PMID- 27662287
OWN - NLM
STAT- MEDLINE
DCOM- 20180222
LR  - 20190430
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 55
IP  - 2
DP  - 2017
TI  - Pathway-Specific Polygenic Risk Scores as Predictors of Amyloid-beta Deposition
      and Cognitive Function in a Sample at Increased Risk for Alzheimer's Disease.
PG  - 473-484
AB  - 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 (Abeta) deposition and
      neurodegeneration: Abeta 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 Abeta deposition measured using amyloid 
      ligand (Pittsburgh compound B) positron emission imaging in 168 individuals, and 
      cerebrospinal fluid Abeta 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.
FAU - Darst, Burcu F
AU  - Darst BF
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Department of Population Health Sciences, University of Wisconsin School of
      Medicine and Public Health, Madison, WI, USA.
FAU - Koscik, Rebecca L
AU  - Koscik RL
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
FAU - Racine, Annie M
AU  - Racine AM
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Alzheimer's Diseases Research Center, University of Wisconsin School of Medicine 
      and Public Health, Madison, WI, USA.
FAU - Oh, Jennifer M
AU  - Oh JM
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Alzheimer's Diseases Research Center, University of Wisconsin School of Medicine 
      and Public Health, Madison, WI, USA.
FAU - Krause, Rachel A
AU  - Krause RA
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Alzheimer's Diseases Research Center, University of Wisconsin School of Medicine 
      and Public Health, Madison, WI, USA.
FAU - Carlsson, Cynthia M
AU  - Carlsson CM
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
AD  - Alzheimer's Diseases Research Center, University of Wisconsin School of Medicine 
      and Public Health, Madison, WI, USA.
AD  - Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial VA
      Hospital, Madison, WI, USA.
FAU - Zetterberg, Henrik
AU  - Zetterberg H
AD  - Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, 
      Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the
      University of Gothenburg, Sweden.
AD  - Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square,
      London, UK.
FAU - Blennow, Kaj
AU  - Blennow K
AD  - Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, 
      Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the
      University of Gothenburg, Sweden.
FAU - Christian, Bradley T
AU  - Christian BT
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Department of Medical Physics, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
FAU - Bendlin, Barbara B
AU  - Bendlin BB
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
AD  - Alzheimer's Diseases Research Center, University of Wisconsin School of Medicine 
      and Public Health, Madison, WI, USA.
FAU - Okonkwo, Ozioma C
AU  - Okonkwo OC
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
AD  - Alzheimer's Diseases Research Center, University of Wisconsin School of Medicine 
      and Public Health, Madison, WI, USA.
AD  - Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial VA
      Hospital, Madison, WI, USA.
FAU - Hogan, Kirk J
AU  - Hogan KJ
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
AD  - Department of Anesthesiology, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
FAU - Hermann, Bruce P
AU  - Hermann BP
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
AD  - Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial VA
      Hospital, Madison, WI, USA.
AD  - Department of Neurology, University of Wisconsin School of Medicine and Public
      Health, WI, USA.
FAU - Sager, Mark A
AU  - Sager MA
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
FAU - Asthana, Sanjay
AU  - Asthana S
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
AD  - Alzheimer's Diseases Research Center, University of Wisconsin School of Medicine 
      and Public Health, Madison, WI, USA.
AD  - Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial VA
      Hospital, Madison, WI, USA.
FAU - Johnson, Sterling C
AU  - Johnson SC
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
AD  - Alzheimer's Diseases Research Center, University of Wisconsin School of Medicine 
      and Public Health, Madison, WI, USA.
AD  - Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial VA
      Hospital, Madison, WI, USA.
FAU - Engelman, Corinne D
AU  - Engelman CD
AD  - University of Wisconsin, Madison, WI, USA.
AD  - Department of Population Health Sciences, University of Wisconsin School of
      Medicine and Public Health, Madison, WI, USA.
AD  - Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and
      Public Health, Madison, WI, USA.
AD  - Alzheimer's Diseases Research Center, University of Wisconsin School of Medicine 
      and Public Health, Madison, WI, USA.
LA  - eng
GR  - R01 AG037639/AG/NIA NIH HHS/United States
GR  - UL1 TR000427/TR/NCATS NIH HHS/United States
GR  - T15 LM007359/LM/NLM NIH HHS/United States
GR  - R01 AG027161/AG/NIA NIH HHS/United States
GR  - P30 AG017266/AG/NIA NIH HHS/United States
GR  - R01 AG021155/AG/NIA NIH HHS/United States
GR  - T32 AG000213/AG/NIA NIH HHS/United States
GR  - P2C HD047873/HD/NICHD NIH HHS/United States
GR  - P50 AG033514/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Aniline Compounds)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Thiazoles)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alzheimer Disease/cerebrospinal fluid/*complications/diagnostic imaging/*genetics
MH  - Amyloid beta-Peptides/*cerebrospinal fluid
MH  - Aniline Compounds/metabolism
MH  - Apolipoproteins E/genetics
MH  - Cognition Disorders/diagnostic imaging/*etiology
MH  - Female
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Humans
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Neuropsychological Tests
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Positron-Emission Tomography
MH  - Risk Factors
MH  - Thiazoles/metabolism
MH  - tau Proteins/cerebrospinal fluid
PMC - PMC5123972
MID - NIHMS824971
OTO - NOTNLM
OT  - *APOE
OT  - *Alzheimer's disease
OT  - *Pittsburgh compound B
OT  - *WRAP
OT  - *amyloid-beta
OT  - *cerebrospinal fluid
OT  - *cognitive function
OT  - *genetic risk scores
OT  - *genetics
OT  - *polygenic risk scores
EDAT- 2016/09/24 06:00
MHDA- 2018/02/23 06:00
CRDT- 2016/09/24 06:00
PHST- 2016/09/24 06:00 [pubmed]
PHST- 2018/02/23 06:00 [medline]
PHST- 2016/09/24 06:00 [entrez]
AID - JAD160195 [pii]
AID - 10.3233/JAD-160195 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2017;55(2):473-484. doi: 10.3233/JAD-160195.