ArticleNature genetics2024
Understanding the genetic complexity of puberty timing across the allele frequency spectrum.
Erratum issuedAbstract read
In one paragraph
Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Lifecourse genome-wide association study meta-analysis refines the critical life stages for adiposity's influence on breast cancer risk.Science advances · 2026Pooled it
- A single-nuclei multiomics resource across four brain regions prioritises human neural cell types influencing brain-related traits.bioRxiv : the preprint server for biology · 2026Article
- Genome-wide mapping of common and rare variant effects on adiposity across childhood.Nature genetics · 2026Article
- Distinct body mass index trajectories throughout childhood in girls with early puberty.Pediatric research · 2026Article
- Obesity, Oxidative Stress, and Inflammation in Precocious Puberty: Do All Roads Lead to the Hypothalamus?International journal of molecular sciences · 2026Review
- CYP19A1 variation in healthy children: associations with breast development and pubertal gynecomastia.Endocrine connections · 2026Article
- Goodbye, idiopathic short stature: why "healthy short stature" is a necessary advancement.Archives of endocrinology and metabolism · 2026Article
- Mendelian randomization of risk factors for premenstrual disorders.Npj mental health research · 2026Article
- geneXplore: An Interactive Browser for X Chromosome-Wide Association Study Results.medRxiv : the preprint server for health sciences · 2026Article
- Age at menarche and adverse pregnancy and perinatal outcomes: triangulating evidence from multivariable and Mendelian randomization analyses.International journal of epidemiology · 2026Article
- Large-scale analysis of FMR1 CGG repeat length and risk of premature ovarian insufficiency in over 92 000 women.Human reproduction (Oxford, England) · 2026Article
- Natural menopause, menarche and breast cancer risk in BRCA1 and BRCA2 pathogenic variant carriers: a Mendelian randomization analysis.British journal of cancer · 2026Article
- Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.Nature genetics · 2026Article
- Shared Risk Genes and Casual Relationships across Sex Hormone Related Traits and Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2026Article
- <italic>MKRN3</italic> Variants in Central Precocious Puberty as an Example of the Complexity to Classify Missense Variants in Imprinted Genes as Pathogenic.Hormone research in paediatrics · 2026Article
- Free testosterone and IGF-I mediate sex-specific linear growth during minipuberty.Endocrine connections · 2026Article
- Article
- Nanoplastics Impair GnRH Neuron Migration and Neuroendocrine Function: Emerging Players in the Pathogenesis of Reproductive Disorders.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Leveraging protein language models to identify complex trait associations with previously inaccessible classes of functional rare variants.Cell genomics · 2026Article
- Clinical and genetic evidence from East Asian cohorts linking family history burden and menarche timing to curve severity in adolescent idiopathic scoliosis.Frontiers in endocrinology · 2026Article
Corrections and comments
- Erratum issued
- Update of
Authors and funding
227 authors.
Katherine A Kentistou *MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-5816-664X
Lena R Kaisinger *MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-0849-3191
Stasa StankovicMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-6602-1379
Marc VaudelMohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway.ORCID http://orcid.org/0000-0003-1179-9578
Edson Mendes de OliveiraUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Andrea MessinaDivision of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-2393-1874
Robin G WaltersNuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9179-0321
Xiaoxi LiuLaboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Alexander S BuschDepartment of General Pediatrics, University of Münster, Münster, Germany.
Hannes HelgasondeCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Deborah J ThompsonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Federico SantoniDivision of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-3258-4747
Konstantin M PetricekCharité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, Germany.ORCID http://orcid.org/0000-0002-3352-093X
Yassine ZouaghiDivision of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Isabel Huang-DoranUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Daniel F GudbjartssondeCODE Genetics/Amgen, Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-5222-9857
Eirik BratlandMohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway.
Kuang LinNuffield Department of Population Health, University of Oxford, Oxford, UK.
Eugene J GardnerMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0001-9671-1533
Yajie ZhaoMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-2747-0219
Raina Y JiaMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Chikashi TeraoLaboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.ORCID http://orcid.org/0000-0002-6452-4095
Marjorie J RigganDepartment of Gynecology, Duke University Medical Center, Durham, NC, USA.
Manjeet K BollaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Mojgan YazdanpanahResearch Center of the Sainte-Justine University Hospital, University of Montreal, Montreal, Quebec, Canada.
Nahid YazdanpanahResearch Center of the Sainte-Justine University Hospital, University of Montreal, Montreal, Quebec, Canada.
Jonathan P BradfieldQuantinuum Research, Wayne, PA, USA.
Linda BroerDepartment of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-0011-123X
Archie CampbellCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-0198-5078
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3357-0862
Diana L CousminerDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Nora FranceschiniDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0009-0001-8346-3662
Lude H FrankeDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-5159-8802
Giorgia GirottoInstitute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy.ORCID http://orcid.org/0000-0003-4507-6589
Chunyan HeDepartment of Internal Medicine, Division of Medical Oncology, University of Kentucky College of Medicine, Lexington, KY, USA.
