Cited by 294Hypothalamic control of reproductive hormonesGenetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and Animals

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Meta-analysis of genome-wide association data identifies two loci influencing age at menarche

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Perry, John R B, Stolk, Lisette, Franceschini, Nora, Lunetta, Kathryn L, Zhai, Guangju, McArdle, Patrick F, Smith, Albert V, Aspelund, Thor, Bandinelli, Stefania, Boerwinkle, Eric, Cherkas, Lynn, Eiriksdottir, Gudny, Estrada, Karol, Ferrucci, Luigi, Folsom, Aaron R, Garcia, Melissa, Gudnason, Vilmundur, Hofman, Albert, Karasik, David, Kiel, Douglas P, Launer, Lenore J, van Meurs, Joyce, Nalls, Michael A, Rivadeneira, Fernando, Shuldiner, Alan R, Singleton, Andrew, Soranzo, Nicole, Tanaka, Toshiko, Visser, Jenny A, Weedon, Michael N, Wilson, Scott G, Zhuang, Vivian, Streeten, Elizabeth A, Harris, Tamara B, Murray, Anna, Spector, Tim D, Demerath, Ellen W, Uitterlinden, André G, Murabito, Joanne M·2009·Nature Genetics

DOI 10.1038/ng.386PMC PMC2942986

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Abstract

We conducted a meta-analysis of genome-wide association data to detect genes influencing age at menarche in 17,510 women. The strongest signal was at 9q31.2 (P = 1.7 × 10(-9)), where the nearest genes include TMEM38B, FKTN, FSD1L, TAL2 and ZNF462. The next best signal was near the LIN28B gene (rs7759938; P = 7.0 × 10(-9)), which also influences adult height. We provide the first evidence for common genetic variants influencing female sexual maturation.

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Lukusa, M. T. W., Yang, C.-Y., & Tsai, M. (2024) · Pediatrics & Neonatology · doi:10.1016/j.pedneo.2024.04.012 · Cited by 1
The Genetics of Pubertal Growth and Timing
Cousminer, D. L. (2015) · Työväentutkimus Vuosikirja
Additional file 8 of Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Taschereau, A., Thibeault, K., Allard, C., Juvinao-Quintero, D. L., Perron, P., Lutz, S. M., Bouchard, L., & Hivert, M. (2024) · Figshare · doi:10.6084/m9.figshare.26600713
Additional file 9 of Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Taschereau, A., Thibeault, K., Allard, C., Juvinao-Quintero, D. L., Perron, P., Lutz, S. M., Bouchard, L., & Hivert, M. (2024) · Figshare · doi:10.6084/m9.figshare.26600716
Additional file 3 of Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Taschereau, A., Thibeault, K., Allard, C., Juvinao-Quintero, D. L., Perron, P., Lutz, S. M., Bouchard, L., & Hivert, M. (2024) · Figshare · doi:10.6084/m9.figshare.26600698
Additional file 4 of Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Taschereau, A., Thibeault, K., Allard, C., Juvinao-Quintero, D. L., Perron, P., Lutz, S. M., Bouchard, L., & Hivert, M. (2024) · Figshare · doi:10.6084/m9.figshare.26600701
Additional file 6 of Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Taschereau, A., Thibeault, K., Allard, C., Juvinao-Quintero, D. L., Perron, P., Lutz, S. M., Bouchard, L., & Hivert, M. (2024) · Figshare · doi:10.6084/m9.figshare.26600707
Additional file 2 of Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Taschereau, A., Thibeault, K., Allard, C., Juvinao-Quintero, D. L., Perron, P., Lutz, S. M., Bouchard, L., & Hivert, M. (2024) · Figshare · doi:10.6084/m9.figshare.26600695
Additional file 7 of Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Taschereau, A., Thibeault, K., Allard, C., Juvinao-Quintero, D. L., Perron, P., Lutz, S. M., Bouchard, L., & Hivert, M. (2024) · Figshare · doi:10.6084/m9.figshare.26600710
Additional file 5 of Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Taschereau, A., Thibeault, K., Allard, C., Juvinao-Quintero, D. L., Perron, P., Lutz, S. M., Bouchard, L., & Hivert, M. (2024) · Figshare · doi:10.6084/m9.figshare.26600704
Additional file 1 of Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Taschereau, A., Thibeault, K., Allard, C., Juvinao-Quintero, D. L., Perron, P., Lutz, S. M., Bouchard, L., & Hivert, M. (2024) · Figshare · doi:10.6084/m9.figshare.26600692
let-7 miRNA and lin-46 mRNA are the two essential targets of the LIN28 RNA-binding protein in developmental timingPreprint
Brunner, J., Neagu, A., Gaidatzis, D., Moya, L. J. M., & Großhans, H. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.12.699064
Zfp462 Is a Key Mediator of Osteoblast Differentiation and Might Contribute to Age‐Related Bone Loss
Kim, J., Kim, H. K., Moon, S.-A., Kim, Y., Lee, S., Yu, J., Lee, S. H., Son, W., Kim, J., Baek, I., et al. (2026) · Aging Cell · doi:10.1111/acel.70476
Puberty development: determinants and health impacts
Yang, Y., & Lu, D. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45863-7.00022-6
let-7 miRNA and lin-46 mRNA are essential targets of the LIN28 RNA-binding protein in Caenorhabditis elegans developmental timing regulation
Brunner, J., Neagu, A., Gaidatzis, D., Moya, L. J. M., & Großhans, H. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003892
CYP19A1 variation in healthy children: associations with breast development and pubertal gynecomastia
Groendahl, V. L. R., Ahmed, S. F., Busch, A. S., Hagen, C. P., Petersen, J. H., Johannsen, T. H., Almstrup, K., Frederiksen, H. W., Juul, A., & Aksglæde, L. (2026) · Endocrine Connections · doi:10.1530/ec-26-0182

