PMID- 28222519
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20181113
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 57
IP  - 1
DP  - 2017
TI  - Genetic Stratification to Identify Risk Groups for Alzheimer's Disease.
PG  - 275-283
LID - 10.3233/JAD-161070 [doi]
AB  - Stratification by genetic risk factors for Alzheimer's disease (AD) may help
      identify groups with the greatest disease risk. Biological changes that cause
      late-onset AD are likely to occur years, if not decades prior to diagnosis. Here,
      we select a subset of the Generation Scotland: Scottish Family Health Study
      cohort in a likely preclinical age-range of 60-70 years (subset n = 3,495 with
      cognitive and genetic data). We test for cognitive differences by polygenic risk 
      scores for AD. The polygenic scores are constructed using all available SNPs,
      excluding those within a 500 kb distance of the APOE locus. Additive and
      multiplicative effects of APOE status on these associations are investigated.
      Small memory decrements were observed in those with high polygenic risk scores
      for AD (standardized beta -0.04, p = 0.020). These associations were independent 
      of APOE status. There was no difference in AD polygenic scores across APOE
      haplotypes (p = 0.72). Individuals with high compared to low polygenic risk
      scores for AD (top and bottom 5% of the distribution) show cognitive decrements, 
      albeit much smaller than for APOE varepsilon4varepsilon4 compared to
      varepsilon3varepsilon3 individuals (2.3 versus 3.5 fewer points on the processing
      speed test, and 1.8 versus 2.8 fewer points on the memory test). Polygenic risk
      scores for AD may help identify older individuals at greatest risk of cognitive
      decline and preclinical AD.
FAU - Marioni, Riccardo E
AU  - Marioni RE
AD  - Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 
      Edinburgh, UK.
AD  - Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute
      of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
AD  - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 
      Australia.
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, QLD,
      Australia.
FAU - Campbell, Archie
AU  - Campbell A
AD  - Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute
      of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
FAU - Hagenaars, Saskia P
AU  - Hagenaars SP
AD  - Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 
      Edinburgh, UK.
AD  - Department of Psychology, University of Edinburgh, Edinburgh, UK.
AD  - Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
FAU - Nagy, Reka
AU  - Nagy R
AD  - Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular
      Medicine, University of Edinburgh, Edinburgh, UK.
FAU - Amador, Carmen
AU  - Amador C
AD  - Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular
      Medicine, University of Edinburgh, Edinburgh, UK.
FAU - Hayward, Caroline
AU  - Hayward C
AD  - Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular
      Medicine, University of Edinburgh, Edinburgh, UK.
FAU - Porteous, David J
AU  - Porteous DJ
AD  - Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 
      Edinburgh, UK.
AD  - Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute
      of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
FAU - Visscher, Peter M
AU  - Visscher PM
AD  - Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 
      Edinburgh, UK.
AD  - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 
      Australia.
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, QLD,
      Australia.
FAU - Deary, Ian J
AU  - Deary IJ
AD  - Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 
      Edinburgh, UK.
AD  - Department of Psychology, University of Edinburgh, Edinburgh, UK.
LA  - eng
GR  - BB/F019394/1/Biotechnology and Biological Sciences Research Council/United
      Kingdom
GR  - CZD/16/6/4/Chief Scientist Office/United Kingdom
GR  - MR/K026992/1/Medical Research Council/United Kingdom
GR  - 104036/Z/14/Z/Wellcome Trust/United Kingdom
GR  - MR/K026992/1/Medical Research Council/United Kingdom
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
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 (Apolipoproteins E)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*classification/*genetics
MH  - Apolipoproteins E/genetics
MH  - Cognitive Dysfunction/classification/genetics
MH  - Cohort Studies
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Middle Aged
MH  - *Multifactorial Inheritance
MH  - Neuropsychological Tests
MH  - Polymorphism, Single Nucleotide
MH  - Scotland
MH  - Self Report
PMC - PMC5345653
OTO - NOTNLM
OT  - *Alzheimer's disease
OT  - *apolipoprotein E
OT  - *cognitive function
OT  - *genetics
OT  - *polygenic traits
EDAT- 2017/02/23 06:00
MHDA- 2018/02/27 06:00
CRDT- 2017/02/23 06:00
PHST- 2017/02/23 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2017/02/23 06:00 [entrez]
AID - JAD161070 [pii]
AID - 10.3233/JAD-161070 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2017;57(1):275-283. doi: 10.3233/JAD-161070.