{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:39:28Z","timestamp":1790818768950,"version":"4.1.0"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":72,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R03HD092776"],"award-info":[{"award-number":["R03HD092776"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH\/NIAID","award":["R01AI121226"],"award-info":[{"award-number":["R01AI121226"]}]},{"name":"National Asthma Campaign, UK","award":["364"],"award-info":[{"award-number":["364"]}]},{"name":"18-year follow-up by a grant from the National Heart and Blood Institute","award":["R01HL082925"],"award-info":[{"award-number":["R01HL082925"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>STUDY QUESTION<\/jats:title><jats:p>Is the age of onset of pubertal markers related to subsequent changes in DNA methylation (DNAm)?<\/jats:p><\/jats:sec><jats:sec><jats:title>SUMMARY ANSWER<\/jats:title><jats:p>We identified 273 cytosine-phosphate-guanine (CpG) dinucleotides in girls and 67 CpGs in boys that were related to puberty and that were replicable in two other investigations.<\/jats:p><\/jats:sec><jats:sec><jats:title>WHAT IS KNOWN ALREADY<\/jats:title><jats:p>Previously, 457 CpGs (not gender-specific) and 347 (in girls) and 50 (in boys), respectively, were found to be associated with puberty, according to investigations of studies from Denmark (20 girls and 31 boys) and North America (30 girls and 25 boys).<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title><jats:p>The study was based on a birth cohort of 1456 participants born in 1989\/90, with follow-up at age 10 and 18\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title><jats:p>The follow-up included 470 participants with information on DNAm and age of pubertal onset (244 girls and 226 boys). Age of pubertal onset was ascertained retrospectively at age 18\u00a0years. Using the Pubertal Development Scale, both genders were asked about ages of onset of growth spurt, body hair growth and skin changes. Ages at voice deepening and growth of facial hair were inquired from boys; ages at breast development and menarche from girls. Blood samples were collected at 10 and 18\u00a0years of age. DNA was extracted using a standard salting out procedure. The methylation level for each CpG site was assessed using one of two different platforms. DNAm was measured by a ratio of intensities denoted as \u03b2 values for each CpG site. After quality control, 349\u2009455 CpG sites were available for analysis. M values were calculated (log2(\u03b2\/(1\u2212\u03b2)) to approximate a normal distribution, and their levels were adjusted for blood cell proportions. Linear mixed models were applied to test the association between age of pubertal markers and repeated measurement of DNAm at 10 and 18\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title><jats:p>In girls, a total of 63\u2009019 CpGs statistically significantly changed after occurrence of any of the five pubertal events and 13\u2009487 were changed subsequent to all five events: the respective number is boys were 3072 and 301. To further exclude false-positive findings, we investigated which CpGs were replicable in prior studies from Denmark or North America, resulting in 273 replicable CpG in girls and 67 CpGs in boys (236 and 68 genes, respectively). Most identified genes are known to be related to biological processes of puberty; however, genetic polymorphisms of only four of these genes were previously linked to pubertal markers in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title><jats:p>The relative age of pubertal onset to the age of DNAm measurements does not allow causal inference, since DNAm at an earlier age may have affected the pubertal age or pubertal age may have altered later DNAm. This investigation concentrates on autosomes. CpGs on X and Y chromosomes are not included in the current study.<\/jats:p><\/jats:sec><jats:sec><jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title><jats:p>Assessment of biological processes involved in pubertal transitions should include epigenetic information. Differential DNAm related to puberty needs to be investigated to determine whether it can act as an early marker for adult diseases known to be associated with puberty.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title><jats:p>This work was supported by NIH grants R03HD092776 (Epigenetic characterization of pubertal transitions) and R01AI121226. The 10-year follow-up of this study was funded by National Asthma Campaign, UK (Grant No 364), and the 18-year follow-up by a grant from the National Heart and Blood Institute (R01 HL082925). The authors have no conflicts to report.