Sorl1 as an Alzheimer's disease predisposition gene?
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressively disabling impairments in memory, cognition, and non-cognitive behavioural symptoms. Sporadic AD is multifactorial and genetically complex. While several monogenic mutations cause early-onset AD and gene alleles have been suggested as AD susceptibility factors, the only extensively validated susceptibility gene for late-onset AD is the apolipoprotein E (APOE) epsilon4 allele. Alleles of the APOE gene do not account for all of the genetic load calculated to be responsible for AD predisposition. Recently, polymorphisms across the neuronal sortilin-related receptor (SORL1) gene were shown to be significantly associated with AD in several cohorts. Here we present the results of our large case-control whole-genome scan at over 500,000 polymorphisms which presents weak evidence for association and potentially narrows the association interval.
Webster
Jennifer A
JA
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Ariz., USA.
Myers
Amanda J
AJ
Pearson
John V
JV
Craig
David W
DW
Hu-Lince
Diane
D
Coon
Keith D
KD
Zismann
Victoria L
VL
Beach
Thomas
T
Leung
Doris
D
Bryden
Leslie
L
Halperin
Rebecca F
RF
Marlowe
Lauren
L
Kaleem
Mona
M
Huentelman
Matthew J
MJ
Joshipura
Keta
K
Walker
Douglas
D
Heward
Christopher B
CB
Ravid
Rivka
R
Rogers
Joseph
J
Papassotiropoulos
Andreas
A
Hardy
John
J
Reiman
Eric M
EM
Stephan
Dietrich A
DA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics
D005819:Genetic Markers; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human