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Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis
- Source :
- NPJ Genomic Medicine, npj Genomic Medicine, Vol 5, Iss 1, Pp 1-9 (2020)
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group UK, 2020.
-
Abstract
- We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor.
- Subjects :
- 0301 basic medicine
amyotrophic lateral sclerosis
medicine.medical_specialty
lcsh:QH426-470
lcsh:Medicine
Predictive markers
Gastroenterology
Article
03 medical and health sciences
0302 clinical medicine
single nucleotide polymorphism
Internal medicine
Genetics
Medicine
Amyotrophic lateral sclerosis
Molecular Biology
Genetics (clinical)
DNA methylation
business.industry
lcsh:R
Confounding
Area under the curve
Methylation
cohort analysis
medicine.disease
lcsh:Genetics
030104 developmental biology
Out of sample
Cohort
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20567944
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- NPJ Genomic Medicine
- Accession number :
- edsair.doi.dedup.....8fa79cc0712b689bee7e14f5acbf7863