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Logo of bmcgenoBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Genomics
 
BMC Genomics. 2009; 10: 405.
Published online Aug 27, 2009. doi:  10.1186/1471-2164-10-405
PMCID: PMC2743717
Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients
Christiaan GJ Saris,#1 Steve Horvath,corresponding author#2,3 Paul WJ van Vught,#1 Michael A van Es,1 Hylke M Blauw,1 Tova F Fuller,2 Peter Langfelder,2,3 Joseph DeYoung,4 John HJ Wokke,1 Jan H Veldink,1 Leonard H van den Berg,corresponding author1 and Roel A Ophoffcorresponding author2,4,5
1Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands
2Department of Human Genetics, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
3Department of Biostatistics, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
4Semel Institute of Neuroscience and Human Behavioral, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
5Department of Medical Genetics and Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht 3584 CG, the Netherlands
corresponding authorCorresponding author.
#Contributed equally.
Christiaan GJ Saris: c.g.j.saris/at/umcutrecht.nl; Steve Horvath: shorvath/at/mednet.ucla.edu; Paul WJ van Vught: P.W.J.vanVught/at/umcutrecht.nl; Michael A van Es: m.a.vanes/at/umcutrecht.nl; Hylke M Blauw: h.blauw/at/umcutrecht.nl; Tova F Fuller: msmudphud/at/gmail.com; Peter Langfelder: peter.langfelder/at/gmail.com; Joseph DeYoung: JDeYoung/at/mednet.ucla.edu; John HJ Wokke: J.Wokke/at/umcutrecht.nl; Jan H Veldink: jveldink/at/umcutrecht.nl; Leonard H van den Berg: lberg/at/umcutrecht.nl; Roel A Ophoff: rophoff/at/mednet.ucla.edu
Received March 16, 2009; Accepted August 27, 2009.
Abstract
Background
Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients.
Results
Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%) showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA) was used to find disease-related networks (modules) and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls) and third dataset (63 patients and 63 controls), thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS.
Conclusion
This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.
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