PMID- 25570489
OWN - NLM
STAT- MEDLINE
DCOM- 20151030
LR  - 20230218
IS  - 2694-0604 (Electronic)
IS  - 2375-7477 (Linking)
VI  - 2014
DP  - 2014
TI  - Effects of genetic variation on the dynamics of neurodegeneration in Alzheimer's 
      disease.
PG  - 2464-7
LID - 10.1109/EMBC.2014.6944121 [doi]
AB  - Although many genetic markers are identified as being associated with Alzheimer's 
      disease (AD), not much is known about their association with the structural 
      changes that happen as the disease progresses. In this study, we investigate the 
      genetic etiology of neurodegeneration in AD by associating genetic markers with 
      atrophy profiles obtained using patient data from the Alzheimer's Disease 
      Neuroimaging Initiative (ADNI) cohort. The atrophy profiles were quantified using 
      a linear least-squares regression model over the span of patient enrollment, and 
      used as imaging features throughout the analysis. A subset of the imaging 
      features were selected for genetic association based on their ability to 
      discriminate between healthy individuals and AD patients in a Support Vector 
      Machines (SVM) classifier. Each imaging feature was associated with 
      single-nucleotide polymorphisms (SNPs) using a linear model that included age and 
      cognitive impairment scores as covariates to correct for normal disease 
      progression. After false discovery rate correction, we observed 53 significant 
      associations between SNPs and our imaging features, including associations of 
      ventricular enlargement with SNPs on estrogen receptor 1 (ESR1) and 
      sortilin-related VPS10 domain containing receptor 1 (SORCS1), hippocampal atrophy 
      with SNPs on ESR1, and cerebral atrophy with SNPs on transferrin (TF) and amyloid 
      beta precursor protein (APP). This study provides important insights into genetic 
      predictors of specific types of neurodegeneration that could potentially be used 
      to improve the efficacy of treatment strategies for the disease and allow the 
      development of personalized treatment plans based on each patient's unique 
      genetic profile.
FAU - Printy, Blake P
AU  - Printy BP
FAU - Verma, Nishant
AU  - Verma N
FAU - Cowperthwaite, Matthew C
AU  - Cowperthwaite MC
FAU - Markey, Mia K
AU  - Markey MK
CN  - Alzheimer's Disease Neuroimaging Initiative
LA  - eng
GR  - U24 AG021886/AG/NIA NIH HHS/United States
GR  - U01 AG024904/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Annu Int Conf IEEE Eng Med Biol Soc
JT  - Annual International Conference of the IEEE Engineering in Medicine and Biology 
      Society. IEEE Engineering in Medicine and Biology Society. Annual International 
      Conference
JID - 101763872
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Alzheimer Disease/diagnosis/*genetics/pathology/physiopathology
MH  - Atrophy/pathology
MH  - Cognition
MH  - Cohort Studies
MH  - Disease Progression
MH  - Genetic Markers/genetics
MH  - Hippocampus/metabolism/pathology
MH  - Humans
MH  - Least-Squares Analysis
MH  - Neuroimaging
MH  - *Polymorphism, Single Nucleotide
MH  - Support Vector Machine
EDAT- 2015/01/09 06:00
MHDA- 2015/10/31 06:00
CRDT- 2015/01/09 06:00
PHST- 2015/01/09 06:00 [entrez]
PHST- 2015/01/09 06:00 [pubmed]
PHST- 2015/10/31 06:00 [medline]
AID - 10.1109/EMBC.2014.6944121 [doi]
PST - ppublish
SO  - Annu Int Conf IEEE Eng Med Biol Soc. 2014;2014:2464-7. doi: 
      10.1109/EMBC.2014.6944121.