<\/jats:p><\/jats:sec>","DOI":"10.1093\/hropen\/hoaa006","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T12:07:15Z","timestamp":1580126835000},"source":"Crossref","is-referenced-by-count":18,"title":["Age at onset of different pubertal signs in boys and girls and differential DNA methylation at age 10 and 18\u00a0years: an epigenome-wide follow-up study"],"prefix":"10.1093","volume":"2020","author":[{"given":"Su","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Mathematical Science, University of Memphis, Dunn Hall, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Refaey","sequence":"first","affiliation":[{"name":"School of Public Health, University of Memphis, Robison Hall, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Mukherjee","sequence":"first","affiliation":[{"name":"School of Public Health, University of Memphis, Robison Hall, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farnaz","family":"Solatikia","sequence":"first","affiliation":[{"name":"Department of Mathematical Science, University of Memphis, Dunn Hall, Memphis, TN, USA"},{"name":"School of Public Health, University of Memphis, Robison Hall, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"first","affiliation":[{"name":"School of Public Health, University of Memphis, Robison Hall, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S Hasan","family":"Arshad","sequence":"first","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK"},{"name":"The David Hide Asthma and Allergy Research Centre, Newport PO30 5TG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Ewart","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W","family":"Holloway","sequence":"first","affiliation":[{"name":"Human Development & Health, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Public Health, University of Memphis, Robison Hall, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2684-1492","authenticated-orcid":false,"given":"Wilfried","family":"Karmaus","sequence":"first","affiliation":[{"name":"School of Public Health, University of Memphis, Robison Hall, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,12]]},"reference":[{"key":"2020050812275907800_ref1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1093\/hmg\/ddu479","article-title":"Risk of childhood asthma is associated with CpG-site polymorphisms, regional DNA methylation and mRNA levels at the GSDMB\/ORMDL3 locus","volume":"24","author":"Acevedo","year":"2015","journal-title":"Hum Mol Genet"},{"key":"2020050812275907800_ref2","doi-asserted-by":"crossref","first-page":"28657","DOI":"10.1038\/srep28657","article-title":"Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood","volume":"6","author":"Almstrup","year":"2016","journal-title":"Sci Rep"},{"key":"2020050812275907800_ref3","doi-asserted-by":"crossref","DOI":"10.1093\/ije\/dyy023","article-title":"Cohort profile: the Isle Of Wight Whole Population Birth Cohort (IOWBC)","author":"Arshad","year":"2018","journal-title":"Int J Epidemiol"},{"key":"2020050812275907800_ref4","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: a flexible and comprehensive bioconductor package for the analysis of Infinium DNA methylation microarrays","volume":"30","author":"Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"2020050812275907800_ref5","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/humupd\/dmx025","article-title":"Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty","volume":"23","author":"Avendano","year":"2017","journal-title":"Hum Reprod Update"},{"key":"2020050812275907800_ref6","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1097\/GME.0000000000000353","article-title":"Age at menarche and its association with dysglycemia in Korean middle-aged women","volume":"22","author":"Baek","year":"2015","journal-title":"Menopause"},{"key":"2020050812275907800_ref7","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J Roy Stat Soc Ser B Meth"},{"key":"2020050812275907800_ref8","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s13148-018-0581-1","article-title":"Methylome profiling of healthy and central precocious puberty girls","volume":"10","author":"Bessa","year":"2018","journal-title":"Clin Epigenetics"},{"key":"2020050812275907800_ref9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/978-1-59745-522-0_12","article-title":"GoldenGate assay for DNA methylation profiling","volume":"507","author":"Bibikova","year":"2009","journal-title":"Methods Mol Biol"},{"key":"2020050812275907800_ref10","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev.biochem.72.121801.161720","article-title":"Mechanisms of alternative pre-messenger RNA splicing","volume":"72","author":"Black","year":"2003","journal-title":"Annu