Authors: Perry, J. R. B., Stolk, L., Franceschini, N., Lunetta, K. L., Zhai, G., McArdle, P. F., Smith, A. V., Aspelund, T., Bandinelli, S., Boerwinkle, E., Cherkas, L., Eiriksdottir, G., Estrada, K., Ferrucci, L., Folsom, A. R., Garcia, M., Gudnason, V., Hofman, A., Karasik, D., Kiel, D. P., Launer, L. J., van Meurs, J., Nalls, M. A., Rivadeneira, F., Shuldiner, A. R., Singleton, A., Soranzo, N., Tanaka, T., Visser, J. A., Weedon, M. N., Wilson, S. G., Zhuang, V., Streeten, E. A., Harris, T. B., Murray, A., Spector, T. D., Demerath, E. W., Uitterlinden, A. G., & Murabito, J. M.
Affiliations: University of Exeter (GB)
Erasmus MC (NL)
University of North Carolina at Chapel Hill (US)
Boston University (US)
King's College London (GB)
University of Maryland, Baltimore (US)
Icelandic Heart Association (IS)
University of Iceland (IS)
Azienda Sanitaria di Firenze (IT)
The University of Texas Health Science Center at Houston (US)
National Institute on Aging (US)
University of Minnesota (US)
National Institutes of Health (US)
Harvard University (US)
The University of Western Australia (AU)
Corresponding author: Uitterlinden, André G
ORCID: Perry, John R B
Franceschini, Nora
Lunetta, Kathryn L
Zhai, Guangju
McArdle, Patrick F
Smith, Albert V
Aspelund, Thor
Bandinelli, Stefania
Boerwinkle, Eric
Estrada, Karol
Ferrucci, Luigi
Folsom, Aaron R
Gudnason, Vilmundur
Karasik, David
Kiel, Douglas P
Launer, Lenore J
Rivadeneira, Fernando
Shuldiner, Alan R
Singleton, Andrew
Soranzo, Nicole
Tanaka, Toshiko
Weedon, Michael N
Wilson, Scott G
Streeten, Elizabeth A
Harris, Tamara B
Murray, Anna
Spector, Tim D
Demerath, Ellen W
Uitterlinden, André G
Murabito, Joanne M
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2009-05-17
Volume: 41
Issue: 6
Pages: 648-650
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng.386
PMC: PMC2942986
OpenAlex: W2081422943
Cited by: 294
References: 16
Citations by year: 2026: 6 · 2025: 3 · 2024: 16 · 2023: 9 · 2022: 8 · 2021: 14 · 2020: 16 · 2019: 14 · 2018: 18 · 2017: 14 · 2016: 16 · 2015: 19 · 2014: 16 · 2013: 39 · 2012: 35
FWCI: 4.04
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
PubMed Central (acceptedVersion)
UWA Profiles and Research Repository (UWA) (submittedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: Wellcome Trust
National Institutes of Health (n01ag12100-57-0-2, n01hc55021-47-0-1, n01hc55020-39-0-0, n01hc55016-37-0-0, n01hc055022-024, n01hc55019-35-0-1, n01hc55018-38-0-1, n01hc25195-41-0-1, n02hl64278-6-0-0, n01hc55015-48-0-1)
National Institute on Aging (N.1‐AG‐1‐2111, N01-AG12100, N01-AG012100, N.1-AG-1-1, R01AR/AG 41398, R21AG032598, U19AG023122, N01 AG-5-0002)
National Heart, Lung, and Blood Institute (N01-HC55022, U01HL72515, N01 HC055016, N01-HC-55018, N01 HC 55020, N01‐HC25195, N01 HC 55019, N01 HC055020, N02 HL064278, N02- HL-64278, N01 HC055018, N01-HC-025195, N01-HC55016, N01 HC055022, U01HL072515, N01 HC055019, N01‐HC‐55015, N01-HC55021, N01 HC055021, N01 HC055015)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072488)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041398)
National Center for Research Resources (M01RR016500, M01RR 16500)
National Institute on Minority Health and Health Disparities (263MD9164, 263MD 821336)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords: age at menarche, female sexual maturation, LIN28B, fukutin, genetic loci, adult height, genetic variants, puberty
MeSH terms: Adolescent, Age Factors, Child, Chromosome Mapping, Chromosomes, Human, Pair 6, Chromosomes, Human, Pair 8, Chromosomes, Human, Pair 9, DNA-Binding Proteins, Female, Humans, Menarche, Sexual Maturation, Genetic Variation, Meta-Analysis as Topic, Body Mass Index, RNA-Binding Proteins, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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Meta-analysis of genome-wide association data identifies two loci influencing age at menarche

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