Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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; Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium; 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; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.
Common variants at 12q14 and 12q24 are associated with hippocampal volume.
Nat Genet. 2012; 44(5):545-551
Doi: 10.1038/ng.2237
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- Co-Autor*innen der Med Uni Graz
- Cavalieri Margherita
- Enzinger Christian
- Fazekas Franz
- Schmidt Helena
- Schmidt Reinhold
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- 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 × 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Alzheimer Disease - genetics
- Chromosomes, Human, Pair 12 - genetics
- Cognition Disorders - genetics
- Dementia - genetics
- Genetic Loci -
- Genetic Markers -
- Genome-Wide Association Study -
- Hippocampus - physiopathology
- Humans -
- Meta-Analysis as Topic -
- Polymorphism, Single Nucleotide - genetics