Rev Biochem"},{"key":"2020050812275907800_ref11","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.adolescence.2005.10.001","article-title":"A comparison of self-reported puberty using the Pubertal Development Scale and the Sexual Maturation Scale in a school-based epidemiologic survey","volume":"29","author":"Bond","year":"2006","journal-title":"J Adolesc"},{"key":"2020050812275907800_ref12","doi-asserted-by":"crossref","first-page":"829","DOI":"10.2307\/1130220","article-title":"Validity of self-report measures of girls\u2019 pubertal status","volume":"58","author":"Brooks-Gunn","year":"1987","journal-title":"Child Dev"},{"key":"2020050812275907800_ref13","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/1054-139X(93)90004-9","article-title":"A self-administered rating scale for pubertal development","volume":"14","author":"Carskadon","year":"1993","journal-title":"J Adolesc Health"},{"key":"2020050812275907800_ref14","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1016\/j.orcp.2015.10.003","article-title":"Age at menarche and its association with the metabolic syndrome in Taiwan","volume":"10","author":"Chang","year":"2016","journal-title":"Obes Res Clin Pract"},{"key":"2020050812275907800_ref15","doi-asserted-by":"crossref","first-page":"W305","DOI":"10.1093\/nar\/gkp427","article-title":"ToppGene Suite for gene list enrichment analysis and candidate gene prioritization","volume":"37","author":"Chen","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2020050812275907800_ref16","doi-asserted-by":"crossref","first-page":"18347","DOI":"10.1074\/jbc.R110.205286","article-title":"DNA methylation and demethylation in mammals","volume":"286","author":"Chen","year":"2011","journal-title":"J Biol Chem"},{"key":"2020050812275907800_ref17","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.1093\/hmg\/ddu150","article-title":"Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty","volume":"23","author":"Cousminer","year":"2014","journal-title":"Hum Mol Genet"},{"key":"2020050812275907800_ref18","doi-asserted-by":"crossref","first-page":"srep11208","DOI":"10.1038\/srep11208","article-title":"Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study","volume":"5","author":"Day","year":"2015","journal-title":"Sci Rep-Uk"},{"key":"2020050812275907800_ref19","first-page":"442","article-title":"Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls","volume":"75","author":"de Ridder","year":"1992","journal-title":"J Clin Endocrinol Metab"},{"key":"2020050812275907800_ref20","doi-asserted-by":"crossref","first-page":"771","DOI":"10.2217\/epi.11.105","article-title":"Evaluation of the Infinium Methylation 450K technology","volume":"3","author":"Dedeurwaerder","year":"2011","journal-title":"Epigenomics"},{"key":"2020050812275907800_ref21","doi-asserted-by":"crossref","first-page":"e79391","DOI":"10.1371\/journal.pone.0079391","article-title":"Methylome analysis and epigenetic changes associated with menarcheal age","volume":"8","author":"Demetriou","year":"2013","journal-title":"PLoS One"},{"key":"2020050812275907800_ref22","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1111\/j.1532-7795.2010.00722.x","article-title":"Puberty and its measurement: a decade in review","volume":"21","author":"Dorn","year":"2011","journal-title":"J Res Adolescence"},{"key":"2020050812275907800_ref23","doi-asserted-by":"crossref","first-page":"5345","DOI":"10.1113\/jphysiol.2011.221630","article-title":"Sex specific association of potassium channel subunits","volume":"589","author":"Duffey","year":"2011","journal-title":"J Physiol"},{"key":"2020050812275907800_ref24","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/ng.714","article-title":"Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies","volume":"42","author":"Elks","year":"2010","journal-title":"Nat Genet"},{"key":"2020050812275907800_ref25","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1080\/15592294.2015.1061174","article-title":"Epigenetic landscape correlates with genetic subtype but does not predict outcome in childhood acute lymphoblastic leukemia","volume":"10","author":"Gabriel","year":"2015","journal-title":"Epigenetics"},{"key":"2020050812275907800_ref26","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.jpag.2016.02.011","article-title":"Age at menarche and its association with excess weight and body fat percentage in girls in the southwestern region of the Brazilian Amazon","volume":"29","author":"Gemelli","year":"2016","journal-title":"J Pediatr Adol Gynec"},{"key":"2020050812275907800_ref27","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.4161\/epi.26265","article-title":"Epigenome-wide profiling identifies significant