406
Views
0
CrossRef citations to date
0
Altmetric
Review

Genetic and Environmental Impacts on DNA Methylation Levels in Twins

, , , &
Pages 105-117 | Received 01 Jun 2015, Accepted 10 Sep 2015, Published online: 18 Dec 2015

References

  • Bell JT , SpectorTD . A twin approach to unraveling epigenetics . Trends Genet.27 ( 3 ), 116 – 125 ( 2011 ).
  • Holliday R . Epigenetics: an overview . Dev. Genet.15 ( 6 ), 453 – 457 ( 1994 ).
  • Richards EJ . Inherited epigenetic variation – revisiting soft inheritance . Nat. Rev. Genet.7 ( 5 ), 395 – 401 ( 2006 ).
  • Holliday R , PughJE . DNA modification mechanisms and gene activity during development . Science187 ( 4173 ), 226 – 232 ( 1975 ).
  • Cosgrove MS , WolbergerC . How does the histone code work?Biochem. Cell Biol.83 ( 4 ), 468 – 476 ( 2005 ).
  • Venter JC , AdamsMD , MyersEWet al. The sequence of the human genome . Science291 ( 5507 ), 1304 – 1351 ( 2001 ).
  • Lander ES , LintonLM , BirrenBet al. Initial sequencing and analysis of the human genome . Nature409 ( 6822 ), 860 – 921 ( 2001 ).
  • Antequera F , BirdA . Number of CpG islands and genes in human and mouse . Proc. Natl Acad. Sci. USA90 ( 24 ), 11995 – 11999 ( 1993 ).
  • Larsen F , GundersenG , LopezR , PrydzH . CpG islands as gene markers in the human genome . Genomics13 ( 4 ), 1095 – 1107 ( 1992 ).
  • Doi A , ParkIH , WenBet al. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts . Nat. Genet.41 ( 12 ), 1350 – 1353 ( 2009 ).
  • Irizarry RA , Ladd-AcostaC , WenBet al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores . Nat. Genet.41 ( 2 ), 178 – 186 ( 2009 ).
  • Bird A . DNA methylation patterns and epigenetic memory . Genes Dev.16 ( 1 ), 6 – 21 ( 2002 ).
  • Li E , BestorTH , JaenischR . Targeted mutation of the DNA methyltransferase gene results in embryonic lethality . Cell69 ( 6 ), 915 – 926 ( 1992 ).
  • Reik W . Stability and flexibility of epigenetic gene regulation in mammalian development . Nature447 ( 7143 ), 425 – 432 ( 2007 ).
  • Ball MP , LiJB , GaoYet al. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells . Nat. Biotechnol.27 ( 4 ), 361 – 368 ( 2009 ).
  • Gutierrez-Arcelus M , LappalainenT , MontgomerySBet al. Passive and active DNA methylation and the interplay with genetic variation in gene regulation . Elife2 , e00523 ( 2013 ).
  • Cassidy SB , DykensE , WilliamsCA . Prader–Willi and Angelman syndromes: sister imprinted disorders . Am. J. Med. Genet.97 ( 2 ), 136 – 146 ( 2000 ).
  • Laird PW . Principles and challenges of genomewide DNA methylation analysis . Nat. Rev. Genet.11 ( 3 ), 191 – 203 ( 2010 ).
  • Bibikova M , LeJ , BarnesBet al. Genome-wide DNA methylation profiling using Infinium® assay . Epigenomics1 ( 1 ), 177 – 200 ( 2009 ).
  • Steemers FJ , GundersonKL . Whole genome genotyping technologies on the BeadArray platform . Biotechnol. J.2 ( 1 ), 41 – 49 ( 2007 ).
  • Cokus SJ , FengS , ZhangXet al. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning . Nature452 ( 7184 ), 215 – 219 ( 2008 ).
  • Lister R , O’MalleyRC , Tonti-FilippiniJet al. Highly integrated single-base resolution maps of the epigenome in Arabidopsis . Cell133 ( 3 ), 523 – 536 ( 2008 ).
  • Lister R , PelizzolaM , DowenRHet al. Human DNA methylomes at base resolution show widespread epigenomic differences . Nature462 ( 7271 ), 315 – 322 ( 2009 ).
  • Meissner A , MikkelsenTS , GuHet al. Genome-scale DNA methylation maps of pluripotent and differentiated cells . Nature454 ( 7205 ), 766 – 770 ( 2008 ).
