Common variants at 12q14 and 12q24 are associated with hippocampal volume.
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2012Citation:
Bis JC, DeCarli C, Smith AV, van der Lijn F, Crivello F, Fornage M, Debette S, Shulman JM, Schmidt H, Srikanth V, Schuur M, Yu L, Choi SH, Sigurdsson S, Verhaaren BF, DeStefano AL, Lambert JC, Jack CR, Struchalin M, Stankovich J, Ibrahim-Verbaas CA, Fleischman D, Zijdenbos A, den Heijer T, Mazoyer B, Coker LH, Enzinger C, Danoy P, Amin N, Arfanakis K, van Buchem MA, de Bruijn RF, Beiser A, Dufouil C, Huang J, Cavalieri M, Thomson R, Niessen WJ, Chibnik LB, Gislason GK, Hofman A, Pikula A, Amouyel P, Freeman KB, Phan TG, Oostra BA, Stein JL, Medland SE, Vasquez AA, Hibar DP, Wright MJ, Franke B, Martin NG, Thompson PM, Nalls MA, Uitterlinden AG, Au R, Elbaz A, Beare RJ, van Swieten JC, Lopez OL, Harris TB, Chouraki V, Breteler MM, De Jager PL, Becker JT, Vernooij MW, Knopman D, Fazekas F, Wolf PA, van der Lugt A, Gudnason V, Longstreth WT, Brown MA, Bennett DA, van Duijn CM, Mosley TH, Schmidt R, Tzourio C, Launer LJ, Ikram MA, Seshadri S, Common variants at 12q14 and 12q24 are associated with hippocampal volume., Nature genetics, 44, 5, 2012, 545-551Download Item:
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Abstract:
Aging is associated with reductions in hippocampal volume (HV) that are accelerated by
Alzheimer?s disease and vascular risk factors. Our genome-wide association study of dementia-
free persons (n=9,232) identified 46 SNPs at four loci with p-values <4.0?10
-7
. Two additional
samples (n=2,318) replicated associations at 12q24 within
MSRB3/WIF1
(discovery + replication,
rs17178006; p=5.3?10
-11
) and at 12q14 near
HRK/FBXW8
(rs7294919; p=2.9?10
-11
). Remaining
associations included one 2q24 SNP within
DPP4
(rs6741949; p=2.9?10
-7
) and nine 9p33 SNPs
within
ASTN2
(rs7852872; p=1.0?10
-7
) that were also associated with HV (p<0.05) in a third
younger, more heterogeneous sample (n=7,794). The
ASTN2
SNP was also associated with
decline in cognition in a largely independent sample (n=1,563). These associations implicate
genes related to apoptosis (
HRK
), development (
WIF1)
, oxidative stress (
MSR3B
), ubiquitination
(
FBXW8
), enzymes targeted by new diabetes medications (
DPP4
), and neuronal migration
(ASTN2), indicating novel genetic influences that influence hippocampal size and possibly the
risk of cognitive decline and dementia
Author's Homepage:
http://people.tcd.ie/acorvinhttp://people.tcd.ie/donoghug
Description:
PUBLISHED
Author: DONOHOE, GARY (JAMES); CORVIN, AIDEN PETER
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Series/Report no:
Nature genetics;44;
5;
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novel genetic influencesLicences: