Cargando…
DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection
BACKGROUND: The prevalence of allergic diseases are increasing worldwide, emphasizing the need to elucidate their pathogeneses. The aims of this study were to use a two-stage design to identify DNA methylation levels at cytosine–phosphate–guanine (CpG) sites across the genome associated with atopy a...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545869/ https://www.ncbi.nlm.nih.gov/pubmed/26292806 http://dx.doi.org/10.1186/s13073-015-0213-8 |
_version_ | 1782386802479333376 |
---|---|
author | Everson, Todd M. Lyons, Genevieve Zhang, Hongmei Soto-Ramírez, Nelís Lockett, Gabrielle A. Patil, Veeresh K. Merid, Simon K. Sӧderhӓll, Cilla Melén, Erik Holloway, John W. Arshad, S. Hasan Karmaus, Wilfried |
author_facet | Everson, Todd M. Lyons, Genevieve Zhang, Hongmei Soto-Ramírez, Nelís Lockett, Gabrielle A. Patil, Veeresh K. Merid, Simon K. Sӧderhӓll, Cilla Melén, Erik Holloway, John W. Arshad, S. Hasan Karmaus, Wilfried |
author_sort | Everson, Todd M. |
collection | PubMed |
description | BACKGROUND: The prevalence of allergic diseases are increasing worldwide, emphasizing the need to elucidate their pathogeneses. The aims of this study were to use a two-stage design to identify DNA methylation levels at cytosine–phosphate–guanine (CpG) sites across the genome associated with atopy and high serum immunoglobulin E (IgE), then to replicate our findings in an independent cohort. METHODS: Atopy was assessed via skin prick tests and high serum IgE. Methylation levels were measured from whole blood using the Illumina Infinium HumanMethylation450 BeadChip from 18-year-old women (n = 245) and men (n = 122) in the Isle of Wight birth cohort. After data cleaning and processing, and removing probes with possible single nucleotide polymorphisms, DNA methylation levels from 254,460 CpG sites from the 245 women were subjected to recursive Random Forest feature selection for stage 1. The sites selected from stage 1 were tested in stage 2 for associations with atopy and high IgE levels (>200 kU/L) via logistic regression adjusted for predicted cell-type proportions and sex. Sites significantly associated with atopy in stage 2 underwent replication tests in the independent Swedish birth cohort BAMSE (n = 464). RESULTS: In stage 1, 62 sites were selected, of which 22 were associated with atopy in stage 2 (P-value range 6.5E−9 to 1.4E−5) and 12 associated with high IgE levels (P-value range 1.1E−5 to 7.1E−4) at the Bonferroni adjusted alpha (0.05/62 = 0.0008). Of the 19 available sites, 13 were replicated. CONCLUSIONS: We identified 13 novel epigenetic loci associated with atopy and high IgE that could serve as candidate loci for future studies; four were within genes with known roles in the immune response (cg04983687 in the body of ZFPM1, cg18219873 in the 5′UTR of PRG2, cg27469152 in the 3′UTR of EPX, and cg09332506 in the body of COPA). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0213-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4545869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45458692015-08-23 DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection Everson, Todd M. Lyons, Genevieve Zhang, Hongmei Soto-Ramírez, Nelís Lockett, Gabrielle A. Patil, Veeresh K. Merid, Simon K. Sӧderhӓll, Cilla Melén, Erik Holloway, John W. Arshad, S. Hasan Karmaus, Wilfried Genome Med Research BACKGROUND: The prevalence of allergic diseases are increasing worldwide, emphasizing the need to elucidate their pathogeneses. The aims of this study were to use a two-stage design to identify DNA methylation levels at cytosine–phosphate–guanine (CpG) sites across the genome associated with atopy and high serum immunoglobulin E (IgE), then to replicate our findings in an independent cohort. METHODS: Atopy was assessed via skin prick tests and high serum IgE. Methylation levels were measured from whole blood using the Illumina Infinium HumanMethylation450 BeadChip from 18-year-old women (n = 245) and men (n = 122) in the Isle of Wight birth cohort. After data cleaning and processing, and removing probes with possible single nucleotide polymorphisms, DNA methylation levels from 254,460 CpG sites from the 245 women were subjected to recursive Random Forest feature selection for stage 1. The sites selected from stage 1 were tested in stage 2 for associations with atopy and high IgE levels (>200 kU/L) via logistic regression adjusted for predicted cell-type proportions and sex. Sites significantly associated with atopy in stage 2 underwent replication tests in the independent Swedish birth cohort BAMSE (n = 464). RESULTS: In stage 1, 62 sites were selected, of which 22 were associated with atopy in stage 2 (P-value range 6.5E−9 to 1.4E−5) and 12 associated with high IgE levels (P-value range 1.1E−5 to 7.1E−4) at the Bonferroni adjusted alpha (0.05/62 = 0.0008). Of the 19 available sites, 13 were replicated. CONCLUSIONS: We identified 13 novel epigenetic loci associated with atopy and high IgE that could serve as candidate loci for future studies; four were within genes with known roles in the immune response (cg04983687 in the body of ZFPM1, cg18219873 in the 5′UTR of PRG2, cg27469152 in the 3′UTR of EPX, and cg09332506 in the body of COPA). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0213-8) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-21 /pmc/articles/PMC4545869/ /pubmed/26292806 http://dx.doi.org/10.1186/s13073-015-0213-8 Text en © Everson et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Everson, Todd M. Lyons, Genevieve Zhang, Hongmei Soto-Ramírez, Nelís Lockett, Gabrielle A. Patil, Veeresh K. Merid, Simon K. Sӧderhӓll, Cilla Melén, Erik Holloway, John W. Arshad, S. Hasan Karmaus, Wilfried DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection |
title | DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection |
title_full | DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection |
title_fullStr | DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection |
title_full_unstemmed | DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection |
title_short | DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection |
title_sort | dna methylation loci associated with atopy and high serum ige: a genome-wide application of recursive random forest feature selection |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545869/ https://www.ncbi.nlm.nih.gov/pubmed/26292806 http://dx.doi.org/10.1186/s13073-015-0213-8 |
work_keys_str_mv | AT eversontoddm dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT lyonsgenevieve dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT zhanghongmei dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT sotoramireznelis dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT lockettgabriellea dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT patilveereshk dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT meridsimonk dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT söderhällcilla dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT melenerik dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT hollowayjohnw dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT arshadshasan dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection AT karmauswilfried dnamethylationlociassociatedwithatopyandhighserumigeagenomewideapplicationofrecursiverandomforestfeatureselection |