differences in DNA methylation between matched-pairs of T- and B-lymphocytes from healthy individuals","volume":"8","author":"Glossop","year":"2013","journal-title":"Epigenetics"},{"key":"2020050812275907800_ref28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.diabres.2014.10.009","article-title":"Early age at menarche: a risk factor for overweight or obesity in patients with type 1 diabetes living in urban areas?","volume":"107","author":"Gomes","year":"2015","journal-title":"Diabetes Res Clin Pr"},{"key":"2020050812275907800_ref29","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1017\/S0954579409000054","article-title":"Developmental changes in hypothalamus-pituitary-adrenal activity over the transition to adolescence: normative changes and associations with puberty","volume":"21","author":"Gunnar","year":"2009","journal-title":"Dev Psychopathol"},{"key":"2020050812275907800_ref30","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/sj.ijo.0800531","article-title":"Age- and maturity-related changes in body composition during adolescence into adulthood: the Fels Longitudinal Study","volume":"21","author":"Guo","year":"1997","journal-title":"Int J Obes Relat Metab Disord"},{"key":"2020050812275907800_ref31","doi-asserted-by":"crossref","first-page":"6412","DOI":"10.1038\/srep06412","article-title":"Pubertal onset in girls is strongly influenced by genetic variation affecting FSH action","volume":"4","author":"Hagen","year":"2014","journal-title":"Sci Rep"},{"key":"2020050812275907800_ref32","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1186\/s13059-014-0522-z","article-title":"Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets","volume":"15","author":"Hall","year":"2014","journal-title":"Genome Biol"},{"key":"2020050812275907800_ref33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/01.hjh.0000198033.14848.93","article-title":"Age at puberty and adult blood pressure and body size in a British birth cohort study","volume":"24","author":"Hardy","year":"2006","journal-title":"J Hypertens"},{"key":"2020050812275907800_ref34","doi-asserted-by":"crossref","DOI":"10.1186\/s12889-017-4681-1","article-title":"The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study","volume":"17","author":"He","year":"2017","journal-title":"BMC Public Health"},{"key":"2020050812275907800_ref35","doi-asserted-by":"crossref","first-page":"S88","DOI":"10.1002\/gepi.20478","article-title":"Population stratification and patterns of linkage disequilibrium","volume":"33","author":"Hinrichs","year":"2009","journal-title":"Genet Epidemiol"},{"key":"2020050812275907800_ref88","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/1471-2105-13-86","article-title":"DNA methylation arrays as surrogate measures of cell mixture distribution","volume":"13","author":"Houseman","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"2020050812275907800_ref36","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/ijc.2910460508","article-title":"Age at menarche, age at menopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case-control study","volume":"46","author":"Hsieh","year":"1990","journal-title":"Int J Cancer"},{"key":"2020050812275907800_ref37","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1677\/jme.1.01601","article-title":"Gene regulation by NMDA receptor activation in the SDN-POA neurons of male rats during sexual development","volume":"34","author":"Hsu","year":"2005","journal-title":"J Mol Endocrinol"},{"key":"2020050812275907800_ref38","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1093\/aje\/kwm237","article-title":"Association of low age at menarche with increased all-cause mortality: a 37-year follow-up of 61,319 Norwegian women","volume":"166","author":"Jacobsen","year":"2007","journal-title":"Am J Epidemiol"},{"key":"2020050812275907800_ref39","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/ije\/dyn251","article-title":"Age at menarche, total mortality and mortality from ischaemic heart disease and stroke: the Adventist Health Study, 1976\u201388","volume":"38","author":"Jacobsen","year":"2009","journal-title":"Int J Epidemiol"},{"key":"2020050812275907800_ref87","doi-asserted-by":"crossref","first-page":"R31","DOI":"10.1186\/gb-2014-15-2-r31","article-title":"Accounting for cellular heterogeneity is critical in epigenome-wide association studies","volume":"15","author":"Jaffe","year":"2014","journal-title":"Genome Biol"},{"key":"2020050812275907800_ref40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12887-017-0976-8","article-title":"Preterm birth and the timing of puberty: a systematic review","volume":"18","author":"James","year":"2018","journal-title":"BMC