Genetic Variation and Neuroimaging Measures in Alzheimer Disease

被引：172

作者：

Biffi, Alessandro ^{[1
,3
]}

Anderson, Christopher D. ^{[1
,3
]}

Desikan, Rahul S. ^{[2
]}

Sabuncu, Mert ^{[2
]}

Cortellini, Lynelle ^{[1
,2
,3
]}

Schmansky, Nick ^{[2
]}

Salat, David ^{[2
]}

Rosand, Jonathan ^{[1
,3
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA

[3] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

来源：

ARCHIVES OF NEUROLOGY | 2010年 / 67卷 / 06期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SURFACE-BASED ANALYSIS; IDENTIFIES VARIANTS; HIPPOCAMPAL ATROPHY; BRAIN; SEGMENTATION; BIN1; CLU;

D O I：

10.1001/archneurol.2010.108

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: To investigate whether genome-wide association study (GWAS) validated and GWAS-promising candidate loci influence magnetic resonance imaging measures and clinical Alzheimer's disease (AD) status. Design: Multicenter case-control study of genetic and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative. Setting: Multicenter GWAS. Patients: A total of 168 individuals with probable AD, 357 with mild cognitive impairment, and 215 cognitively normal control individuals recruited from more than 50 Alzheimer's Disease Neuroimaging Initiative centers in the United States and Canada. All study participants had APOE and genome-wide genetic data available. Main Outcome Measures: We investigated the influence of GWAS-validated and GWAS-promising novel AD loci on hippocampal volume, amygdala volume, white matter lesion volume, entorhinal cortex thickness, parahippocampal gyrus thickness, and temporal pole cortex thickness. Results: Markers at the APOE locus were associated with all phenotypes except white matter lesion volume (all false discovery rate corrected P values < .001). Novel and established AD loci identified by prior GWASs showed a significant cumulative score based effect (false discovery rate P = .04) on all analyzed neuroimaging measures. The GWAS-validated variants at the CR1 and PICALM loci and markers at 2 novel loci (BIN1 and CNTN5) showed association with multiple magnetic resonance imaging characteristics (false discovery rate P < .05). Conclusions: Loci associated with AD also influence neuroimaging correlates of this disease. Furthermore, neuroimaging analysis identified 2 additional loci of high interest for further study.

引用

页码：677 / 685

页数：9

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