Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis.

NPJ Genomic Medicine
Marta F NabaisNaomi R Wray

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.

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Citations

Jun 23, 2020·Expert Review of Neurotherapeutics·Pamela A McCombeRobert D Henderson
Dec 12, 2020·Free Radical Biology & Medicine·Fabio Coppedè
Oct 15, 2020·JAMA Psychiatry·Graham K MurrayNaomi R Wray

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Datasets Mentioned

BETA
NA06997
NA07029

Methods Mentioned

BETA
chip

Software Mentioned

MWAS
GENCODE
GCTA
MOA
AU
OSCA
- data - based Complex trait Analysis ( OSCA )
OmicS
GREML
R package pROC

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Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.