Pediatr"},{"key":"2020050812275907800_ref41","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"2020050812275907800_ref42","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrg3230","article-title":"Functions of DNA methylation: islands, start sites, gene bodies and beyond","volume":"13","author":"Jones","year":"2012","journal-title":"Nat Rev Genet"},{"key":"2020050812275907800_ref43","doi-asserted-by":"crossref","first-page":"4953","DOI":"10.1210\/jc.2009-1789","article-title":"Early age at menarche associated with cardiovascular disease and mortality","volume":"94","author":"Lakshman","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2020050812275907800_ref44","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13059-015-0600-x","article-title":"A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies","volume":"16","author":"Lehne","year":"2015","journal-title":"Genome Biol"},{"key":"2020050812275907800_ref45","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.tig.2015.03.002","article-title":"The alternative role of DNA methylation in splicing regulation","volume":"31","author":"Lev Maor","year":"2015","journal-title":"Trends Genet"},{"key":"2020050812275907800_ref46","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.diabet.2017.01.002","article-title":"Early age at menarche and gestational diabetes mellitus risk: results from the Healthy Baby Cohort study","volume":"43","author":"Li","year":"2017","journal-title":"Diabetes Metab"},{"key":"2020050812275907800_ref47","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.neuropharm.2012.08.006","article-title":"Effects of metabotropic glutamate receptor ligands on male sexual behavior in rats","volume":"66","author":"Li","year":"2013","journal-title":"Neuropharmacology"},{"key":"2020050812275907800_ref48","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/MOP.0000000000000386","article-title":"Control of the onset of puberty","volume":"28","author":"Livadas","year":"2016","journal-title":"Curr Opin Pediatr"},{"key":"2020050812275907800_ref49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000438840","article-title":"The emerging role of epigenetics in the regulation of female puberty","volume":"29","author":"Lomniczi","year":"2016","journal-title":"Endocr Dev"},{"key":"2020050812275907800_ref50","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1164\/rccm.201802-0274OC","article-title":"Association of height growth in puberty with lung function a longitudinal study","volume":"198","author":"Mahmoud","year":"2018","journal-title":"Am J Resp Crit Care"},{"key":"2020050812275907800_ref51","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1136\/adc.44.235.291","article-title":"Variations in pattern of pubertal changes in girls","volume":"44","author":"Marshall","year":"1969","journal-title":"Arch Dis Child"},{"key":"2020050812275907800_ref52","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1136\/adc.45.239.13","article-title":"Variations in the pattern of pubertal changes in boys","volume":"45","author":"Marshall","year":"1970","journal-title":"Arch Dis Child"},{"key":"2020050812275907800_ref53","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1111\/j.1365-2605.2012.01286.x","article-title":"Age at puberty and risk of testicular cancer: a meta-analysis","volume":"35","author":"Maule","year":"2012","journal-title":"Int J Androl"},{"key":"2020050812275907800_ref54","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.dr.2011.11.001","article-title":"Detrimental psychological outcomes associated with pubertal timing in adolescent boys","volume":"32","author":"Mendle","year":"2012","journal-title":"Dev Rev"},{"key":"2020050812275907800_ref55","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.dr.2006.11.001","article-title":"Detrimental psychological outcomes associated with early pubertal timing in adolescent girls","volume":"27","author":"Mendle","year":"2007","journal-title":"Dev Rev"},{"key":"2020050812275907800_ref56","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller","year":"1988","journal-title":"Nucleic Acids Res"},{"key":"2020050812275907800_ref57","doi-asserted-by":"crossref","first-page":"F1736","DOI":"10.1152\/ajprenal.00221.2007","article-title":"Vesico-ureteric reflux and urinary tract development in the Pax2 1Neu+\/\u2212 mouse","volume":"293","author":"Murawski","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"key":"2020050812275907800_ref58","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/mrd.1080250305","article-title":"Male accessory sex glands produce heparin-binding proteins that bind to cauda epididymal spermatozoa and are testosterone dependent","volume":"25","author":"Nass","year":"1990","journal-title":"Mol