Skip to main content

Advertisement

SpringerLink
Log in

Sex- and age-dependent DNA methylation at the 17q12-q21 locus associated with childhood asthma

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

An Erratum to this article was published on 14 April 2013

Abstract

Chromosomal region 17q12-q21 is one of the best-replicated genome-wide association study (GWAS) hits and associated with childhood-onset asthma. However, the mechanism by which the genetic association is restricted to childhood-onset disease is unclear. During childhood, more boys than girls develop asthma. Therefore, we tested the hypothesis that the 17q12-q21 genetic association was sex-specific. Indeed, a TDT test showed that in the Saguenay-Lac-Saint-Jean familial collection, the 17q12-q21 association was significant among male, but not among female asthmatic subjects. We next hypothesized that the bias in the genetic association resulted from sex-specific and/or age-dependent DNA methylation at regulatory regions and determined the methylation profiles of five 17q12-q21 gene promoters using the bisulfite sequencing methylation assay. We identified a single regulatory region within the zona pellucida binding protein 2 (ZPBP2) gene, which showed statistically significant differences between males and females with respect to DNA methylation. DNA methylation also varied with age and was higher in adult males compared to boys. We have recently identified two functionally important polymorphisms, both within the ZPBP2 gene that influence expression levels of neighboring genes. Combined with the results of the present work, these data converge pointing to the same 5 kb region within the ZPBP2 gene as a critical region for both gene expression regulation and predisposition to asthma. Our data show that sex- and age-dependent DNA methylation may act as a modifier of genetic effects and influence the results of genetic association studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • American Thoracic Society (1987) Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. Am Rev Respir Dis 136:225–244

    Google Scholar 

  • Aschard H, Bouzigon E, Corda E, Ulgen A, Dizier MH, Gormand F, Lathrop M, Kauffmann F, Demenais F (2009) Sex-specific effect of IL9 polymorphisms on lung function and polysensitization. Genes Immun 10:559–565. doi:10.1038/gene.2009.46

    Article  PubMed  CAS  Google Scholar 

  • Baccarelli A, Rusconi F, Bollati V, Catelan D, Accetta G, Hou L, Barbone F, Bertazzi PA, Biggeri A (2012) Nasal cell DNA methylation, inflammation, lung function and wheezing in children with asthma. Epigenomics 4:91–100. doi:10.2217/epi.11.106

    Article  PubMed  CAS  Google Scholar 

  • Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265. doi:10.1093/bioinformatics/bth457

    Article  PubMed  CAS  Google Scholar 

  • Begin P, Tremblay K, Daley D, Lemire M, Claveau S, Salesse C, Kacel S, Montpetit A, Becker A, Chan-Yeung M, Kozyrskyj AL, Hudson TJ, Laprise C (2007) Association of urokinase-type plasminogen activator with asthma and atopy. Am J Respir Crit Care Med 175:1109–1116. doi:10.1164/rccm.200607-1012OC

    Article  PubMed  CAS  Google Scholar 

  • Berlivet S, Moussette S, Ouimet M, Verlaan DJ, Koka V, Al Tuwaijri A, Kwan T, Sinnett D, Pastinen T, Naumova AK (2012) Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines. Hum Genet 131:1161–1171. doi:10.1007/s00439-012-1142-x

    Article  PubMed  CAS  Google Scholar 

  • Bouzigon E, Forabosco P, Koppelman GH, Cookson WO, Dizier MH, Duffy DL, Evans DM, Ferreira MA, Kere J, Laitinen T, Malerba G, Meyers DA, Moffatt M, Martin NG, Ng MY, Pignatti PF, Wjst M, Kauffmann F, Demenais F, Lewis CM (2010) Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy. Eur J Hum Genet 18:700–706. doi:10.1038/ejhg.2009.224

    Article  PubMed  CAS  Google Scholar 

  • Brauner EV, Loft S, Raaschou-Nielsen O, Vogel U, Andersen PS, Sorensen M (2011) Effects of a 17q21 chromosome gene variant, tobacco smoke and furred pets on infant wheeze. Genes Immun. doi:10.1038/gene.2011.51

    PubMed  Google Scholar 

  • Breton CV, Byun HM, Wang X, Salam MT, Siegmund K, Gilliland FD (2011) DNA methylation in the ARG-NOS pathway is associated with exhaled nitric oxide in asthmatic children. Am J Respir Crit Care Med p 21

