Genetic interactions associated with 12-month atrophy in hippocampus and entorhinal cortex in Alzheimer's Disease Neuroimaging Initiative

Shashwath A. Meda, Mary Ellen I. Koran, Jennifer Pryweller, Jennifer N. Vega, Tricia A. Thornton-Wells

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Missing heritability in late onset Alzheimer disease can be attributed, at least in part, to heterogeneity in disease status and to the lack of statistical analyses exploring genetic interactions. In the current study, we use quantitative intermediate phenotypes derived from magnetic resonance imaging data available from the Alzheimer's Disease Neuroimaging Initiative, and we test for association with gene-gene interactions within biological pathways. Regional brain volumes from the hippocampus (HIP) and entorhinal cortex (EC) were estimated from baseline and 12-month magnetic resonance imaging scans. Approximately 560,000 single nucleotide polymorphisms (SNPs) were available genome-wide. We tested all pairwise SNP-SNP interactions (approximately 151 million) within 212 Kyoto Encyclopedia of Genes and Genomes pathways for association with 12-month regional atrophy rates using linear regression, with sex, APOE ε4 carrier status, age, education, and clinical status as covariates. A total of 109 SNP-SNP interactions were associated with right HIP atrophy, and 125 were associated with right EC atrophy. Enrichment analysis indicated significant SNP-SNP interactions were overrepresented in the calcium signaling and axon guidance pathways for both HIP and EC atrophy and in the ErbB signaling pathway for HIP atrophy.

Original languageEnglish (US)
Pages (from-to)1518.e9-1518.e18
JournalNeurobiology of Aging
Volume34
Issue number5
DOIs
StatePublished - Jan 1 2013

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Entorhinal Cortex
Neuroimaging
Atrophy
Single Nucleotide Polymorphism
Hippocampus
Alzheimer Disease
Magnetic Resonance Imaging
Genome
Encyclopedias
Genes
Calcium Signaling
Linear Models
Phenotype
Education
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Genetic interactions associated with 12-month atrophy in hippocampus and entorhinal cortex in Alzheimer's Disease Neuroimaging Initiative. / Meda, Shashwath A.; Koran, Mary Ellen I.; Pryweller, Jennifer; Vega, Jennifer N.; Thornton-Wells, Tricia A.

In: Neurobiology of Aging, Vol. 34, No. 5, 01.01.2013, p. 1518.e9-1518.e18.

Research output: Contribution to journalArticle

Meda, Shashwath A. ; Koran, Mary Ellen I. ; Pryweller, Jennifer ; Vega, Jennifer N. ; Thornton-Wells, Tricia A. / Genetic interactions associated with 12-month atrophy in hippocampus and entorhinal cortex in Alzheimer's Disease Neuroimaging Initiative. In: Neurobiology of Aging. 2013 ; Vol. 34, No. 5. pp. 1518.e9-1518.e18.
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