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DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection

DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection
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 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)
89
Everson, Todd M.
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Lyons, Genevieve
1763ae2b-b78c-494d-8b0d-553f38446cab
Zhang, Hongmei
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Soto-Ramírez, Nelís
3526295b-e2ec-4cf3-bc74-088d10943f45
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Patil, Veeresh, Keshirajagowda
b898b9a7-db31-4c1c-b0f0-4165b3e4d29c
Merid, Simon K.
c7eb7686-d1e1-45ed-93e3-e9f3e85ce197
Sӧderhӓll, Cilla
15bc4f86-24e0-4e8c-9977-568d4e2661a8
Melén, Erik
c7ee5423-aed5-4905-80b3-65bc07192e0c
Holloway, John W.
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Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Everson, Todd M.
0639cdab-214c-4fd3-8181-bfca14ad58ef
Lyons, Genevieve
1763ae2b-b78c-494d-8b0d-553f38446cab
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Soto-Ramírez, Nelís
3526295b-e2ec-4cf3-bc74-088d10943f45
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Patil, Veeresh, Keshirajagowda
b898b9a7-db31-4c1c-b0f0-4165b3e4d29c
Merid, Simon K.
c7eb7686-d1e1-45ed-93e3-e9f3e85ce197
Sӧderhӓll, Cilla
15bc4f86-24e0-4e8c-9977-568d4e2661a8
Melén, Erik
c7ee5423-aed5-4905-80b3-65bc07192e0c
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853

Everson, Todd M., Lyons, Genevieve, Zhang, Hongmei, Soto-Ramírez, Nelís, Lockett, Gabrielle A., Patil, Veeresh, Keshirajagowda, Merid, Simon K., Sӧderhӓll, Cilla, Melén, Erik, Holloway, John W., Arshad, S. Hasan and Karmaus, Wilfried (2015) DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection. Genome Medicine, 7 (1), 89. (doi:10.1186/s13073-015-0213-8).

Record type: Article

Abstract

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)

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More information

Accepted/In Press date: 3 August 2015
Published date: 21 August 2015
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 380956
URI: https://eprints.soton.ac.uk/id/eprint/380956
PURE UUID: 7a6b24ab-aec0-411c-9a59-b6caef85de65
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 21 Sep 2015 12:54
Last modified: 06 Jun 2018 12:59

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