Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche
Abstract
Earlier menarche correlates with shorter adult height and higher childhood body fat. We conducted a genome-wide association study of age at menarche (AAM) on 15,297 Icelandic women. Combined analysis with replication sets from Iceland, Denmark and the Netherlands (N = 10,040) yielded a significant association between rs314280[T] on 6q21, near the LIN28B gene, and AAM (effect = 1.2 months later per allele; P = 1.8 × 10(-14)). A second SNP within the same linkage disequilibrium (LD) block, rs314277, splits rs314280[T] into two haplotypes with different effects (0.9 months and 1.9 months per allele). These variants have been associated with greater adult height. The association with adult height did not account for the association with AAM or vice versa. Other variants, previously associated with height, did not associate significantly with AAM. Given the link between body fat and AAM, we also assessed 11 variants recently associated with higher body mass index (BMI) and 5 of those associated with earlier AAM.
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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 [82]
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 [11]
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 [11]
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- Authors
- Sulem, P., Gudbjartsson, D. F., Rafnar, T., Holm, H., Olafsdottir, E. J., Olafsdottir, G. H., Jonsson, T., Alexandersen, P., Feenstra, B., Boyd, H. A., Aben, K. K., Verbeek, A. L. M., Roeleveld, N., Jonasdottir, A., Styrkarsdottir, U., Steinthorsdottir, V., Karason, A., Stacey, S. N., Gudmundsson, J., Jakobsdottir, M., Thorleifsson, G., Hardarson, G., Gulcher, J., Kong, A., Kiemeney, L. A., Melbye, M., Christiansen, C., Tryggvadottir, L., Thorsteinsdottir, U., & Stefansson, K.
- Affiliations
- deCODE Genetics (Iceland) (IS)
- Center for Clinical & Basic Research (DK)
- Statens Serum Institut (DK)
- Radboud University Nijmegen (NL)
- Nordic Bioscience (Denmark) (DK)
- Corresponding author
- Sulem, Patrick
- ORCID
- Venue
- Nature Genetics
- Published
- 2009-05-17
- Volume
- 41
- Issue
- 6
- Pages
- 734-738
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2085463723
- Cited by
- 219
- References
- 31
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 8 · 2022: 1 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 11 · 2017: 6 · 2016: 14 · 2015: 20 · 2014: 17 · 2013: 31 · 2012: 29
- FWCI
- 30.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Funders
- Radboud Universiteit
- 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, LIN28B, 6q21, genetic variants, adult height, body mass index, fat mass, haplotypes, linkage disequilibrium, Icelandic women
- MeSH terms
- Adipose Tissue, Adult, Aging, Anthropometry, Base Sequence, Body Height, Chromosome Mapping, Chromosomes, Human, Pair 6, Denmark, Female, Humans, Iceland, Menarche, Netherlands, Transcription, Genetic, Genetic Variation, Body Mass Index, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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