Reprod Dev"},{"key":"2020050812275907800_ref59","doi-asserted-by":"crossref","first-page":"8263","DOI":"10.1038\/ncomms9263","article-title":"The fatty acid elongase Bond is essential for Drosophila sex pheromone synthesis and male fertility","volume":"6","author":"Ng","year":"2015","journal-title":"Nat Commun"},{"key":"2020050812275907800_ref60","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4161\/trns.19816","article-title":"A conserved role for intragenic DNA methylation in alternative pre-mRNA splicing","volume":"3","author":"Oberdoerffer","year":"2012","journal-title":"Transcription"},{"key":"2020050812275907800_ref61","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nrendo.2013.233","article-title":"Puberty in 2013: unravelling the mystery of puberty","volume":"10","author":"Ojeda","year":"2014","journal-title":"Nat Rev Endocrinol"},{"key":"2020050812275907800_ref62","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1210\/jc.2011-3445","article-title":"Timing of voice breaking in males associated with growth and weight gain across the life course","volume":"97","author":"Ong","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020050812275907800_ref63","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13545","article-title":"Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche","volume":"514","author":"Perry","year":"2014","journal-title":"Nature"},{"key":"2020050812275907800_ref64","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nrendo.2015.167","article-title":"Molecular insights into the aetiology of female reproductive ageing","volume":"11","author":"Perry","year":"2015","journal-title":"Nat Rev Endocrinol"},{"key":"2020050812275907800_ref65","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF01537962","article-title":"A self-report measure of pubertal status: reliability, validity, and initial norms","volume":"17","author":"Petersen","year":"1988","journal-title":"J Youth Adolesc"},{"key":"2020050812275907800_ref66","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.comppsych.2017.06.010","article-title":"Transdiagnostic psychiatric disorder risk associated with early age of menarche: a latent modeling approach","volume":"79","author":"Platt","year":"2017","journal-title":"Compr Psychiatry"},{"key":"2020050812275907800_ref67","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1016\/j.jchromb.2011.04.007","article-title":"D-Asp: a new player in reproductive endocrinology of the amphibian Rana esculenta","volume":"879","author":"Raucci","year":"2011","journal-title":"J Chromatogr B, Analyt Technol Biomed Life Sci"},{"key":"2020050812275907800_ref68","doi-asserted-by":"crossref","first-page":"e41361","DOI":"10.1371\/journal.pone.0041361","article-title":"Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility","volume":"7","author":"Reinius","year":"2012","journal-title":"PLoS One"},{"key":"2020050812275907800_ref69","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1210\/jc.2004-1991","article-title":"Early menarche and the development of cardiovascular disease risk factors in adolescent girls: the Fels Longitudinal Study","volume":"90","author":"Remsberg","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020050812275907800_ref70","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13072-017-0168-7","article-title":"Treatment with a DNA methyltransferase inhibitor feminizes zebrafish and induces long-term expression changes in the gonads","volume":"10","author":"Ribas","year":"2017","journal-title":"Epigenetics Chromatin"},{"key":"2020050812275907800_ref71","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/1756-0500-5-210","article-title":"Quantitative cross-validation and content analysis of the 450k DNA methylation array from Illumina, Inc","volume":"5","author":"Roessler","year":"2012","journal-title":"BMC Res Notes"},{"key":"2020050812275907800_ref72","doi-asserted-by":"crossref","first-page":"e1003572","DOI":"10.1371\/journal.pgen.1003572","article-title":"A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue","volume":"9","author":"Ronn","year":"2013","journal-title":"PLoS Genet"},{"key":"2020050812275907800_ref73","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.jhep.2014.11.041","article-title":"Age at menarche and non-alcoholic fatty liver disease","volume":"62","author":"Ryu","year":"2015","journal-title":"J Hepatol"},{"key":"2020050812275907800_ref74","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1093\/oxfordjournals.jbchem.a021655","article-title":"Structural and functional characterization of the human brain D-aspartate oxidase","volume":"121","author":"Setoyama","year":"1997","journal-title":"J