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

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Author
Bis, Joshua C.
DeCarli, Charles
Smith, Albert Vernon
van der Lijn, Fedde
Crivello, Fabrice
Fornage, Myriam
Debette, Stephanie
Schmidt, Helena
Srikanth, Velandai
Schuur, Maaike
Yu, Lei
Choi, Seung-Hoan
Sigurdsson, Sigurdur
Verhaaren, Benjamin F.J.
DeStefano, Anita L.
Lambert, Jean-Charles
Jack, Clifford R.
Struchalin, Maksim
Stankovich, Jim
Ibrahim-Verbaas, Carla A.
Fleischman, Debra
Zijdenbos, Alex
den Heijer, Tom
Mazoyer, Bernard
Coker, Laura H.
Enzinger, Christian
Danoy, Patrick
Amin, Najaf
Arfanakis, Konstantinos
van Buchem, Mark A.
de Bruijn, Renée F.A.G.
Beiser, Alexa
Dufouil, Carole
Huang, Juebin
Cavalieri, Margherita
Thomson, Russell
Niessen, Wiro J.
Gislason, Gauti K.
Hofman, Albert
Pikula, Aleksandra
Amouyel, Philippe
Freeman, Kevin B.
Phan, Thanh G.
Oostra, Ben A.
Stein, Jason L.
Medland, Sarah E.
Vasquez, Alejandro Arias
Hibar, Derrek P.
Wright, Margaret J.
Franke, Barbara
Martin, Nicholas G.
Thompson, Paul M.
Nalls, Michael A.
Uitterlinden, Andre G.
Au, Rhoda
Elbaz, Alexis
Beare, Richard J.
van Swieten, John C.
Lopez, Oscar
Harris, Tamara B.
Chouraki, Vincent
Becker, James T.
Vernooij, Meike W.
Knopman, David
Fazekas, Franz
Wolf, Philip A.
van der Lugt, Aad
Gudnason, Vilmundur
Longstreth, W.T.
Brown, Mathew A.
Bennett, David A.
van Duijn, Cornelia M.
Mosley, Thomas H.
Schmidt, Reinhold
Tzourio, Christophe
Launer, Lenore J.
Ikram, M. Arfan
Seshadri, Sudha
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ng.2237Metadata
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Bis, Joshua C., Charles DeCarli, Albert Vernon Smith, Fedde van der Lijn, Fabrice Crivello, Myriam Fornage, Stephanie Debette, et al. 2012. Common variants at 12q14 and 12q24 are associated with hippocampal volume. Nature Genetics 44(5): 545-551.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427729/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579383
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