Meta-analysis of genome-wide association data identifies two loci influencing age at menarche
Open accessAbstract
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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In 2009, genome-wide association studies identified an association between the locus 6q21 (in or near the LIN28B gene) and age at menarche and height.
“In 2009, genome-wide association studies identified an association between the locus 6q21 (in or near the LIN28B gene) with age at menarche and height.81–84”
From Pubertal development and regulation (2016) · cites this paper as [81]
A second menarche locus was identified in an intergenic region at 9q31.2.
“A second menarche locus was identified in an intergenic region at 9q31.28,10.”
From Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies (2010) · cites this paper as [10]
Common variants in LIN28B were associated with age at menarche in four independent genome-wide association studies.
“common variants in LIN28B were associated with age at menarche in four independent genome-wide association studies (GWAS)8–11”
From Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies (2010) · cites this paper as [10]
Previous studies comprising up to 17,510 women had detected only one or two genome-wide significant signals.
“Previous studies comprising up to 17,510 women had detected only one or two genome-wide significant signals8–11.”
From Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies (2010) · cites this paper as [10]
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Self-citation
- 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
- Published
- 2009-05-17
- Volume
- 41
- Issue
- 6
- Pages
- 648-650
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- 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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