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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 prevalences of allergic diseases are increasing worldwide, emphasizing the need to elucidate their pathogeneses. The aim of this study was to use a two-stage design to identify DNA methylation (DNA-M) levels at cytosine-phosphate-guanine (CpG) sites across the genome associated with atopy and high serum IgE, then to replicate our findings in an independent cohort. Methods: Atopy was measured via skin prick tests and high serum IgE. Methylation levels were measured from whole blood using the Illumina Infinium HumanMethylation450 BeadChip among 18-year-old females (n=245) and males (n=122) in the Isle of Wight (IOW) birth cohort. After data cleaning, processing and removing probes with possible SNPs, DNA-M levels from 254,460 CpG sites from the female samples were subjected to recursive Random Forest (RF) 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 regressions 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: 6.5*10-9 to 1.4*10-5) and 12 associated with high IgE levels (P-value range: 1.1*10-5 to 7.1*10-4) at the Bonferroni adjusted ? (0.05/62 = 0.0008). 13 out of 19 available sites 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).
University of Southampton
Everson, Todd M.
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Lyons, Genevieve
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Zhang, Hongmei
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Soto-Ramírez, Nelís
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Lockett, Gabrielle
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Patil, Veeresh, Keshirajagowda
b898b9a7-db31-4c1c-b0f0-4165b3e4d29c
Merid, Simon K.
c7eb7686-d1e1-45ed-93e3-e9f3e85ce197
Söderhäll, Cilla
5117b3f6-4192-4cd7-b81f-427bead07bd0
Melén, Eric
2186e32f-4d44-4c7d-aebb-36c2e8777b9c
Holloway, John
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Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wifried
654ee712-cda8-469a-b1e9-4fdc5347a55c
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
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Patil, Veeresh, Keshirajagowda
b898b9a7-db31-4c1c-b0f0-4165b3e4d29c
Merid, Simon K.
c7eb7686-d1e1-45ed-93e3-e9f3e85ce197
Söderhäll, Cilla
5117b3f6-4192-4cd7-b81f-427bead07bd0
Melén, Eric
2186e32f-4d44-4c7d-aebb-36c2e8777b9c
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wifried
654ee712-cda8-469a-b1e9-4fdc5347a55c

Everson, Todd M., Lyons, Genevieve, Zhang, Hongmei, Soto-Ramírez, Nelís, Lockett, Gabrielle, Patil, Veeresh, Keshirajagowda, Merid, Simon K., Söderhäll, Cilla, Melén, Eric, Holloway, John, Arshad, Syed and Karmaus, Wifried (2015) DNA methylation loci associated with atopy and high serum IgE: A genome-wide application of recursive random forest feature selection. University of Southampton doi:10.5258/SOTON/379389 [Dataset]

Record type: Dataset

Abstract

Background: The prevalences of allergic diseases are increasing worldwide, emphasizing the need to elucidate their pathogeneses. The aim of this study was to use a two-stage design to identify DNA methylation (DNA-M) levels at cytosine-phosphate-guanine (CpG) sites across the genome associated with atopy and high serum IgE, then to replicate our findings in an independent cohort. Methods: Atopy was measured via skin prick tests and high serum IgE. Methylation levels were measured from whole blood using the Illumina Infinium HumanMethylation450 BeadChip among 18-year-old females (n=245) and males (n=122) in the Isle of Wight (IOW) birth cohort. After data cleaning, processing and removing probes with possible SNPs, DNA-M levels from 254,460 CpG sites from the female samples were subjected to recursive Random Forest (RF) 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 regressions 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: 6.5*10-9 to 1.4*10-5) and 12 associated with high IgE levels (P-value range: 1.1*10-5 to 7.1*10-4) at the Bonferroni adjusted ? (0.05/62 = 0.0008). 13 out of 19 available sites 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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Published date: 2015
Organisations: Epigenetics, Clinical & Experimental Sciences, Faculty of Medicine, Human Development & Health

Identifiers

Local EPrints ID: 379389
URI: http://eprints.soton.ac.uk/id/eprint/379389
PURE UUID: 5007d493-677b-4315-a47f-0dc0c6614c67
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 27 Jul 2015 15:32
Last modified: 15 Apr 2021 01:36

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Contributors

Creator: Todd M. Everson
Creator: Genevieve Lyons
Creator: Hongmei Zhang
Creator: Nelís Soto-Ramírez
Creator: Gabrielle Lockett
Creator: Veeresh, Keshirajagowda Patil
Creator: Simon K. Merid
Creator: Cilla Söderhäll
Creator: Eric Melén
Creator: John Holloway ORCID iD
Creator: Syed Arshad
Creator: Wifried Karmaus

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