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Pathway-Specific Po...
Pathway-Specific Polygenic Risk Scores as Predictors of Amyloid-beta Deposition and Cognitive Function in a Sample at Increased Risk for Alzheimer's Disease
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Darst, B. F. (författare)
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Koscika, R. L. (författare)
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Racine, A. M. (författare)
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Oh, J. M. (författare)
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Krause, R. A. (författare)
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Carlsson, C. M. (författare)
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- Zetterberg, Henrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Blennow, Kaj, 1958 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Christian, B. T. (författare)
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Bendlin, B. B. (författare)
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Okonkwo, O. C. (författare)
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Hogan, K. J. (författare)
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Hermann, B. P. (författare)
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Sager, M. A. (författare)
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Asthana, S. (författare)
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Johnson, S. C. (författare)
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Engelman, C. D. (författare)
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(creator_code:org_t)
- IOS Press, 2017
- 2017
- Engelska.
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 55:2, s. 473-484
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Abstract
Ämnesord
Stäng
- Polygenic risk scores (PRSs) have been used to combine the effects of variants with small effects identified by genome-wide association studies. We explore the potential for using pathway-specific PRSs as predictors of early changes in Alzheimer's disease (AD)-related biomarkers and cognitive function. Participants were from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of adults who were cognitively asymptomatic at enrollment and enriched for a parental history of AD. Using genes associated with AD in the International Genomics of Alzheimer's Project's meta-analysis, we identified clusters of genes that grouped into pathways involved in amyloid-beta (A beta) deposition and neurodegeneration: A beta clearance, cholesterol metabolism, and immune response. Weighted pathway-specific and overall PRSs were developed and compared to APOE alone. Mixed models were used to assess whether each PRS was associated with cognition in 1,200 individuals, cerebral A beta deposition measured using amyloid ligand (Pittsburgh compound B) positron emission imaging in 168 individuals, and cerebrospinal fluid A beta deposition, neurodegeneration, and tau pathology in 111 individuals, with replication performed in an independent sample. We found that PRSs including APOE appeared to be driven by the inclusion of APOE, suggesting that the pathway-specific PRSs used here were not more predictive than an overall PRS or APOE alone. However, pathway-specific PRSs could prove to be useful as more knowledge is gained on the genetic variants involved in specific biological pathways of AD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Alzheimer's disease
- amyloid-beta
- APOE
- cerebrospinal fluid
- cognitive function
- genetic risk scores
- cerebrospinal-fluid biomarkers
- wisconsin-registry
- family-history
- onset
- association
- prevention
- genotypes
- dementia
- children
- people
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Darst, B. F.
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Koscika, R. L.
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Racine, A. M.
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Oh, J. M.
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Krause, R. A.
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Carlsson, C. M.
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visa fler...
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Christian, B. T.
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Bendlin, B. B.
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Okonkwo, O. C.
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Hogan, K. J.
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Hermann, B. P.
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Sager, M. A.
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Asthana, S.
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Johnson, S. C.
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Engelman, C. D.
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visa färre...
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Journal of Alzhe ...
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Göteborgs universitet