Marjo-Riitta JärvelinDepartment of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-2149-0630
Peter K JoshiCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, Scotland.
Yoichiro KamataniLaboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-8748-5597
Robert KarlssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-8949-2587
Jian'an LuanMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0003-3137-6337
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9268-810X
Reedik MägiInstitute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0002-2964-6011
Massimo ManginoDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-2167-7470
Sarah E MedlandQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0003-1382-380X
Christa MeisingerEpidemiology, Medical Faculty, University of Augsburg, University Hospital of Augsburg, Augsburg, Germany.
Raymond NoordamDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-7801-809X
Teresa NutileInstitute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples, Italy.
Maria Pina ConcasInstitute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy.ORCID http://orcid.org/0000-0003-3598-2537
Ozren PolašekUniversity of Split School of Medicine, Split, Croatia.
Eleonora PorcuInstitute of Genetics and Biomedical Research, National Research Council, Sardinia, Italy.
Susan M RingMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0003-3103-9330
Cinzia SalaDivision of Genetics and Cell Biology, San Raffele Hospital, Milano, Italy.ORCID http://orcid.org/0000-0003-2514-2075
Albert V SmithIcelandic Heart Association, Kopavogur, Iceland.ORCID http://orcid.org/0000-0003-1942-5845
Toshiko TanakaNational Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Peter J van der MostDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0001-8450-3518
Veronique VitartMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Carol A WangSchool of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.ORCID http://orcid.org/0000-0002-4301-3974
Gonneke WillemsenDepartment of Biological Psychology, Vrije Universiteit Amsterdam; Amsterdam Public Health (APH) Research Institute, Amsterdam, The Netherlands.
Marek ZygmuntClinic of Gynaecology and Obstetrics, University Medicine Greifswald, Greifswald, Germany.
Thomas U AhearnDivision of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health, Department of Health and Human Services Bethesda, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0771-7752
Irene L AndrulisFred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-4226-6435
Hoda Anton-CulverDepartment of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA.
Antonis C AntoniouCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Paul L AuerDivision of Biostatistics, Institute for Health and Equity and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.ORCID http://orcid.org/0000-0003-1735-8044
Catriona L K BarnesCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, Scotland.
Matthias W BeckmannDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
Amy Berrington de GonzalezDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Natalia V BogdanovaDepartment of Radiation Oncology, Hannover Medical School, Hannover, Germany.
Stig E BojesenCopenhagen General Population Study, Herlev and Gentofte Hospital Copenhagen University Hospital, Herlev, Denmark.ORCID http://orcid.org/0000-0002-4061-4133
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-6129-1572
Julie E BuringDivision of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8919-1971
Fergus J CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Rochester, MN, USA.
Angela CoxSheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
Laura CrisponiInstitute of Genetics and Biomedical Research, National Research Council, Sardinia, Italy.ORCID http://orcid.org/0000-0001-9128-8537
Kamila CzeneDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mary B DalyDepartment of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
Ellen W DemerathDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Joe DennisCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-4591-1214
Peter DevileeDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-8023-2009
Immaculata De VivoDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Thilo DörkGynaecology Research Unit, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0002-9458-0282
Alison M DunningCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-6651-7166
Miriam DwekSchool of Life Sciences, University of Westminster, London, UK.ORCID http://orcid.org/0000-0001-7184-2932
Johan G ErikssonDepartment of General Practice and Primary Healthcare, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Peter A FaschingDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.ORCID http://orcid.org/0000-0003-4885-8471
Lindsay Fernandez-RhodesDepartment of Biobehavioral Health, Pennsylvania State University, University Park, PA, USA.ORCID http://orcid.org/0000-0001-6985-423X
Liana FerreliInstitute of Genetics and Biomedical Research, National Research Council, Sardinia, Italy.
Olivia FletcherThe Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0001-9387-7116
Manuela Gago-DominguezGenomic Medicine Group, International Cancer Genetics and Epidemiology Group Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS Santiago de Compostela, Coruña, Spain.
Montserrat García-ClosasDivision of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health, Department of Health and Human Services Bethesda, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1033-2650
José A García-SáenzMedical Oncology Department, Hospital Clínico San Carlos Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.ORCID http://orcid.org/0000-0001-6880-0301
Anna González-NeiraHuman Genotyping Unit-CeGen, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Harald GrallertResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Pascal GuénelTeam 'Exposome and Heredity', CESP, Gustave Roussy INSERM, University Paris-Saclay, UVSQ, Orsay, France.ORCID http://orcid.org/0000-0002-8359-518X
Christopher A HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Per HallDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ute HamannMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Hakon HakonarsonCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2814-7461
Roger J HartDivision of Obstetrics and Gynaecology, University of Western Australia, Crawley, Western Australia, Australia.
