Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes

Ashley R Jones, Claire Troakes, Andrew King, Vibhu Sahni, Simone De Jong, Koen Bossers, Efterpi Papouli, Muddassar Mirza, Safa Al-Sarraj, Christopher E Shaw, Pamela J Shaw, Janine Kirby, Jan H Veldink, Jeffrey D Macklis, John F Powell, Ammar Al-Chalabi

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10(-5)). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10(-3)), MATR3 (p = 3.46 × 10(-3)), and VEGFA (p = 8.21 × 10(-4)), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison.

Original languageEnglish
Pages (from-to)2006.e1-2006.e9
Number of pages9
JournalNeurobiology of Aging
Early online date19 Feb 2015
DOIs
Publication statusE-pub ahead of print - 19 Feb 2015

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