Biochem"},{"key":"2020050812275907800_ref75","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/bjc.2011.550","article-title":"Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research","volume":"106","author":"Shenker","year":"2012","journal-title":"Br J Cancer"},{"key":"2020050812275907800_ref76","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1111\/j.1530-0277.2011.01525.x","article-title":"Hypothalamic actions and interactions of alcohol and IGF-1 on the expression of glial receptor protein tyrosine phosphatase-beta during female pubertal development","volume":"35","author":"Srivastava","year":"2011","journal-title":"Alcohol Clin Exp Res"},{"key":"2020050812275907800_ref77","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13148-018-0491-2","article-title":"Global DNA methylation changes spanning puberty are near predicted estrogen-responsive genes and enriched for genes involved in endocrine and immune processes","volume":"10","author":"Thompson","year":"2018","journal-title":"Clin Epigenetics"},{"key":"2020050812275907800_ref78","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/ajcn\/64.1.18","article-title":"Rapid maturation in adolescence results in greater obesity in adulthood: the Amsterdam Growth and Health Study","volume":"64","author":"van Lenthe","year":"1996","journal-title":"Am J Clin Nutr"},{"key":"2020050812275907800_ref79","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1164\/rccm.200405-674OC","article-title":"Epidemiological Study on the G, Environment of A. Asthma severity is associated with body mass index and early menarche in women","volume":"171","author":"Varraso","year":"2005","journal-title":"Am J Resp Crit Care"},{"key":"2020050812275907800_ref80","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000438957","article-title":"Normal variation in pubertal timing: genetic determinants in relation to growth and adiposity","volume":"29","author":"Willemsen","year":"2016","journal-title":"Endocr Dev"},{"key":"2020050812275907800_ref81","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2174\/1389203711314010009","article-title":"Heparin and heparin binding proteins: potential relevance to reproductive physiology","volume":"14","author":"Yadav","year":"2013","journal-title":"Curr Protein Pept Sci"},{"key":"2020050812275907800_ref82","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.ijcard.2016.10.115","article-title":"Age at menarche and risk of major cardiovascular diseases: evidence of birth cohort effects from a prospective study of 300,000 Chinese women","volume":"227","author":"Yang","year":"2017","journal-title":"Int J Cardiol"},{"key":"2020050812275907800_ref83","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1186\/s12864-015-1572-7","article-title":"Quantitative and multiplexed DNA methylation analysis using long-read single-molecule real-time bisulfite sequencing (SMRT-BS)","volume":"16","author":"Yang","year":"2015","journal-title":"BMC Genomics"},{"key":"2020050812275907800_ref84","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3345\/kjp.2016.59.9.355","article-title":"Effects of early menarche on physical and psychosocial health problems in adolescent girls and adult women","volume":"59","author":"Yoo","year":"2016","journal-title":"Korean J Pediatr"},{"key":"2020050812275907800_ref85","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1093\/humrep\/des022","article-title":"SEMA3A deletion in a family with Kallmann syndrome validates the role of semaphorin 3A in human puberty and olfactory system development","volume":"27","author":"Young","year":"2012","journal-title":"Hum Reprod"},{"key":"2020050812275907800_ref86","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s12519-013-0399-z","article-title":"Relationships between age of puberty onset and height at age 18 years in girls and boys","volume":"9","author":"Yousefi","year":"2013","journal-title":"World J Pediatr"}],"container-title":["Human Reproduction Open"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hropen\/article-pdf\/2020\/2\/hoaa006\/33193168\/hoaa006.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hropen\/article-pdf\/2020\/2\/hoaa006\/33193168\/hoaa006.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T19:01:02Z","timestamp":1722366062000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hropen\/article\/doi\/10.1093\/hropen\/hoaa006\/5802390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":88,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/hropen\/hoaa006","relation":{},"ISSN":["2399-3529"],"issn-type":[{"value":"2399-3529","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020]]},"published":{"date-parts":[[2020]]},"article-number":"hoaa006"}}