  • Weber M , DaviesJJ , WittigDet al. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells . Nat. Genet.37 ( 8 ), 853 – 862 ( 2005 ).
  • Weber M , HellmannI , StadlerMBet al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome . Nat. Genet.39 ( 4 ), 457 – 466 ( 2007 ).
  • Strachan T , ReadAP , StrachanT . Human Molecular Genetics . Garland Science , New York, USA ( 2011 ).
  • Boomsma D , BusjahnA , PeltonenL . Classical twin studies and beyond . Nat. Rev. Genet.3 ( 11 ), 872 – 882 ( 2002 ).
  • Neale MC , CardonLR . North Atlantic Treaty Organization, Scientific Affairs Division . Methodology for Genetic Studies of Twins and Families . Kluwer Academic Publishers , Dordrecht, Boston, USA ( 1992 ).
  • MacGregor AJ , SniederH , SchorkNJ , SpectorTD . Twins. Novel uses to study complex traits and genetic diseases . Trends Genet.16 ( 3 ), 131 – 134 ( 2000 ).
  • Visscher PM , PosthumaD . Statistical power to detect genetic Loci affecting environmental sensitivity . Behav. Genet.40 ( 5 ), 728 – 733 ( 2010 ).
  • Reik W , DeanW , WalterJ . Epigenetic reprogramming in mammalian development . Science293 ( 5532 ), 1089 – 1093 ( 2001 ).
  • Bjornsson HT , SigurdssonMI , FallinMDet al. Intra-individual change over time in DNA methylation with familial clustering . JAMA299 ( 24 ), 2877 – 2883 ( 2008 ).
  • Mcrae AF , PowellJE , HendersAKet al. Contribution of genetic variation to transgenerational inheritance of DNA methylation . Genome Biol.15 ( 5 ), R73 ( 2014 ).
  • Bell JT , SafferyR . The value of twins in epigenetic epidemiology . Int. J. Epidemiol.41 ( 1 ), 140 – 150 ( 2012 ).
  • Javierre BM , FernandezAF , RichterJet al. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus . Genome Res.20 ( 2 ), 170 – 179 ( 2010 ).
  • Kuratomi G , IwamotoK , BundoMet al. Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins . Mol. Psychiat.13 ( 4 ), 429 – 441 ( 2008 ).
  • Gervin K , Hammer⊘M , AkselsenHEet al. Extensive variation and low heritability of DNA methylation identified in a twin study . Genome Res.21 ( 11 ), 1813 – 1821 ( 2011 ).
  • Gordon L , JooJE , PowellJEet al. Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence . Genome Res.22 ( 8 ), 1395 – 1406 ( 2012 ).
  • Grundberg E , MeduriE , SandlingJKet al. Global analysis of DNA methylation variation in adipose tissue from twins reveals links to disease-associated variants in distal regulatory elements . Am. J. Hum. Genet.93 ( 5 ), 876 – 890 ( 2013 ).
  • Bell JT , TsaiPC , YangTPet al. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population . PLoS Genet.8 ( 4 ), e1002629 ( 2012 ).
  • Heijmans BT , KremerD , TobiEW , BoomsmaDI , SlagboomPE . Heritable rather than age-related environmental and stochastic factors dominate variation in DNA methylation of the human IGF2/H19 locus . Hum. Mol. Genet.16 ( 5 ), 547 – 554 ( 2007 ).
  • Wong CC , CaspiA , WilliamsBet al. A longitudinal study of epigenetic variation in twins . Epigenetics5 ( 6 ), 516 – 526 ( 2010 ).
  • Kaminsky ZA , TangT , WangSCet al. DNA methylation profiles in monozygotic and dizygotic twins . Nat. Genet.41 ( 2 ), 240 – 245 ( 2009 ).
  • Bell JT , PaiAA , PickrellJKet al. DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines . Genome Biol.12 ( 1 ), R10 ( 2011 ).
  • Zhang D , ChengL , BadnerJAet al. Genetic control of individual differences in gene-specific methylation in human brain . Am. J. Hum. Genet.86 ( 3 ), 411 – 419 ( 2010 ).
  • Gibbs JR , Van Der BrugMP , HernandezDGet al. Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain . PLoS Genet.6 ( 5 ), e1000952 ( 2010 ).
  • Drong AW , NicholsonG , HedmanAKet al. The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue . PLoS ONE8 ( 2 ), e55923 ( 2013 ).
