{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Day FR"],"funding":["Cancer Research UK","NCATS NIH HHS","NIA NIH HHS","NCRR NIH HHS","NIDA NIH HHS","NHLBI NIH HHS","Cancer Foundation Finland sr","NIDDK NIH HHS","Medical Research Council","The Francis Crick Institute","NHGRI NIH HHS","Chief Scientist Office","National Institute for Health Research (NIHR)","NCI NIH HHS","Wellcome Trust","WHI NIH HHS"],"pagination":["1294-1303"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4661791"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["47(11)"],"pubmed_abstract":["Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization "],"journal":["Nature genetics"],"pubmed_title":["Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair."],"pmcid":["PMC4661791"],"funding_grant_id":["N.1-AG-1-2111","C12292/A11174","C1287/A10118","C1281/A12014","N.1-AG-1-1","HL087652","HL080467","P30 DK072488","CA164920","HHSN268201100009C","1233641","HHSN271201100005C","HHSN268201100001C","HL087660","UL1 TR000124","130168","HG005552","HHSN268200800007C","HL054457","HG006513","RC4 AG039029","1U19 CA148112","P30 DK063491","MC_PC_U127561128","HHSN268201100002C","HL043851","UM1 CA182910","CZB/4/710","UM1 CA182913","N01-HC-95161","HG007022","N01-HC-95160","N01-HC-95159","HHSN268201100003C","10119","HHSN268200782096C","R21AG032598","N02-HL-6-4278","03/DHCS/03/G121/51","16459","15007","CZD/16/6/4","N01AG62106","AG023629","HL054464","N01AG62101","N01AG62103","1U19 CA148537","U01-HL84756","UL1TR000124","MC_PC_13048","11174","HL080295","MC_U106179472","AG009740","MC_U106179471","HL105756","HHSN268201100004C","C5047/A8384","NF-SI-0514-10027","10124","R01AG29451","C5047/A15007","C5047/A10692","K01-HL116770","N01-HC-25195","HG007089","HG005581","090532","HHSN268201100005C","N01-AG-5-0002","HL054481","17528","P30-DK072488","R01HL087641","16561","U01 AG009740","16565","16563","R01DK075787","U01AG009740","1R01AG032098-01A1","HHSN268201100006C","R01HL59367","R01 HL087660","N01HC85079","DK063491","HHSN268201100010C","HHSN268201100046C","N01-AG-1-2109","C8197/A16565","UL1 TR001108","N01HC85081","MC_UU_12015/1","N01HC85082","U01-HL72515","N01HC85080","HHSN268201200036C","N01HC85086","HHSN268201100007C","N01HC85083","R01 HL119443","1U19 CA148065","HHSN268201100011C","RC2 AG036495","P30 CA015704","C1287/A 10710","UL1RR025005","N01HC55222","MC_UU_12015/2","HHSN268201100008C","U01HG004402","NF-SI-0512-10135","HHSN271201100004C","CA128978","R21 AG032598","5RC2HL102419","HHSN268201100012C"],"pubmed_authors":["Flesch-Janys D","Psaty BM","Southey MC","Kardia SLR","Martin NG","Uitterlinden AG","Generation Scotland","Lunetta KL","Luan J","Sorice R","Burwinkel B","Easton DF","Kabisch M","LifeLines Cohort Study","Stolk L","Thompson DJ","He C","Zemunik T","Esko T","Weir DR","Ciullo M","Milani L","Buring JE","Gandin I","Corre T","Robino A","Hall P","Hooning MJ","Strauch K","Schmutzler RK","Figueroa J","McKnight B","Scott RA","Thorsteinsdottir U","Neale BM","Murabito JM","Rudolph A","Karasik D","Huffman JE","Manz J","Zhao W","Bojesen SE","Bogdanova