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Multicenter Study
. 2010 Jun;67(6):677-85.
doi: 10.1001/archneurol.2010.108.

Genetic variation and neuroimaging measures in Alzheimer disease

Alessandro Biffi  1 , Christopher D Anderson, Rahul S Desikan, Mert Sabuncu, Lynelle Cortellini, Nick Schmansky, David Salat, Jonathan Rosand; Alzheimer's Disease Neuroimaging Initiative (ADNI)
Affiliations
Multicenter Study

Genetic variation and neuroimaging measures in Alzheimer disease

Alessandro Biffi et al. Arch Neurol. 2010 Jun.

Abstract

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.

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Figures

Figure
Figure
Genotype data quality control for the Alzheimer’s Disease Neuroimaging Initiative (ADNI) genome-wide association study (GWAS) data set. Single-nucleotide polymorphism (SNPs) may have met multiple filtering criteria. AD indicates Alzheimer disease; BP, blood pressure; CNV, copy number variation; HWE, Hardy-Weinberg equilibrium; IBS, identity by state; LD, linkage disequilibrium; MAF, minor allele frequency; MCI, mild cognitive impairment; PCA, principal component analysis; prop. diff., proportional between-individuals difference as determined by identity by state; and QC, quality control.
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