  • Van Eijk KR , De JongS , BoksMPet al. Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects . BMC Genomics13 , 636 ( 2012 ).
  • Gamazon ER , BadnerJA , ChengLet al. Enrichment of cis-regulatory gene expression SNPs and methylation quantitative trait loci among bipolar disorder susceptibility variants . Mol. Psychiat.18 ( 3 ), 340 – 346 ( 2013 ).
  • Shi J , MarconettCN , DuanJet al. Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue . Nat. Commun.5 , 3365 ( 2014 ).
  • Banovich NE , LanX , McvickerGet al. Methylation QTLs are associated with coordinated changes in transcription factor binding, histone modifications, and gene expression levels . PLoS Genet.10 ( 9 ), e1004663 ( 2014 ).
  • Smith AK , KilaruV , KocakMet al. Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type . BMC Genomics15 , 145 ( 2014 ).
  • Wagner JR , BuscheS , GeB , KwanT , PastinenT , BlanchetteM . The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts . Genome Biol.15 ( 2 ), R37 ( 2014 ).
  • Fraser HB , LamLL , NeumannSM , KoborMS . Population-specificity of human DNA methylation . Genome Biol.13 ( 2 ), R8 ( 2012 ).
  • Stadler MB , MurrR , BurgerLet al. DNA-binding factors shape the mouse methylome at distal regulatory regions . Nature480 ( 7378 ), 490 – 495 ( 2011 ).
  • Lienert F , WirbelauerC , SomI , DeanA , MohnF , SchübelerD . Identification of genetic elements that autonomously determine DNA methylation states . Nat. Genet.43 ( 11 ), 1091 – 1097 ( 2011 ).
  • Consortium EP . A user’s guide to the encyclopedia of DNA elements (ENCODE) . PLoS Biol.9 ( 4 ), e1001046 ( 2011 ).
  • Ziller MJ , GuH , MüllerFet al. Charting a dynamic DNA methylation landscape of the human genome . Nature500 ( 7463 ), 477 – 481 ( 2013 ).
  • Shukla S , KavakE , GregoryMet al. CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing . Nature479 ( 7371 ), 74 – 79 ( 2011 ).
  • Gutierrez-Arcelus M , OngenH , LappalainenTet al. Tissue-specific effects of genetic and epigenetic variation on gene regulation and splicing . PLoS Genet.11 ( 1 ), e1004958 ( 2015 ).
  • Sadovnick AD , ArmstrongH , RiceGPet al. A population-based study of multiple sclerosis in twins: update . Ann. Neurol.33 ( 3 ), 281 – 285 ( 1993 ).
  • Cardno AG , GottesmanII . Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics . Am. J. Med. Genet.97 ( 1 ), 12 – 17 ( 2000 ).
  • Bell JT , SpectorTD . DNA methylation studies using twins: what are they telling us?Genome Biol.13 ( 10 ), 172 ( 2012 ).
  • Bruder CE , PiotrowskiA , GijsbersAAet al. Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles . Am. J. Hum. Genet.82 ( 3 ), 763 – 771 ( 2008 ).
  • Breckpot J , ThienpontB , GewilligM , AllegaertK , VermeeschJR , DevriendtK . Differences in copy number variation between discordant monozygotic twins as a model for exploring chromosomal mosaicism in congenital heart defects . Mol. Syndromol.2 ( 2 ), 81 – 87 ( 2012 ).
  • Maiti S , KumarKH , CastellaniCA , O’ReillyR , SinghSM . Ontogenetic de novo copy number variations (CNVs) as a source of genetic individuality: studies on two families with MZD twins for schizophrenia . PLoS ONE6 ( 3 ), e17125 ( 2011 ).
  • Bouhlal Y , MartinezS , GongH , DumasK , ShiehJT . Twin mitochondrial sequence analysis . Mol. Genet. Genomic Med.1 ( 3 ), 174 – 186 ( 2013 ).
  • Tsuang MT , BarJL , StoneWS , FaraoneSV . Gene-environment interactions in mental disorders . World Psychiatry3 ( 2 ), 73 – 83 ( 2004 ).
  • Fraga MF , BallestarE , PazMFet al. Epigenetic differences arise during the lifetime of monozygotic twins . Proc. Natl Acad. Sci. USA102 ( 30 ), 10604 – 10609 ( 2005 ).
  • Ollikainen M , SmithKR , JooEJet al. DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome . Hum. Mol. Genet.19 ( 21 ), 4176 – 4188 ( 2010 ).