NV","Smith AV","Raffel LJ","Boutin TS","Taylor KD","Ridker PM","Peterlongo P","Vozzi D","Day FR","Pirastu NN","Turner ST","Rivadeneira F","Sulem P","Lambrechts D","Wolffenbuttel BBHR","PRACTICAL consortium","Faul JD","Bielinski SJ","Henderson BE","Beeghly-Fadiel A","Alizadeh BZ","Rose LM","Grove ML","Garcia-Closas M","Rotter JI","Toland AE","Antoniou AC","Sanna S","Seynaeve CM","Guenel P","Pharoah PDP","Wilson JF","Murray A","Nordestgaard BG","Peters U","Jones SE","Simard J","Chenevix-Trench G","Keller MF","Abecasis G","Chanock SJ","Pirie A","Schoemaker MJ","Gieger C","Hu FB","Li J","Milne RL","Magi R","Willemsen G","Franceschini N","Fasching PA","van Duijn CM","Li X","Schmidt MK","Nevanlinna H","Goodarzi MO","Michailidou K","Muller-Nurasyid M","Tryggvadottir L","Swerdlow A","Pylkas K","Padmanabhan S","Hunter DJ","Liu Y","Radice P","Yannoukakos D","Mangino M","Haiman CA","Perry JRB","Hottenga JJ","Schick UM","Montgomery GW","Homuth G","Metspalu A","Dennis J","Pervjakova N","Sawyer EJ","Olson JE","Gudbjartsson DF","Jakubowska A","Mannermaa A","Bruning T","Dork T","Ulivi S","Volzke H","Guo X","Hocking LJ","Sala CF","Gudnason V","Lubinski J","Morrison AC","Chasman DI","Eicher JD","Blomqvist C","Newman AB","Gasparini PP","Porcu E","Hayward C","Girotto GG","Darabi H","Bulik-Sullivan B","Porteous D","Zheng W","Traglia M","Price AL","EPIC-InterAct Consortium","Visser JA","Humphreys K","Peto J","Ong KK","Vuckovic D","Crisponi L","Harris TB","Brenner H","Truong T","Winqvist R","Bergmann S","Bernstein L","Amin N","Brauch H","Albrecht E","Kristensen V","Benitez J","AOCS Investigators","Tanaka T","Hofman A","Wareham NJ","Smith JA","Arnold AM","Garcia ME","Reiner AP","Knight JA","McArdle PF","Boomsma DI","Cox A","Barbieri C","Kooperberg C","Teumer A","Ruggiero D","Dunning AM","Petersmann A","Finucane HK","Toniolo D","Kosma VM","Andrulis IL","Goldberg MS","Huang J","Kolcic I","Stefansson K","Johnson AD","Boerwinkle E","Schmidt F","Masciullo C","Franke LL","Wang Q","Pistis G","Ferrucci L","Spector TD","Marten J","Couch FJ","Bolla MK","Yao J","Chang-Claude J","Coviello AD","Demerath EW","Wellons M","Wright AF","Yerges-Armstrong LM","Altmaier E","Brody JA","Neven P","Arndt V","Stockl D","Kraft P","Nalls M","Zygmunt M","Elks CE","Polasek O","Anton-Culver H","Nutile T","Tomlinson I","Schlessinger D","Mihailov E","Beckmann MW","Chapman JR","Devilee P","Giles GG","Borresen-Dale AL","Kriebel J","De Vivo I","Gonzalez-Neira A","Czene K","Rudan I","Margolin S","Ruth KS","Langenberg C","Campbell H","Dos-Santos-Silva I","Hopper JL","Lindstrom S","Campbell A","Chen YI","Hamann U","kConFab Investigators","Meindl A"],"additional_accession":[]},"is_claimable":false,"name":"Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.","description":"Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization ","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Nov","modification":"2026-05-05T08:12:36.555Z","creation":"2019-03-27T02:02:51Z"},"accession":"S-EPMC4661791","cross_references":{"pubmed":["26414677"],"doi":["10.1038/ng.3412"]}}