  • Crosslin DR, McDavid A, Weston N, Nelson SC, Zheng X, Hart E, de Andrade M, Kullo IJ, McCarty CA, Doheny KF, Pugh E, Kho A, Hayes MG, Pretel S, Saip A, Ritchie MD, Crawford DC, Crane PK, Newton K, Li R, Mirel DB, Crenshaw A, Larson EB, Carlson CS, Jarvik GP (2011) Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network. Hum Genet. doi:10.1007/s00439-011-1103-9

    Google Scholar 

  • Dimas AS, Nica AC, Montgomery SB, Stranger BE, Raj T, Buil A, Giger T, Lappalainen T, Gutierrez-Arcelus M, Mu TC, McCarthy MI, Dermitzakis ET (2012) Sex-biased genetic effects on gene regulation in humans. Genome Res 22:2368–2375. doi:10.1101/gr.134981.111

    Article  PubMed  CAS  Google Scholar 

  • El-Maarri O, Walier M, Behne F, van Uum J, Singer H, Diaz-Lacava A, Nusgen N, Niemann B, Watzka M, Reinsberg J, van der Ven H, Wienker T, Stoffel-Wagner B, Schwaab R, Oldenburg J (2011) Methylation at global LINE-1 repeats in human blood are affected by gender but not by age or natural hormone cycles. PLoS ONE 6:e16252. doi:10.1371/journal.pone.0016252

    Article  PubMed  CAS  Google Scholar 

  • Ernst J, Kellis M (2010) Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat Biotechnol 28:817–825. doi:10.1038/nbt.1662

    Article  PubMed  CAS  Google Scholar 

  • Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, Zhang X, Wang L, Issner R, Coyne M, Ku M, Durham T, Kellis M, Bernstein BE (2010) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473:43–49. doi:10.1038/nature09906

    Article  Google Scholar 

  • Ferreira MA, Oates NA, van Vliet J, Zhao ZZ, Ehrich M, Martin NG, Montgomery GW, Whitelaw E, Duffy DL (2009) Characterization of the methylation patterns of MS4A2 in atopic cases and controls. Allergy 65:333–337

    Article  PubMed  Google Scholar 

  • Ferreira MA, McRae AF, Medland SE, Nyholt DR, Gordon SD, Wright MJ, Henders AK, Madden PA, Visscher PM, Wray NR, Heath AC, Montgomery GW, Duffy DL, Martin NG (2010) Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia. Eur J Hum Genet 19:458–464. doi:10.1038/ejhg.2010.191

    Article  PubMed  Google Scholar 

  • Flory JH, Sleiman PM, Christie JD, Annaiah K, Bradfield J, Kim CE, Glessner J, Imielinski M, Li H, Frackelton EC, Cuiping H, Otieno G, Thomas K, Smith R, Glaberson W, Garris M, Chiavacci R, Allen J, Spergel J, Grundmeier R, Grunstein M, Magnusson M, Grant SF, Bonnelykke K, Bisgaard H, Hakonarson H (2009) 17q12-21 variants interact with smoke exposure as a risk factor for pediatric asthma but are equally associated with early-onset versus late-onset asthma in North Americans of European ancestry. J Allergy Clin Immunol 124:605–607

    Article  PubMed  CAS  Google Scholar 

  • Fox S, Leitch AE, Duffin R, Haslett C, Rossi AG (2010) Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease. J Innate Immun 2:216–227. doi:10.1159/000284367

    Article  PubMed  CAS  Google Scholar 

  • Fu T, Pappou EP, Guzzetta AA, Jeschke J, Kwak R, Dave P, Hooker CM, Morgan R, Baylin SB, Iacobuzio-Donahue CA, Wolfgang CL, Ahuja N (2012) CpG island methylator phenotype-positive tumors in the absence of MLH1 methylation constitute a distinct subset of duodenal adenocarcinomas and are associated with poor prognosis. Clin Cancer Res 18:4743–4752. doi:10.1158/1078-0432.ccr-12-0707

