| Literature DB >> 33579987 |
Jian Yang1,2, Ian P Blair3, Allan F McRae1,2, Naomi R Wray4,5, Marta F Nabais1,6, Tian Lin1, Beben Benyamin1,7, Kelly L Williams3, Fleur C Garton1, Anna A E Vinkhuyzen1, Futao Zhang1, Costanza L Vallerga1, Restuadi Restuadi1, Anna Freydenzon1, Ramona A J Zwamborn8, Paul J Hop8, Matthew R Robinson1, Jacob Gratten1,9, Peter M Visscher1,2, Eilis Hannon6, Jonathan Mill6,10, Matthew A Brown11, Nigel G Laing12,13, Karen A Mather14,15, Perminder S Sachdev14,16, Shyuan T Ngo2,17,18, Frederik J Steyn17,18, Leanne Wallace1, Anjali K Henders1, Merrilee Needham19,20,21, Jan H Veldink8, Susan Mathers22, Garth Nicholson23, Dominic B Rowe3, Robert D Henderson2,18,24, Pamela A McCombe18,24, Roger Pamphlett25.
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.Year: 2020 PMID： 33579987 DOI： 10.1038/s41525-020-0118-3
Source DB: PubMed Journal: NPJ Genom Med ISSN： 2056-7944 Impact factor: 8.617