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Genetic risk score predicting accelerated progression from mild cognitive impairment to Alzheimer’s disease
Ist Teil von
Journal of Neural Transmission, 2013-05, Vol.120 (5), p.807-812
Ort / Verlag
Vienna: Springer Vienna
Erscheinungsjahr
2013
Quelle
MEDLINE
Beschreibungen/Notizen
Aside from
APOE
, the genetic factors that influence the progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) remain largely unknown. We assessed whether a genetic risk score (GRS), based on eight non-
APOE
genetic variants previously associated with AD risk in genome-wide association studies, is associated with either risk of conversion or with rapid progression from MCI to AD. Among 288 subjects with MCI, follow-up (mean 26.3 months) identified 118 MCI-converters to AD and 170 MCI-nonconverters. We genotyped
ABCA7
rs3764650,
BIN1
rs744373,
CD2AP
rs9296559,
CLU
rs1113600,
CR1
rs1408077,
MS4A4E
rs670139,
MS4A6A
rs610932, and
PICALM
rs3851179. For each subject we calculated a cumulative GRS, defined as the number of risk alleles (range 0–16) with each allele weighted by the AD risk odds ratio. GRS was not associated with risk of conversion from MCI to AD. However, MCI-converters to AD harboring six or more risk alleles (second and third GRS tertiles) progressed twofold more rapidly to AD when compared with those with less than six risk alleles (first GRS tertile). Our GRS is a first step toward development of prediction models for conversion from MCI to AD that incorporate aggregate genetic factors.