Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy

Leslie M. Ramirez, Naira Goukasian, Shai Porat, Kristy S. Hwang, Jennifer A. Eastman, Sona Hurtz, Benjamin Wang, Nouchee Vang, Renee Sears, Eric Klein, Giovanni Coppola, Liana G. Apostolova

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The precise physiologic function of many of the recently discovered Alzheimer's disease risk variants remains unknown. The downstream effects of genetic variants remain largely unexplored. We studied the relationship between the top 10 non-APOE genes with cortical and hippocampal atrophy as markers of neurodegeneration using 1.5T magnetic resonance imaging, 1-million single nucleotide polymorphism Illumina Human Omni-Quad array and Illumina Human BeadChip peripheral blood expression array data on 50 cognitively normal and 98 mild cognitive impairment subjects. After explicit matching of cortical and hippocampal morphology, we computed in 3D, the cortical thickness and hippocampal radial distance measures for each participant. Associations between the top 10 non-APOE genome-wide hits and neurodegeneration were explored using linear regression. Map-wise statistical significance was determined with permutations using threshold of p < 0.01. MS4A6A rs610932 and ABCA7 rs3764650 demonstrated significant associations with cortical and hippocampal atrophy. Exploratory MS4A6A and ABCA7 peripheral blood expression analyses revealed a similar pattern of associations with cortical neurodegeneration. To our knowledge, this is the first report of the effect of ABCA7 and MS4A6A on neurodegeneration.

Original languageEnglish (US)
Pages (from-to)82-89
Number of pages8
JournalNeurobiology of Aging
Volume39
DOIs
StatePublished - Mar 1 2016

Keywords

  • AD risk genes
  • Alzheimer's disease
  • Cortical atrophy
  • Cortical thickness
  • Hippocampal atrophy
  • Neurodegeneration

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy'. Together they form a unique fingerprint.

  • Cite this

    Ramirez, L. M., Goukasian, N., Porat, S., Hwang, K. S., Eastman, J. A., Hurtz, S., Wang, B., Vang, N., Sears, R., Klein, E., Coppola, G., & Apostolova, L. G. (2016). Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy. Neurobiology of Aging, 39, 82-89. https://doi.org/10.1016/j.neurobiolaging.2015.10.037