    Article  PubMed  CAS  Google Scholar 

  • Halapi E, Gudbjartsson DF, Jonsdottir GM, Bjornsdottir US, Thorleifsson G, Helgadottir H, Williams C, Koppelman GH, Heinzmann A, Boezen HM, Jonasdottir A, Blondal T, Gudjonsson SA, Thorlacius T, Henry AP, Altmueller J, Krueger M, Shin HD, Uh ST, Cheong HS, Jonsdottir B, Ludviksson BR, Ludviksdottir D, Gislason D, Park CS, Deichmann K, Thompson PJ, Wjst M, Hall IP, Postma DS, Gislason T, Kong A, Jonsdottir I, Thorsteinsdottir U, Stefansson K (2010) A sequence variant on 17q21 is associated with age at onset and severity of asthma. Eur J Hum Genet 18:902–908

    Article  PubMed  CAS  Google Scholar 

  • Haslett C, Savill JS, Meagher L (1989) The neutrophil. Curr Opin Immunol 2:10–18

    Article  PubMed  CAS  Google Scholar 

  • Hrdlickova B, Holla LI (2011) Relationship between the 17q21 locus and adult asthma in a Czech population. Hum Immunol 72:921–925. doi:10.1016/j.humimm.2011.07.309

    Article  PubMed  CAS  Google Scholar 

  • Hunninghake GM, Soto-Quiros ME, Avila L, Kim HP, Lasky-Su J, Rafaels N, Ruczinski I, Beaty TH, Mathias RA, Barnes KC, Wilk JB, O’Connor GT, Gauderman WJ, Vora H, Baurley JW, Gilliland F, Liang C, Sylvia JS, Klanderman BJ, Sharma SS, Himes BE, Bossley CJ, Israel E, Raby BA, Bush A, Choi AM, Weiss ST, Celedon JC (2010) TSLP polymorphisms are associated with asthma in a sex-specific fashion. Allergy 65:1566–1575. doi:10.1111/j.1398-9995.2010.02415.x

    Article  PubMed  Google Scholar 

  • Kabesch M, Michel S, Tost J (2010) Epigenetic mechanisms and the relationship to childhood asthma. Eur Respir J 36:950–961

    Article  PubMed  CAS  Google Scholar 

  • Karmaus W, Ziyab AH, Everson T, Holloway JW (2013) Epigenetic mechanisms and models in the origins of asthma. Curr Opin Allergy Clin Immunol 13:63–69. doi:10.1097/ACI.0b013e32835ad0e7

    Article  PubMed  Google Scholar 

  • Kynyk JA, Mastronarde JG, McCallister JW (2010) Asthma, the sex difference. Curr Opin Pulm Med 17:6–11. doi:10.1097/MCP.0b013e3283410038

    Article  Google Scholar 

  • Loisel DA, Tan Z, Tisler CJ, Evans MD, Gangnon RE, Jackson DJ, Gern JE, Lemanske RF Jr, Ober C (2011) IFNG genotype and sex interact to influence the risk of childhood asthma. J Allergy Clin Immunol 128:524–531. doi:10.1016/j.jaci.2011.06.016

    Article  PubMed  CAS  Google Scholar 

  • Madore AM, Tremblay K, Hudson TJ, Laprise C (2008) Replication of an association between 17q21 SNPs and asthma in a French–Canadian familial collection. Hum Genet 123:93–95

    Article  PubMed  CAS  Google Scholar 

  • McCallister JW, Mastronarde JG (2008) Sex differences in asthma. J Asthma 45:853–861

    Article  PubMed  Google Scholar 

  • Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, Depner M, von Berg A, Bufe A, Rietschel E, Heinzmann A, Simma B, Frischer T, Willis-Owen SA, Wong KC, Illig T, Vogelberg C, Weiland SK, von Mutius E, Abecasis GR, Farrall M, Gut IG, Lathrop GM, Cookson WO (2007) Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448:470–473

    Article  PubMed  CAS  Google Scholar 

  • Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO (2010) A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 363:1211–1221

    Article  PubMed  CAS  Google Scholar 

  • Morales E, Bustamante M, Vilahur N, Escaramis G, Montfort M, de Cid R, Garcia-Esteban R, Torrent M, Estivill X, Grimalt JO, Sunyer J (2012) DNA hypomethylation at ALOX12 is associated with persistent wheezing in childhood. Am J Respir Crit Care Med. doi:10.1164/rccm.201105-0870OC

    Google Scholar 

  • Morgan HD, Sutherland HG, Martin DI, Whitelaw E (1999) Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23:314–318

