Journal
NAR GENOMICS AND BIOINFORMATICS
Volume 2, Issue 4, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nargab/lqaa105
Keywords
-
Funding
- ALS Foundation Netherlands
- MND Association (UK)
- European Research Council [772376-EScORIAL]
- Health Holland, Top Sector Life Sciences Health
- EU Joint Programme-Neurodegenerative Disease Research (JPND) project
- Medical Research Council [MR/L501529/1, MR/R024804/1, 733051071, K013807]
- Motor Neurone Disease Association
- National Institute for Health Research (NIHR)
- Maudsley Biomedical Research Centre
- MND Association
- Wellcome Trust
- NIHR
- Dementia Biomedical Research Unit and Biomedical Research Centre in Mental Health
- South London and Maudsley NHS Foundation Trust
- King's College London
- Science Foundation Ireland [17/CDA/4737]
- Medical Research Council Clinical Infrastructure Award [M008924]
- UK National DNA Bank for MND Research
- MRC [MR/R024804/1, MR/M008924/1, MR/R005176/1, G0600974] Funding Source: UKRI
Ask authors/readers for more resources
Illumina DNA methylation arrays are a widely used tool for performing genome-wide DNA methylation analyses. However, measurements obtained from these arrays may be affected by technical artefacts that result in spurious associations if left unchecked. Cross-reactivity represents one of the major challenges, meaning that probes may map to multiple regions in the genome. Although several studies have reported on this issue, few studies have empirically examined the impact of cross-reactivity in an epigenome-wide association study (EWAS). In this paper, we report on cross-reactivity issues that we discovered in a large EWAS on the presence of the C9orf72 repeat expansion in ALS patients. Specifically, we found that that the majority of the significant probes inadvertently cross-hybridized to the C9orf72 locus. Importantly, these probes were not flagged as cross-reactive in previous studies, leading to novel insights into the extent to which cross-reactivity can impact EWAS. Our findings are particularly relevant for epigenetic studies into diseases associated with repeat expansions and other types of structural variation. More generally however, considering that most spurious associations were not excluded based on pre-defined sets of cross-reactive probes, we believe that the presented data-driven flag and consider approach is relevant for any type of EWAS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available