  • Szyf M . DNA methylation, behavior and early life adversity . J. Genet. Genomics.40 ( 7 ), 331 – 338 ( 2013 ).
  • Jaenisch R , BirdA . Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals . Nat. Genet.33 ( Suppl ), 245 – 254 ( 2003 ).
  • Weaver IC , CervoniN , ChampagneFAet al. Epigenetic programming by maternal behavior . Nat. Neurosci.7 ( 8 ), 847 – 854 ( 2004 ).
  • Shenker NS , PolidoroS , Van VeldhovenKet al. Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking . Hum. Mol. Genet.22 ( 5 ), 843 – 851 ( 2013 ).
  • Besingi W , JohanssonA . Smoke-related DNA methylation changes in the etiology of human disease . Hum. Mol. Genet.23 ( 9 ), 2290 – 2297 ( 2014 ).
  • Breitling LP , YangR , KornB , BurwinkelB , BrennerH . Tobacco-smoking-related differential DNA methylation: 27K discovery and replication . Am. J. Hum. Genet.88 ( 4 ), 450 – 457 ( 2011 ).
  • Buro-Auriemma LJ , SalitJ , HackettNRet al. Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression . Hum. Mol. Genet.22 ( 23 ), 4726 – 4738 ( 2013 ).
  • Elliott HR , TillinT , McardleWLet al. Differences in smoking associated DNA methylation patterns in south Asians and Europeans . Clin. Epigenetics6 ( 1 ), 4 ( 2014 ).
  • Philibert RA , BeachSR , LeiMK , BrodyGH . Changes in DNA methylation at the aryl hydrocarbon receptor repressor may be a new biomarker for smoking . Clin. Epigenetics5 ( 1 ), 19 ( 2013 ).
  • Shenker NS , UelandPM , PolidoroSet al. DNA methylation as a long-term biomarker of exposure to tobacco smoke . Epidemiology24 ( 5 ), 712 – 716 ( 2013 ).
  • Sun YV , SmithAK , ConneelyKNet al. Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans . Hum. Genet.132 ( 9 ), 1027 – 1037 ( 2013 ).
  • Wan ES , QiuW , BaccarelliAet al. Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome . Hum. Mol. Genet.21 ( 13 ), 3073 – 3082 ( 2012 ).
  • Zeilinger S , KühnelB , KloppNet al. Tobacco smoking leads to extensive genome-wide changes in DNA methylation . PLoS ONE8 ( 5 ), e63812 ( 2013 ).
  • Guida F , SandangerTM , CastagnéRet al. Dynamics of smoking-induced genome-wide methylation changes with time since smoking cessation . Hum. Mol. Genet.24 ( 8 ), 2349 – 2359 ( 2015 ).
  • Harlid S , XuZ , PanduriV , SandlerDP , TaylorJA . CpG sites associated with cigarette smoking: analysis of epigenome-wide data from the Sister Study . Environ. Health Perspect.122 ( 7 ), 673 – 678 ( 2014 ).
  • Dogan MV , ShieldsB , CutronaCet al. The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women . BMC Genomics15 , 151 ( 2014 ).
  • Monick MM , BeachSR , PlumeJet al. Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers . Am. J. Med. Genet. B Neuropsychiatr. Genet.159B ( 2 ), 141 – 151 ( 2012 ).
  • Zhang Y , YangR , BurwinkelB , BreitlingLP , BrennerH . F2RL3 methylation as a biomarker of current and lifetime smoking exposures . Environ. Health Perspect.122 ( 2 ), 131 – 137 ( 2014 ).
  • Nitert MD , DayehT , VolkovPet al. Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with Type 2 diabetes . Diabetes61 ( 12 ), 3322 – 3332 ( 2012 ).
  • Joubert BR , HåbergSE , NilsenRMet al. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy . Environ. Health Perspect.120 ( 10 ), 1425 – 1431 ( 2012 ).
  • Markunas CA , XuZ , HarlidSet al. Identification of DNA methylation changes in newborns related to maternal smoking during pregnancy . Environ. Health Perspect.122 ( 10 ), 1147 – 1153 ( 2014 ).
  • Suter M , MaJ , HarrisAet al. Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression . Epigenetics6 ( 11 ), 1284 – 1294 ( 2011 ).
  • Lee KW , RichmondR , HuPet al. Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age . Environ. Health Perspect.123 ( 2 ), 193 – 199 ( 2015 ).