    Article  PubMed  CAS  Google Scholar 

  • Munthe-Kaas MC, Bertelsen RJ, Torjussen TM, Hjorthaug HS, Undlien DE, Lyle R, Gervin K, Granum B, Mowinckel P, Carlsen KH, Carlsen KC (2012) Pet keeping and tobacco exposure influence CD14 methylation in childhood. Pediatr Allergy Immunol 23:747–754. doi:10.1111/pai.12021

    Article  PubMed  Google Scholar 

  • Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, Tager I (2010) Ambient air pollution impairs regulatory T-cell function in asthma. J Allergy Clin Immunol 126:845–852 e10

    Article  PubMed  CAS  Google Scholar 

  • Nalls MA, Couper DJ, Tanaka T, van Rooij FJ, Chen MH, Smith AV, Toniolo D, Zakai NA, Yang Q, Greinacher A, Wood AR, Garcia M, Gasparini P, Liu Y, Lumley T, Folsom AR, Reiner AP, Gieger C, Lagou V, Felix JF, Volzke H, Gouskova NA, Biffi A, Doring A, Volker U, Chong S, Wiggins KL, Rendon A, Dehghan A, Moore M, Taylor K, Wilson JG, Lettre G, Hofman A, Bis JC, Pirastu N, Fox CS, Meisinger C, Sambrook J, Arepalli S, Nauck M, Prokisch H, Stephens J, Glazer NL, Cupples LA, Okada Y, Takahashi A, Kamatani Y, Matsuda K, Tsunoda T, Kubo M, Nakamura Y, Yamamoto K, Kamatani N, Stumvoll M, Tonjes A, Prokopenko I, Illig T, Patel KV, Garner SF, Kuhnel B, Mangino M, Oostra BA, Thein SL, Coresh J, Wichmann HE, Menzel S, Lin J, Pistis G, Uitterlinden AG, Spector TD, Teumer A, Eiriksdottir G, Gudnason V, Bandinelli S, Frayling TM, Chakravarti A, van Duijn CM, Melzer D, Ouwehand WH, Levy D, Boerwinkle E, Singleton AB, Hernandez DG, Longo DL, Soranzo N, Witteman JC, Psaty BM, Ferrucci L, Harris TB, O’Donnell CJ, Ganesh SK (2011) Multiple Loci are associated with white blood cell phenotypes. PLoS Genet 7:e1002113. doi:10.1371/journal.pgen.1002113

    Article  PubMed  CAS  Google Scholar 

  • Nyholt DR (2004) A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 74:765–769. doi:10.1086/383251

    Article  PubMed  CAS  Google Scholar 

  • Oates NA, van Vliet J, Duffy DL, Kroes HY, Martin NG, Boomsma DI, Campbell M, Coulthard MG, Whitelaw E, Chong S (2006) Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly. Am J Hum Genet 79:155–162. doi:10.1086/505031

    Article  PubMed  CAS  Google Scholar 

  • Okada Y, Kamatani Y, Takahashi A, Matsuda K, Hosono N, Ohmiya H, Daigo Y, Yamamoto K, Kubo M, Nakamura Y, Kamatani N (2010) Common variations in PSMD3-CSF3 and PLCB4 are associated with neutrophil count. Hum Mol Genet 19:2079–2085. doi:10.1093/hmg/ddq080

    Article  PubMed  CAS  Google Scholar 

  • Pascual M, Suzuki M, Isidoro-Garcia M, Padron J, Turner T, Lorente F, Davila I, Greally JM (2011) Epigenetic changes in B lymphocytes associated with house dust mite allergic asthma. Epigenetics 6:1131–1137. doi:10.4161/epi.6.9.16061

    Google Scholar 

  • Perera F, Tang WY, Herbstman J, Tang D, Levin L, Miller R, Ho SM (2009) Relation of DNA methylation of 5′-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS ONE 4:e4488. doi:10.1371/journal.pone.0004488

    Article  PubMed  Google Scholar 

  • Reiner AP, Lettre G, Nalls MA, Ganesh SK, Mathias R, Austin MA, Dean E, Arepalli S, Britton A, Chen Z, Couper D, Curb JD, Eaton CB, Fornage M, Grant SF, Harris TB, Hernandez D, Kamatini N, Keating BJ, Kubo M, LaCroix A, Lange LA, Liu S, Lohman K, Meng Y, Mohler ER 3rd, Musani S, Nakamura Y, O’Donnell CJ, Okada Y, Palmer CD, Papanicolaou GJ, Patel KV, Singleton AB, Takahashi A, Tang H, Taylor HA Jr, Taylor K, Thomson C, Yanek LR, Yang L, Ziv E, Zonderman AB, Folsom AR, Evans MK, Liu Y, Becker DM, Snively BM, Wilson JG (2011) Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT). PLoS Genet 7:e1002108. doi:10.1371/journal.pgen.1002108

