive decline in Alzheimer's disease', Alzheimer's and Dementia, vol. 10, no. 1, pp. 45-52. https://doi.org/10.1016/j.jalz.2013.01.008
Sherva R, Tripodis Y, Bennett DA, Chibnik LB, Crane PK, De Jager PL et al. Genome-wide association study of the rate of cognitive decline in Alzheimer's disease. Alzheimer's and Dementia. 2014 Jan;10(1):45-52. https://doi.org/10.1016/j.jalz.2013.01.008
Sherva, Richard ; Tripodis, Yorghos ; Bennett, David A. ; Chibnik, Lori B. ; Crane, Paul K. ; De Jager, Philip L. ; Farrer, Lindsay A. ; Saykin, Andrew ; Shulman, Joshua M. ; Naj, Adam ; Green, Robert C. / Genome-wide association study of the rate of cognitive decline in Alzheimer's disease. In: Alzheimer's and Dementia. 2014 ; Vol. 10, No. 1. pp. 45-52.
@article{661c76ab1e8040c69b284e3c7f6e1466,
title = "Genome-wide association study of the rate of cognitive decline in Alzheimer's disease",
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.",
keywords = "Alzheimer's disease, Cognitive decline, GWAS",
author = "Richard Sherva and Yorghos Tripodis and Bennett, {David A.} and Chibnik, {Lori B.} and Crane, {Paul K.} and {De Jager}, {Philip L.} and Farrer, {Lindsay A.} and Andrew Saykin and Shulman, {Joshua M.} and Adam Naj and Green, {Robert C.}",
year = "2014",
month = "1",
doi = "10.1016/j.jalz.2013.01.008",
language = "English",
volume = "10",
pages = "45--52",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Genome-wide association study of the rate of cognitive decline in Alzheimer's disease

AU - Sherva, Richard

AU - Tripodis, Yorghos

AU - Bennett, David A.

AU - Chibnik, Lori B.

AU - Crane, Paul K.

AU - De Jager, Philip L.

AU - Farrer, Lindsay A.

AU - Saykin, Andrew

AU - Shulman, Joshua M.

AU - Naj, Adam

AU - Green, Robert C.

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Cognitive decline

KW - GWAS

UR - http://www.scopus.com/inward/record.url?scp=84891146110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891146110&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2013.01.008

DO - 10.1016/j.jalz.2013.01.008

M3 - Article

C2 - 23535033

AN - SCOPUS:84891146110

VL - 10

SP - 45

EP - 52

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

IS - 1

ER -