  • Richmond RC , SimpkinAJ , WoodwardGet al. Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) . Hum. Mol. Genet.24 ( 8 ), 2201 – 2217 ( 2015 ).
  • Ivorra C , FragaMF , BayónGFet al. DNA methylation patterns in newborns exposed to tobacco in utero . J. Transl. Med.13 ( 1 ), 25 ( 2015 ).
  • Breton CV , SiegmundKD , JoubertBRet al. Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation . PLoS ONE9 ( 6 ), e99716 ( 2014 ).
  • Zhang H , HermanAI , KranzlerHRet al. Array-based profiling of DNA methylation changes associated with alcohol dependence . Alcohol. Clin. Exp. Res.37 ( Suppl. 1 ), E108 – E115 ( 2013 ).
  • Philibert RA , PlumeJM , GibbonsFX , BrodyGH , BeachSR . The impact of recent alcohol use on genome wide DNA methylation signatures . Front. Genet.3 , 54 ( 2012 ).
  • Thapar M , CovaultJ , HesselbrockV , BonkovskyHL . DNA methylation patterns in alcoholics and family controls . World J. Gastrointest. Oncol.4 ( 6 ), 138 – 144 ( 2012 ).
  • Zhao R , ZhangR , LiWet al. Genome-wide DNA methylation patterns in discordant sib pairs with alcohol dependence . Asia Pac. Psychiatry5 ( 1 ), 39 – 50 ( 2013 ).
  • Voisin S , AlménMS , MoschonisG , ChrousosGP , ManiosY , SchiöthHB . Dietary fat quality impacts genome-wide DNA methylation patterns in a cross-sectional study of Greek preadolescents . Eur. J. Hum. Genet.23 ( 5 ), 654 – 662 ( 2015 ).
  • Amarasekera M , MartinoD , AshleySet al. Genome-wide DNA methylation profiling identifies a folate-sensitive region of differential methylation upstream of ZFP57-imprinting regulator in humans . FASEB J.28 ( 9 ), 4068 – 4076 ( 2014 ).
  • Dominguez-Salas P , MooreSE , BakerMSet al. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles . Nat. Commun.5 , 3746 ( 2014 ).
  • Rönn T , VolkovP , DavegårdhCet al. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue . PLoS Genet.9 ( 6 ), e1003572 ( 2013 ).
  • Grönniger E , WeberB , HeilOet al. Aging and chronic sun exposure cause distinct epigenetic changes in human skin . PLoS Genet.6 ( 5 ), e1000971 ( 2010 ).
  • Vandiver AR , IrizarryRA , HansenKDet al. Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin . Genome Biol.16 ( 1 ), 80 ( 2015 ).
  • Argos M , ChenL , JasmineFet al. Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh . Environ. Health Perspect.123 ( 1 ), 64 – 71 ( 2015 ).
  • Broberg K , AhmedS , EngströmKet al. Arsenic exposure in early pregnancy alters genome-wide DNA methylation in cord blood, particularly in boys . J. Dev. Orig. Health Dis.5 ( 4 ), 288 – 298 ( 2014 ).
  • Van Dongen J , SlagboomPE , DraismaHH , MartinNG , BoomsmaDI . The continuing value of twin studies in the omics era . Nat. Rev. Genet.13 ( 9 ), 640 – 653 ( 2012 ).
  • Snieder H , WangX , MacGregorAJ . Twin methodology . In : Encyclopedia of Life Sciences (ELS) . John Wiley & Sons , Chichester, UK ( 2010 ).
  • Rakyan VK , DownTA , BaldingDJ , BeckS . Epigenome-wide association studies for common human diseases . Nat. Rev. Genet.12 ( 8 ), 529 – 541 ( 2011 ).
  • Liu Y , AryeeMJ , PadyukovLet al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis . Nat. Biotechnol.31 ( 2 ), 142 – 147 ( 2013 ).
  • Kinoshita M , NumataS , TajimaAet al. DNA methylation signatures of peripheral leukocytes in schizophrenia . Neuromolecular Med.15 ( 1 ), 95 – 101 ( 2013 ).
  • Spector T . Identically Different . Weidenfeld & Nicolson , London, UK ( 2012 ).
  • Dempster EL , PidsleyR , SchalkwykLCet al. Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder . Hum. Mol. Genet.20 ( 24 ), 4786 – 4796 ( 2011 ).
  • Rakyan VK , BeyanH , DownTAet al. Identification of Type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis . PLoS Genet.7 ( 9 ), e1002300 ( 2011 ).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.