title: A statistical method for excluding non-variable CpG sites in high-throughput DNA methylation profiling.
abstract: BACKGROUND
  High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called "non-variable sites" will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers.
  
  
  RESULTS
  We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites from further analyses. Our method is illustrated using data obtained by hybridizing DNA extracted from the peripheral blood mononuclear cells of 311 samples to an array assaying 1505 CpG sites. Results showed that a large proportion of the CpG sites did not show inter-individual variation in methylation.
  
  
  CONCLUSIONS
  Our method resulted in a substantial improvement in association signals between methylation sites and outcome variables while controlling the false discovery rate at the same level.
authors.affiliation: Altria Client Services, Research Development & Engineering, Richmond, VA 23219, USA. hlmeng@yahoo.com
authors.forename: Hailong
authors.initials: H
authors.lastname: Meng
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Joyce
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Adkins
authors.forename: Priyadarshi
authors.initials: P
authors.lastname: Basu
authors.forename: Yankai
authors.initials: Y
authors.lastname: Jia
authors.forename: Guoya
authors.initials: G
authors.lastname: Li
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Sengupta
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Zedler
authors.forename: E Lenn
authors.initials: EL
authors.lastname: Murrelle
authors.forename: Edwin J C G
authors.initials: EJ
authors.lastname: van den Oord
mesh_terms: D018899:CpG Islands / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D015233:Models, Statistical
chemical_list: D004247:DNA