title: DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection.
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).
authors: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene Street, Columbia, SC, 29208, USA. everson.rsrch@gmail.com.
authors: Todd M
authors: TM
authors: Everson
authors: Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Pickens Tower, 1400 Pressler, Houston, TX, 77230, USA.
authors: Genevieve
authors: G
authors: Lyons
authors: Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN, 38152, USA.
authors: Hongmei
authors: H
authors: Zhang
authors: Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN, 38152, USA.
authors: Nelís
authors: N
authors: Soto-Ramírez
authors: Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.
authors: Gabrielle A
authors: GA
authors: Lockett
authors: The David Hide Asthma and Allergy Research Centre, St Mary's, Hospital, Parkhurst Road, Newport, Isle of Wight, PO30 5TG, UK.
authors: Veeresh K
authors: VK
authors: Patil
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Simon K
authors: SK
authors: Merid
authors: Department of Biosciences and Nutrition, and Center for Innovative Medicine (CIMED), Karolinska Institutet, 141 83, Stockholm, Sweden.
authors: Cilla
authors: C
authors: Söderhäll
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.|Sachs' Children's Hospital, Stockholm, Sweden.
authors: Erik
authors: E
authors: Melén
authors: Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.|Clinical and Experimental Sciences and NIHR Respiratory Biomedical Research Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.
authors: John W
authors: JW
authors: Holloway
authors: The David Hide Asthma and Allergy Research Centre, St Mary's, Hospital, Parkhurst Road, Newport, Isle of Wight, PO30 5TG, UK.|Clinical and Experimental Sciences and NIHR Respiratory Biomedical Research Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.
authors: S Hasan
authors: SH
authors: Arshad
authors: Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN, 38152, USA.
authors: Wilfried
authors: W
authors: Karmaus
mesh_terms: D000293:Adolescent; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood*; D008297:Male; D015995:Prevalence; D012882:Skin Tests; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D007073:Immunoglobulin E