Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort

A genome-wide, whole brain approach to investigate genetic effects on neuroimaging phenotypes for identifying quantitative trait loci is described. The Alzheimer's Disease Neuroimaging Initiative 1.5 T MRI and genetic dataset was investigated using voxel-based morphometry (VBM) and FreeSurfer p...

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Published in:NeuroImage (Orlando, Fla.) Fla.), 2010-11, Vol.53 (3), p.1051-1063
Main Authors: Shen, Li, Kim, Sungeun, Risacher, Shannon L., Nho, Kwangsik, Swaminathan, Shanker, West, John D., Foroud, Tatiana, Pankratz, Nathan, Moore, Jason H., Sloan, Chantel D., Huentelman, Matthew J., Craig, David W., DeChairo, Bryan M., Potkin, Steven G., Jack, Clifford R., Weiner, Michael W., Saykin, Andrew J.
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease - genetics
Alzheimer's disease
Apolipoproteins E - genetics
Automation
Cluster Analysis
Cognition Disorders - genetics
Databases, Factual
Female
Genetic Predisposition to Disease
Genetics
Genome-Wide Association Study
Genomes
Genomics
Genotype
Genotype & phenotype
Humans
Magnetic Resonance Imaging
Male
Medical imaging
Phenotype
Polymorphism, Single Nucleotide
Public private partnerships
Quantitative Trait Loci
Studies
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Summary:A genome-wide, whole brain approach to investigate genetic effects on neuroimaging phenotypes for identifying quantitative trait loci is described. The Alzheimer's Disease Neuroimaging Initiative 1.5 T MRI and genetic dataset was investigated using voxel-based morphometry (VBM) and FreeSurfer parcellation followed by genome-wide association studies (GWAS). One hundred forty-two measures of grey matter (GM) density, volume, and cortical thickness were extracted from baseline scans. GWAS, using PLINK, were performed on each phenotype using quality-controlled genotype and scan data including 530,992 of 620,903 single nucleotide polymorphisms (SNPs) and 733 of 818 participants (175 AD, 354 amnestic mild cognitive impairment, MCI, and 204 healthy controls, HC). Hierarchical clustering and heat maps were used to analyze the GWAS results and associations are reported at two significance thresholds (p
ISSN:1053-8119
1095-9572
DOI:10.1016/j.neuroimage.2010.01.042