    Article  PubMed  CAS  Google Scholar 

  • Sawalha AH, Wang L, Nadig A, Somers EC, McCune WJ, Hughes T, Merrill JT, Scofield RH, Strickland FM, Richardson B (2012) Sex-specific differences in the relationship between genetic susceptibility, T cell DNA demethylation and lupus flare severity. J Autoimmun 38:J216–J222. doi:10.1016/j.jaut.2011.11.008

    Article  PubMed  CAS  Google Scholar 

  • Smit LA, Bouzigon E, Pin I, Siroux V, Monier F, Aschard H, Bousquet J, Gormand F, Just J, Le Moual N, Nadif R, Scheinmann P, Vervloet D, Lathrop M, Demenais F, Kauffmann F (2009) 17q21 variants modify the association between early respiratory infections and asthma. Eur Respir J 36:57–64

    Article  PubMed  Google Scholar 

  • Sood A, Petersen H, Blanchette CM, Meek P, Picchi MA, Belinsky SA, Tesfaigzi Y (2012) Methylated Genes in Sputum among Older Smokers with Asthma. Chest. doi:10.1378/chest.11-2519

    PubMed  Google Scholar 

  • Soranzo N, Spector TD, Mangino M, Kuhnel B, Rendon A, Teumer A, Willenborg C, Wright B, Chen L, Li M, Salo P, Voight BF, Burns P, Laskowski RA, Xue Y, Menzel S, Altshuler D, Bradley JR, Bumpstead S, Burnett MS, Devaney J, Doring A, Elosua R, Epstein SE, Erber W, Falchi M, Garner SF, Ghori MJ, Goodall AH, Gwilliam R, Hakonarson HH, Hall AS, Hammond N, Hengstenberg C, Illig T, Konig IR, Knouff CW, McPherson R, Melander O, Mooser V, Nauck M, Nieminen MS, O’Donnell CJ, Peltonen L, Potter SC, Prokisch H, Rader DJ, Rice CM, Roberts R, Salomaa V, Sambrook J, Schreiber S, Schunkert H, Schwartz SM, Serbanovic-Canic J, Sinisalo J, Siscovick DS, Stark K, Surakka I, Stephens J, Thompson JR, Volker U, Volzke H, Watkins NA, Wells GA, Wichmann HE, Van Heel DA, Tyler-Smith C, Thein SL, Kathiresan S, Perola M, Reilly MP, Stewart AF, Erdmann J, Samani NJ, Meisinger C, Greinacher A, Deloukas P, Ouwehand WH, Gieger C (2009) A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet 41:1182–1190. doi:10.1038/ng.467

    Article  PubMed  CAS  Google Scholar 

  • Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, Himes BE, Levin AM, Mathias RA, Hancock DB, Baurley JW, Eng C, Stern DA, Celedon JC, Rafaels N, Capurso D, Conti DV, Roth LA, Soto-Quiros M, Togias A, Li X, Myers RA, Romieu I, Van Den Berg DJ, Hu D, Hansel NN, Hernandez RD, Israel E, Salam MT, Galanter J, Avila PC, Avila L, Rodriquez-Santana JR, Chapela R, Rodriguez-Cintron W, Diette GB, Adkinson NF, Abel RA, Ross KD, Shi M, Faruque MU, Dunston GM, Watson HR, Mantese VJ, Ezurum SC, Liang L, Ruczinski I, Ford JG, Huntsman S, Chung KF, Vora H, Calhoun WJ, Castro M, Sienra-Monge JJ, del Rio-Navarro B, Deichmann KA, Heinzmann A, Wenzel SE, Busse WW, Gern JE, Lemanske RF Jr, Beaty TH, Bleecker ER, Raby BA, Meyers DA, London SJ, Gilliland FD, Burchard EG, Martinez FD, Weiss ST, Williams LK, Barnes KC, Ober C, Nicolae DL (2011) Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 43:887–892. doi:10.1038/ng.888

