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

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) re...

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Detalles Bibliográficos
Autores principales: Bis, Joshua C., DeCarli, Charles, Smith, Albert Vernon, van der Lijn, Fedde, Crivello, Fabrice, Fornage, Myriam, Debette, Stephanie, Shulman, Joshua M., 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., Chibnik, Lori B., 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, Breteler, Monique M.B., De Jager, Philip L., 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427729/
https://www.ncbi.nlm.nih.gov/pubmed/22504421
http://dx.doi.org/10.1038/ng.2237
Descripción
Sumario: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.

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