Common variants at 12q14 and 12q24 are associated with hippocampal volume
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 × 10−7. In two additional sampl...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2012
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| In: |
Nature genetics
Year: 2012, Volume: 44, Issue: 5, Pages: 545-551 |
| ISSN: | 1546-1718 |
| DOI: | 10.1038/ng.2237 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/ng.2237 Verlag, Volltext: https://www.nature.com/articles/ng.2237 
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| Author Notes: | Joshua C. Bis, Charles DeCarli, Albert Vernon Smith, Fedde van der Lijn, Fabrice Crivello, Myriam Fornage, Stephanie Debette, Joshua M. Shulman, Helena Schmidt, Velandai Srikanth, Maaike Schuur, Lei Yu, Seung-Hoan Choi, Sigurdur Sigurdsson, Benjamin F. J. Verhaaren, Anita L. DeStefano, Jean-Charles Lambert, Clifford R. Jack Jr, Maksim Struchalin, Jim Stankovich, Carla A. Ibrahim-Verbaas, Debra Fleischman, Alex Zijdenbos, Tom den Heijer, Bernard Mazoyer, Laura H. Coker, Christian Enzinger, Patrick Danoy, Najaf Amin, Konstantinos Arfanakis, Mark A. van Buchem, Renée F. A. G. de Bruijn, Alexa Beiser, Carole Dufouil, Juebin Huang, Margherita Cavalieri, Russell Thomson, Wiro J. Niessen, Lori B. Chibnik, Gauti K. Gislason, Albert Hofman, Aleksandra Pikula, Philippe Amouyel, Kevin B. Freeman, Thanh G. Phan, Ben A. Oostra, Jason L. Stein, Sarah E. Medland, Alejandro Arias Vasquez, Derrek P. Hibar, Margaret J. Wright, Barbara Franke, Nicholas G. Martin, Paul M. Thompson, Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium, Michael A. Nalls, Andre G. Uitterlinden, Rhoda Au, Alexis Elbaz, Richard J. Beare, John C. van Swieten, Oscar L. Lopez, Tamara B. Harris, Vincent Chouraki, Monique M. B. Breteler, Philip L. De Jager, James T. Becker, Meike W. Vernooij, David Knopman, Franz Fazekas, Philip A. Wolf, Aad van der Lugt, Vilmundur Gudnason, W. T. Longstreth Jr, Matthew A. Brown, David A. Bennett, Cornelia M. van Duijn, Thomas H. Mosley, Reinhold Schmidt, Christophe Tzourio, Lenore J. Launer, M. Arfan Ikram, Sudha Seshadri for the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Knut Schnell und andere 192 Kollaboratoren |
| Summary: | 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 × 10−7. In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10−11) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10−11). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10−7) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 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. |
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| Item Description: | Published online 15 April 2012 Gesehen am 05.10.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1546-1718 |
| DOI: | 10.1038/ng.2237 |