Arne De Roeck|Christine Van Broeckhoven|Kristel Sleegers
The role of ABCA7 in Alzheimer’s disease: evidence from genomics, transcriptomics and methylomics
VIB-UAntwerp Center for Molecular Neurology|University of Antwerp|VIB-UAntwerp Center for Molecular Neurology|University of Antwerp|VIB-UAntwerp Center for Molecular Neurology|University of Antwerp
genomewide association studies gwas originally identified atpbinding cassette subfamily member 7 abca7 novel risk gene alzheimers disease ad since accumulating evidence vitro vivo humanbased studies corroborated extended association promoting abca7 one important risk genes earlyonset lateonset ad harboring common rare risk variants relatively large effect ad risk within review provide comprehensive assessment literature abca7 focus adrelated human omics studies eg genomics transcriptomics methylomics european african american populations indirect abca7 gwas associations explained expansion abca7 variable number tandem repeat vntr common premature termination codon ptc variant respectively rare abca7 ptc variants strongly enriched ad patients displayed inheritance patterns resembling autosomal dominant ad addition rare missense variants frequent ad patients healthy controls whereas common abca7 missense variant may protect disease methylation several cpg sites abca7 locus significantly associated ad furthermore abca7 contains many different isoforms abca7 splicing shown associate ad besides associations disease status genetic epigenetic abca7 markers also showed significant correlations ad endophenotypes particular amyloid deposition brain morphology conclusion humanbased omics studies provide converging evidence partial abca7 loss ad pathomechanism future studies make clear interventions abca7 expression serve valuable therapeutic target ad