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Common variants at 12q14 and 12q24 are associated with hippocampal volume

Citation

Bis, JC and Decarli, C and Smith, AV and Van Der Lijn, F and Crivello, F and Fornage, M and Debette, S and Shulman, JM and Schmidt, H and Srikanth, V and Schuur, M and Yu, L and Choi, S-H and Sigurdsson, S and Verhaaren, BFJ and Destefano, AL and Lambert, J-C and Jack, CR and Struchalin, M and Stankovich, J and Ibrahim-Verbaas, CA and Fleischman, D and Zijdenbos, A and Den Heijer, T and Mazoyer, B and Coker, LH and Enzinger, C and Danoy, P and Amin, N and Arfanakis, K and Van Buchem, MA and De Bruijn, RFAG and Beiser, A and Dufouil, C and Huang, J and Cavalieri, M and Thomson, R and Niessen, WJ and Chibnik, LB and Gislason, GK and Hofman, A and Pikula, A and Amouyel, P and Freeman, KB and Phan, TG and Oostra, BA and Stein, JL and Medland, SE and Vasquez, AA and Hibar, DP and Wright, MJ and Franke, B and Martin, NG and Thompson, PM and Nalls, MA and Uitterlinden, AG and Au, R and Elbaz, A and Beare, RJ and Van Swieten, JC and Lopez, OL and Harris, TB and Chouraki, V and Breteler, MMB and De Jager, PL and Becker, JT and Vernooij, MW and Knopman, D and Fazekas, F and Wolf, PA and Van Der Lugt, A and Gudnason, V and Longstreth, WT and Brown, MA and Bennett, DA and Van Duijn, CM and Mosley, TH and Schmidt, R and Tzourio, C and Launer, LJ and Ikram, MA and Seshadri, S, Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium, Common variants at 12q14 and 12q24 are associated with hippocampal volume, Nature Genetics, 44, (5) pp. 545-551. ISSN 1061-4036 (2012) [Refereed Article]


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Copyright 2012 the authors.

DOI: doi:10.1038/ng.2237

Abstract

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of < 4.0 x 10-7. In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 x 10-11) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 x 10-11). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 x 10-7) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 x 10-7); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association 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) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.

Item Details

Item Type:Refereed Article
Keywords:GWAS, hippocampus, aging
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Medical Genetics (excl. Cancer Genetics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Inherited Diseases (incl. Gene Therapy)
Author:Srikanth, V (Dr Velandai Srikanth)
Author:Stankovich, J (Dr Jim Stankovich)
Author:Thomson, R (Dr Russell Thomson)
ID Code:77486
Year Published:2012
Web of Science® Times Cited:102
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-04-19
Last Modified:2013-04-16
Downloads:0

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