Martha HickeyDepartment of Obstetrics and Gynaecology, University of Melbourne and The Royal Women's Hospital, Parkville, Victoria, Australia.
Maartje J HooningDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Reiner HoppeDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
John L HopperCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
Jouke-Jan HottengaDepartment of Biological Psychology, Vrije Universiteit Amsterdam; Amsterdam Public Health (APH) Research Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-5668-2368
Frank B HuChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Hanna HuebnerDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.ORCID http://orcid.org/0000-0001-6889-1493
David J HunterNuffield Department of Population Health, University of Oxford, Oxford, UK.
ABCTB Investigators
Helena JernströmOncology, Department of Clinical Sciences in Lund, Lund University, Lund, Sweden.
Esther M JohnDepartment of Epidemiology and Population Health, Stanford University School of Medicine Stanford, Stanford, CA, USA.
David KarasikHebrew SeniorLife Institute for Aging Research, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8826-0530
Elza K KhusnutdinovaInstitute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
Vessela N KristensenDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.ORCID http://orcid.org/0000-0001-5012-7438
James V LaceyDepartment of Computational and Quantitative Medicine, City of Hope, Duarte, CA, USA.
Diether LambrechtsLaboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
Lenore J LaunerLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3238-7612
Penelope A LindQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-3887-2598
Annika LindblomDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Patrik K E MagnussonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-7315-7899
Arto MannermaaTranslational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
Mark I McCarthyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-4393-0510
Thomas MeitingerInstitute of Human Genetics, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany.ORCID http://orcid.org/0000-0002-8838-8403
Cristina MenniDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID http://orcid.org/0000-0001-9790-0571
Kyriaki MichailidouCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-7065-1237
Iona Y MillwoodNuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-0807-0682
Roger L MilneCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0001-5764-7268
Grant W MontgomeryInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-4140-8139
Heli NevanlinnaDepartment of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-0916-2976
Ilja M NolteDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0001-5047-4077
Dale R NyholtSchool of Biomedical Sciences, Faculty of Health, Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0001-7159-3040
Nadia ObiInstitute for Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Katie M O'BrienEpidemiology Branch, National Institute of Environmental Health Sciences, NIH Research Triangle Park, Durham, NC, USA.
Kenneth OffitClinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
Albertine J OldehinkelInterdisciplinary Center Psychopathology and Emotion Regulation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0003-3925-3913
Sisse R OstrowskiDepartment of Clinical Immunology, Rigshospitalet-University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-5288-3851
Aarno PalotiePsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2527-5874
Ole B PedersenDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-2312-5976
Annette PetersInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Giulia PianigianiInstitute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy.
Dijana Plaseska-KaranfilskaResearch Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', MASA, Skopje, Republic of North Macedonia.ORCID http://orcid.org/0000-0001-8877-2416
Anneli PoutaNational Institute for Health and Welfare, Helsinki, Finland.
Alfred PozarickijNuffield Department of Population Health, University of Oxford, Oxford, UK.
Paolo RadiceUnit of Preventive Medicine: Molecular Bases of Genetic Risk, Department of Experimental Oncology, Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, Italy.ORCID http://orcid.org/0000-0001-6298-4111
Gad RennertFaculty of Medicine, Clalit National Cancer Control Center, Carmel Medical Center and Technion, Haifa, Israel.ORCID http://orcid.org/0000-0002-8512-068X
Frits R RosendaalDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0003-2558-7496
Daniela RuggieroInstitute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples, Italy.
Emmanouil SaloustrosDivision of Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.ORCID http://orcid.org/0000-0002-0485-0120
Dale P SandlerEpidemiology Branch, National Institute of Environmental Health Sciences, NIH Research Triangle Park, Durham, NC, USA.ORCID http://orcid.org/0000-0002-6776-0018
Sabine SchipfInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Carsten O SchmidtInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0001-5266-9396
Marjanka K SchmidtDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-2228-429X
Kerrin SmallDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID http://orcid.org/0000-0003-4566-0005
Beatrice SpedicatiDepartment of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.ORCID http://orcid.org/0000-0002-7432-4708
Meir StampferDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jennifer StoneCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0001-5077-0124
Rulla M TamimiDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Lauren R TerasDepartment of Population Science, American Cancer Society, Atlanta, GA, USA.ORCID http://orcid.org/0000-0003-2419-8536
Emmi TikkanenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Constance TurmanDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Celine M VachonDepartment of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic Rochester, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-1962-9322
Qin WangCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Robert WinqvistLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland.ORCID http://orcid.org/0000-0003-0932-9104
Alicja WolkInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-7387-6845
Babette S ZemelDepartment of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Ko W van DijkDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-2172-7394
Behrooz Z AlizadehDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Stefania BandinelliGeriatric Unit, Local Health Toscana Centro, Florence, Italy.