    Article  PubMed  CAS  Google Scholar 

  • Torrone D, Kuriakose J, Moors K, Jiang H, Niedzwiecki M, Perera F, Miller R (2012) Reproducibility and intraindividual variation over days in buccal cell DNA methylation of two asthma genes, interferon gamma (IFNgamma) and inducible nitric oxide synthase (iNOS). Clin Epigenetics 4:3. doi:10.1186/1868-7083-4-3

    Article  PubMed  CAS  Google Scholar 

  • van der Valk RJ, Duijts L, Kerkhof M, Willemsen SP, Hofman A, Moll HA, Smit HA, Brunekreef B, Postma DS, Jaddoe VW, Koppelman GH, de Jongste JC (2012) Interaction of a 17q12 variant with both fetal and infant smoke exposure in the development of childhood asthma-like symptoms: epidemiology and genetics. Allergy. doi:10.1111/j.1398-9995.2012.02819.x

    Google Scholar 

  • Verlaan DJ, Berlivet S, Hunninghake GM, Madore AM, Lariviere M, Moussette S, Grundberg E, Kwan T, Ouimet M, Ge B, Hoberman R, Swiatek M, Dias J, Lam KC, Koka V, Harmsen E, Soto-Quiros M, Avila L, Celedon JC, Weiss ST, Dewar K, Sinnett D, Laprise C, Raby BA, Pastinen T, Naumova AK (2009a) Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease. Am J Hum Genet 85:377–393

    Article  PubMed  CAS  Google Scholar 

  • Verlaan DJ, Ge B, Grundberg E, Hoberman R, Lam KC, Koka V, Dias J, Gurd S, Martin NW, Mallmin H, Nilsson O, Harmsen E, Dewar K, Kwan T, Pastinen T (2009b) Targeted screening of cis-regulatory variation in human haplotypes. Genome Res 19:118–127

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors want to thank the families for their valuable participation. The work was supported by funds from the Canadian Institutes for Health Research (A.N. and C.L.). C.L. holds the Canada Research Chair on Genetic Determinants in Asthma; is the director of the Asthma Inflammation and Remodeling Strategic Group of the Respiratory Health Network of the FRQS and is a member of AllerGen NCE. A.A. is a recipient of the National Guard Health Affairs Saudi Arabia scholarship. The authors are grateful to Jacky Leung for technical assistance and Dr. Luigi Bouchard for the equipment sharing and technical support.

Web Resources

UCSC Genome Bioinformatics/UCSC Genome Browser http://genome.ucsc.edu/

National Human Genome Research Institute http://www.genome.gov

BiQ Analyzer software (Max-Planck-Institute for Informatics, Saarbrücken, Germany) http://biq-analyzer.bioinf.mpi-inf.mpg.de

Quantification tool for methylation analysis (RIKEN Center for Developmental Biology, Kobe, Japan) http://quma.cdb.riken.jp

Simple Interactive Statistical Analysis http://www.quantitativeskills.com/sisa/about/instr.htm.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, McGill University, Montreal, QC, H3A 1A1, Canada

    Anna K. Naumova & Soizik Berlivet

  2. Department of Human Genetics, McGill University, Montreal, QC, H3A 1B1, Canada

    Anna K. Naumova & Abeer Al Tuwaijri

  3. The Research Institute of the McGill University Health Care Centre, Montreal, QC, H3H 2R9, Canada

    Anna K. Naumova, Hamid-Reza Kohan-Ghadr & Sanny Moussette

  4. Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Chicoutimi, QC, G7H 2B1, Canada

    Andréanne Morin, Vanessa T. Vaillancout, Anne-Marie Madore & Catherine Laprise

Authors
  1. Anna K. Naumova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abeer Al Tuwaijri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andréanne Morin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vanessa T. Vaillancout
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne-Marie Madore
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Soizik Berlivet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hamid-Reza Kohan-Ghadr
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sanny Moussette
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Catherine Laprise
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna K. Naumova.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 455 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naumova, A.K., Al Tuwaijri, A., Morin, A. et al. Sex- and age-dependent DNA methylation at the 17q12-q21 locus associated with childhood asthma. Hum Genet 132, 811–822 (2013). https://doi.org/10.1007/s00439-013-1298-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-013-1298-z

Keywords

Search

Navigation