PMID- 26292806 OWN - NLM STAT- MEDLINE DCOM- 20160519 LR - 20240306 IS - 1756-994X (Electronic) IS - 1756-994X (Linking) VI - 7 IP - 1 DP - 2015 Aug 21 TI - DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection. PG - 89 LID - 10.1186/s13073-015-0213-8 [doi] LID - 89 AB - 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). FAU - Everson, Todd M AU - Everson TM AD - 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. FAU - Lyons, Genevieve AU - Lyons G AD - Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Pickens Tower, 1400 Pressler, Houston, TX, 77230, USA. FAU - Zhang, Hongmei AU - Zhang H AD - Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN, 38152, USA. FAU - Soto-Ramirez, Nelis AU - Soto-Ramirez N AD - Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN, 38152, USA. FAU - Lockett, Gabrielle A AU - Lockett GA AD - Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK. FAU - Patil, Veeresh K AU - Patil VK AD - The David Hide Asthma and Allergy Research Centre, St Mary's, Hospital, Parkhurst Road, Newport, Isle of Wight, PO30 5TG, UK. FAU - Merid, Simon K AU - Merid SK AD - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Soderhall, Cilla AU - Soderhall C AD - Department of Biosciences and Nutrition, and Center for Innovative Medicine (CIMED), Karolinska Institutet, 141 83, Stockholm, Sweden. FAU - Melen, Erik AU - Melen E AD - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. AD - Sachs' Children's Hospital, Stockholm, Sweden. FAU - Holloway, John W AU - Holloway JW AD - Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK. AD - Clinical and Experimental Sciences and NIHR Respiratory Biomedical Research Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK. FAU - Arshad, S Hasan AU - Arshad SH AD - The David Hide Asthma and Allergy Research Centre, St Mary's, Hospital, Parkhurst Road, Newport, Isle of Wight, PO30 5TG, UK. AD - Clinical and Experimental Sciences and NIHR Respiratory Biomedical Research Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK. FAU - Karmaus, Wilfried AU - Karmaus W AD - Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN, 38152, USA. LA - eng GR - 090532/Z/09/Z/WT_/Wellcome Trust/United Kingdom GR - G0900747/MRC_/Medical Research Council/United Kingdom GR - R01 AI061471/AI/NIAID NIH HHS/United States GR - R01 AI091905/AI/NIAID NIH HHS/United States GR - G0900747 91070/MRC_/Medical Research Council/United Kingdom GR - R01 HL082925/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150821 PL - England TA - Genome Med JT - Genome medicine JID - 101475844 RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Adolescent MH - Cohort Studies MH - CpG Islands MH - *DNA Methylation MH - Female MH - Genetic Loci MH - Genome, Human MH - Humans MH - Hypersensitivity, Immediate/*blood/diagnosis/epidemiology/*genetics MH - Immunoglobulin E/*blood MH - Male MH - Prevalence MH - Skin Tests MH - United Kingdom/epidemiology PMC - PMC4545869 EDAT- 2015/08/22 06:00 MHDA- 2016/05/20 06:00 PMCR- 2015/08/21 CRDT- 2015/08/22 06:00 PHST- 2014/06/16 00:00 [received] PHST- 2015/08/03 00:00 [accepted] PHST- 2015/08/22 06:00 [entrez] PHST- 2015/08/22 06:00 [pubmed] PHST- 2016/05/20 06:00 [medline] PHST- 2015/08/21 00:00 [pmc-release] AID - 10.1186/s13073-015-0213-8 [pii] AID - 213 [pii] AID - 10.1186/s13073-015-0213-8 [doi] PST - epublish SO - Genome Med. 2015 Aug 21;7(1):89. doi: 10.1186/s13073-015-0213-8.