Eric BoerwinkleHuman Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
Dorret I BoomsmaDepartment of Biological Psychology, Vrije Universiteit Amsterdam; Amsterdam Public Health (APH) Research Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-7099-7972
Marina CiulloInstitute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples, Italy.
Georgia Chenevix-TrenchQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Francesco CuccaInstitute of Genetics and Biomedical Research, National Research Council, Sardinia, Italy.
Tõnu EskoInstitute of Genomics, University of Tartu, Tartu, Estonia.
Christian GiegerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-6986-9554
Struan F A GrantDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2025-5302
Vilmundur GudnasonIcelandic Heart Association, Kopavogur, Iceland.ORCID http://orcid.org/0000-0001-5696-0084
Caroline HaywardMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-9405-9550
Ivana KolčićUniversity of Split School of Medicine, Split, Croatia.
Peter KraftDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Deborah A LawlorMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-6793-2262
Nicholas G MartinQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0003-4069-8020
Ellen A NøhrInstitute of Clinical Research, University of Southern Denmark, Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark.
Nancy L PedersenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Craig E PennellSchool of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.ORCID http://orcid.org/0000-0002-0937-6165
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Antonietta RobinoInstitute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0003-1949-2298
Ulla SovioDepartment of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-0799-1105
Tim D SpectorDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-9795-0365
Doris StöcklInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Cathie SudlowCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Nic J TimpsonMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-7141-9189
Daniela TonioloDivision of Genetics and Cell Biology, San Raffele Hospital, Milano, Italy.
André UitterlindenDepartment of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-7276-3387
Sheila UliviInstitute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy.
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0003-1422-2993
Elisabeth WidenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
James F WilsonCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, Scotland.ORCID http://orcid.org/0000-0001-5751-9178
Lifelines Cohort Study
Danish Blood Donor Study
Ovarian Cancer Association Consortium
Breast Cancer Association Consortium
Biobank Japan Project
China Kadoorie Biobank Collaborative Group
Paul D P PharoahCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-8494-732X
Liming LiDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.ORCID http://orcid.org/0000-0001-5873-7089
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-2444-3247
Pål R NjølstadMohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway.ORCID http://orcid.org/0000-0003-0304-6728
Patrick SulemdeCODE Genetics/Amgen, Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0001-7123-6123
Joanne M MurabitoNHLBI's and Boston University's Framingham Heart Study, Framingham, MA, USA.
Anna MurrayGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, RILD Level 3, Royal Devon and Exeter Hospital, Exeter, UK.ORCID http://orcid.org/0000-0002-2351-2522
Despoina ManousakiCentre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, University of Montreal, Montreal, Quebec, Canada.
Anders JuulDepartment of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-0534-4350
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-6551-6647
Kari StefanssondeCODE Genetics/Amgen, Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-1676-864X
Momoko HorikoshiLaboratory for Genomics of Diabetes and Metabolism, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.ORCID http://orcid.org/0000-0002-7103-2267
Zhengming ChenNuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-6423-105X
I Sadaf FarooqiUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Nelly PitteloudDivision of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Stefan JohanssonMohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway.ORCID http://orcid.org/0000-0002-2298-7008
Felix R Day *MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0003-3789-7651
John R B Perry *MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK. john.perry@mrc-epid.cam.ac.uk.ORCID http://orcid.org/0000-0001-6483-3771
Ken K Ong *MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0003-4689-7530
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MUNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A. Troester · 2001 to 2026
$36.3MEnvironmental and Genetic Risk Factors For Breast Cancer: The Sister StudyZIAES044005 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI SANDLER, DALE P · 2009 to 2025
$22.7MCLINICAL PROJECT: Age, Gene/Environment Susceptibility Study on the Multi-omics of Aging: A clinical epidemiologic prospective studyZIAAG007380 · NIA · NATIONAL INSTITUTE ON AGING · PI LAUNER, LENORE J · 2009 to 2025
$6.1MGenomics of bone and body composition traits in childrenR01HD100406 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI GRANT, STRUAN F A, ZEMEL, BABETTE S · 2020 to 2024
$3.4MMedical Research Council MC_UU_00006/2NCI NIH HHS P30 CA008748NICHD NIH HHS R01 HD100406NIEHS NIH HHS P30 ES010126RCUK | MRC | Medical Research Foundation MC_UU_00006/2
Abstract
Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.
Indexed as
Gene FrequencyMenarchePubertyAdolescentAnimalsChildFemaleGenome-Wide Association StudyHumansMiceMultifactorial InheritancePolymorphism, Single NucleotidePuberty, DelayedPuberty, PrecociousReceptors, G-Protein-CoupledReceptors, G-Protein-Coupled
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.