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
Epigenomicsjournal_title
Epigenomicsauthors
Popovic M,Fasanelli F,Fiano V,Biggeri A,Richiardi Ldoi
10.2217/epi-2017-0073subject
Has Abstractpub_date
2017-12-01 00:00:00pages
1489-1502issue
12eissn
1750-1911issn
1750-192Xjournal_volume
9pub_type
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