TY - JOUR
T1 - Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease
AU - Alzheimer’s Disease Neuroimaging Initiative (ADNI)
AU - Horgusluoglu-Moloch, Emrin
AU - Nho, Kwangsik
AU - Risacher, Shannon L.
AU - Kim, Sungeun
AU - Foroud, Tatiana
AU - Shaw, Leslie M.
AU - Trojanowski, John Q.
AU - Aisen, Paul S.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Lovestone, Simon
AU - Simmons, Andrew
AU - Weiner, Michael W.
AU - Saykin, Andrew J.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/12
Y1 - 2017/12
N2 - Alzheimer's disease (AD) patients display hippocampal atrophy, memory impairment, and cognitive decline. New neurons are generated throughout adulthood in 2 regions of the brain implicated in AD, the dentate gyrus of the hippocampus and the subventricular zone of the olfactory bulb. Disruption of this process contributes to neurodegenerative diseases including AD, and many of the molecular players in AD are also modulators of adult neurogenesis. However, the genetic mechanisms underlying adult neurogenesis in AD have been underexplored. To address this gap, we performed a gene-based association analysis in cognitively normal and impaired participants using neurogenesis pathway-related candidate genes curated from existing databases, literature mining, and large-scale genome-wide association study findings. A gene-based association analysis identified adenosine A2a receptor (ADORA2A) as significantly associated with hippocampal volume and the association between rs9608282 within ADORA2A and hippocampal volume was replicated in the meta-analysis after multiple comparison adjustments (p = 7.88 × 10−6). The minor allele of rs9608282 in ADORA2A is associated with larger hippocampal volumes and better memory.
AB - Alzheimer's disease (AD) patients display hippocampal atrophy, memory impairment, and cognitive decline. New neurons are generated throughout adulthood in 2 regions of the brain implicated in AD, the dentate gyrus of the hippocampus and the subventricular zone of the olfactory bulb. Disruption of this process contributes to neurodegenerative diseases including AD, and many of the molecular players in AD are also modulators of adult neurogenesis. However, the genetic mechanisms underlying adult neurogenesis in AD have been underexplored. To address this gap, we performed a gene-based association analysis in cognitively normal and impaired participants using neurogenesis pathway-related candidate genes curated from existing databases, literature mining, and large-scale genome-wide association study findings. A gene-based association analysis identified adenosine A2a receptor (ADORA2A) as significantly associated with hippocampal volume and the association between rs9608282 within ADORA2A and hippocampal volume was replicated in the meta-analysis after multiple comparison adjustments (p = 7.88 × 10−6). The minor allele of rs9608282 in ADORA2A is associated with larger hippocampal volumes and better memory.
KW - ADORA2A
KW - Alzheimer's disease
KW - Gene-based association analysis
KW - Hippocampal volume
KW - Memory
KW - NMDA-receptor antagonist
KW - Neurogenesis
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UR - http://www.scopus.com/inward/citedby.url?scp=85029479296&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2017.08.010
DO - 10.1016/j.neurobiolaging.2017.08.010
M3 - Article
C2 - 28941407
AN - SCOPUS:85029479296
SN - 0197-4580
VL - 60
SP - 92
EP - 103
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -