{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Day FR"],"funding":["Intramural NIH HHS","Cancer Research UK","British Heart Foundation","NICHD NIH HHS","NIA NIH HHS","Medical Research Council","NHLBI NIH HHS","The Francis Crick Institute","National Institute for Health Research (NIHR)","NCI NIH HHS","Cancer Foundation Finland sr","Wellcome Trust"],"pagination":["834-841"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5841952"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["49(6)"],"pubmed_abstract":["The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10<sup>-8</sup>) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, indepe"],"journal":["Nature genetics"],"pubmed_title":["Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk."],"pmcid":["PMC5841952"],"funding_grant_id":["UM1 CA182913","MC_UU_12013/3","MC_UU_12015/1","MC_UU_12013/1","MC_EX_MR/L100002/1","202802/Z/16/Z","NF-SI-0611-10099","MR/J012165/1","Z01 AG006000","14136","T32 HL007055","MC_PC_13046","16561","G1000143","MC_PC_13048","16565","110135","SP/07/008/24066","G1001357","130168","NF-SI-0512-10114","MR/N003284/1","MC_UU_12013/5","R01 CA192393","MC_UU_12015/2","P2C HD050924","150147","NF-SI-0512-10135","G0401527","R56 AG029451","MC_PC_U127561128","10124"],"pubmed_authors":["Flesch-Janys D","Southey MC","Martin NG","Uitterlinden AG","Lunetta KL","Luan J","Menni C","van Dijk KW","Zhao JH","Sorice R","kConFab/AOCS Investigators","Easton DF","LifeLines Cohort Study","Stolk L","Thompson DJ","He C","Nolte IM","Esko T","Ciullo M","Buring JE","Milani L","Gandin I","Corre T","Robino A","Mbarek H","Hall P","Hooning MJ","Hu F","Strauch K","Amini M","Broer L","Scott RA","Murabito JM","Karasik D","Thorsteindottir U","Tyrer JP","Pollard KS","Cousminer DL","Bojesen SE","Timpson NJ","Nyholt DR","McMahon G","Smith AV","Widen E","Ridker PM","Heiss G","Fernandez-Rhodes L","Day FR","Spurdle AB","Kellis M","Volker U","Sulem P","Lambrechts D","PRACTICAL consortium","Tikkanen E","Vollenweider P","Alizadeh BZ","Rose LM","Tung JY","Grallert H","Peters A","Pouta A","de Geus EJCN","Guenel P","Pharoah PDP","Wilson JF","Murray A","Medland SE","Zoledziewska M","Sarkar AK","Chenevix-Trench G","Gieger C","Li J","Milne RL","Magi R","Willemsen G","Franceschini N","Meisinger C","Fasching PA","Eriksson JG","Jarvelin MR","Schmidt MK","de Mutsert R","Nevanlinna H","Lawlor DA","Davey Smith G","Michailidou K","Hallberg E","Lenarduzzi S","Schraut KE","Padmanabhan S","Hunter DJ","Liu Y","Radice P","Mangino M","Lind PA","Perry JRB","Hottenga JJ","Montgomery GW","Pedersen N","Metspalu A","Sovio U","Snieder H","Dennis J","Navarro P","Brand JS","Steri M","Marco B","Launer LJ","Gudbjartsson DF","Mannermaa A","Bruning T","McCarthy MI","Shah M","Ring SM","Ulivi S","Volzke H","Hartman CA","Rosendaal FR","Sala CF","Gudnason V","Palotie A","Chasman DI","Ikram MA","Mook-Kanamori DO","Porcu E","Oldehinkel AJ","Barbieri CM","Cucca F","Hayward C","Loh PR","Segre AV","Porteous D","Stampfer M","Magnusson PKE","Traglia M","Price AL","Visser JA","Peto J","Ong KK","Crisponi L","Harris TB","Brenner H","Noordam R","Truong T","Winqvist R","Perjakova N","Bergmann S","Nalls MA","Franke L","Brauch H","Rueedi R","Nohr EA","Bochud M","Albrecht E","Paternoster L","Benitez J","Tanaka T","Wareham NJ","InterAct Consortium","Boomsma DI","Cox A","Im HK","Teumer A","Ruggiero D","Dunning AM","Finucane H","Karlsson R","Toniolo D","Endometrial Cancer Association Consortium","Kolcic I","Andrulis IL","Edwards DRV","Stefansson K","Helgason H","Boerwinkle E","Wang Q","Catamo E","Ferrucci L","Spector TD","Couch FJ","Meitinger T","Joshi PK","Bolla MK","Chang-Claude J","Rahman I","Ovarian Cancer Association Consortium","Mulligan AM","Altmaier E","Gabrielson M","O'Mara TA","Stockl D","Kraft P","Giri A","Zygmunt M","Kutalik Z","Polasek O","Chanock S","Nutile T","Hinds D","Whalen S","Demerath E","Wolffenbuttel BHR","Bandinelli S","Beckmann MW","Devilee P","Giles GG","De Vivo I","Laven JSE","Czene K","Rudan I","LaChance G","Ruth KS","Vitart V","Langenberg C","Campbell H","Dos-Santos-Silva I","Hopper JL","Lindstrom S","Campbell A","Boutin T","Hamann U"],"additional_accession":[]},"is_claimable":false,"name":"Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.","description":"The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10<sup>-8</sup>) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, indepe","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Jun","modification":"2026-05-04T17:45:27.709Z","creation":"2019-03-26T23:39:02Z"},"accession":"S-EPMC5841952","cross_references":{"pubmed":["28436984"],"doi":["10.1038/ng.3841"]}}