Estimation of a significance threshold for epigenome-wide association studies.
Genet Epidemiol
; 42(1): 20-33, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29034560
ABSTRACT
Epigenome-wide association studies (EWAS) are designed to characterise population-level epigenetic differences across the genome and link them to disease. Most commonly, they assess DNA-methylation status at cytosine-guanine dinucleotide (CpG) sites, using platforms such as the Illumina 450k array that profile a subset of CpGs genome wide. An important challenge in the context of EWAS is determining a significance threshold for declaring a CpG site as differentially methylated, taking multiple testing into account. We used a permutation method to estimate a significance threshold specifically for the 450k array and a simulation extrapolation approach to estimate a genome-wide threshold. These methods were applied to five different EWAS datasets derived from a variety of populations and tissue types. We obtained an estimate of α=2.4×10-7 for the 450k array, and a genome-wide estimate of α=3.6×10-8. We further demonstrate the importance of these results by showing that previously recommended sample sizes for EWAS should be adjusted upwards, requiring samples between â¼10% and â¼20% larger in order to maintain type-1 errors at the desired level.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma Humano
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Ilhas de CpG
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Metilação de DNA
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Epigênese Genética
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Estudo de Associação Genômica Ampla
Tipo de estudo:
Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Humans
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Infant
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article