Increased correlation between methylation sites in epigenome-wide replication studies: impact on analysis and results.

Abstract:

AIM:To show that an increased correlation between CpGs after selection through an epigenome-wide association studies (EWAS) might translate into biased replication results. METHODS:Pairwise correlation coefficients between CpGs selected in two published EWAS, the top hits replication, Bonferroni p-values, Benjamini-Hochberg (BH) false discovery rate (FDR) and directional FDR r-values were calculated in the NINFEA cohort data. Exposures' random permutations were performed to show the empirical p-value distributions. RESULTS:The average pairwise correlation coefficients between CpGs were enhanced after selection for the replication (e.g., from 0.12 at genome-wide level to 0.26 among the selected CpGs), affecting the empirical p-value distributions and the usual multiple testing control. CONCLUSION:Bonferroni and Benjamini-Hochberg FDR are inappropriate for the EWAS replication phase, and methods that account for the underlying correlation need to be used.

journal_name

Epigenomics

journal_title

Epigenomics

authors

Popovic M,Fasanelli F,Fiano V,Biggeri A,Richiardi L

doi

10.2217/epi-2017-0073

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

1489-1502

issue

12

eissn

1750-1911

issn

1750-192X

journal_volume

9

pub_type

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