Genome-wide association studies identify loci associated with age at menarche and age at natural menopause
Open accessAbstract
Age at menarche and age at natural menopause are associated with causes of substantial morbidity and mortality such as breast cancer and cardiovascular disease. We conducted a joint analysis of two genome-wide association studies of these two traits in a total of 17,438 women from the Nurses' Health Study (NHS, N = 2,287) and the Women's Genome Health Study (WGHS, N = 15,151). For age at menarche, we identified ten associated SNPs (P = 1 × 10(-7)-3 × 10(-13)) clustered at 6q21 (in or near the gene LIN28B) and 9q31.2 (in an intergenic region). For age at natural menopause, we identified 13 associated SNPs (P = 1 × 10(-7)-1 × 10(-21)) clustered at 20p12.3 (in the gene MCM8), 19q13.42 (in or near the gene BRSK1), 5q35.2 (in or near genes UIMC1 and HK3) and 6p24.2 (in the gene SYCP2L). These newly identified loci might expand understanding of the biological pathways regulating these two traits.
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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 [83]
The two known loci together explained only 0.6% of the variance in age at menarche.
“These two loci together explained only 0.6% of the variance in age at menarche8.”
From Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies (2010) · cites this paper as [8]
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 [8]
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 [8]
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 [8]
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- Authors
- He, C., Kraft, P., Chen, C., Buring, J. E., Paré, G., Hankinson, S. E., Chanock, S. J., Ridker, P. M., Hunter, D. J., & Chasman, D. I.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- National Institutes of Health (US)
- Broad Institute (US)
- Corresponding author
- He, Chunyan
- ORCID
- Venue
- Nature Genetics
- Published
- 2009-05-17
- Volume
- 41
- Issue
- 6
- Pages
- 724-728
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2888798
- OpenAlex
- W2136326352
- Cited by
- 379
- References
- 30
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 16 · 2023: 15 · 2022: 13 · 2021: 16 · 2020: 13 · 2019: 23 · 2018: 27 · 2017: 16 · 2016: 22 · 2015: 35 · 2014: 22 · 2013: 45 · 2012: 38
- FWCI
- 20.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Amgen
- Fondation Leducq
- National Institutes of Health (5r01hl043851-10)
- National Heart, Lung, and Blood Institute (HL043851, R01‐HL043851, U19HL069757, U01HL069757, HL 69757)
- National Cancer Institute (R01CA040356, CA-40356, CA98233, CA 047988, U01 CA 98233, U01CA098233, R01CA047988)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- age at menarche, age at natural menopause, genetic loci, single nucleotide polymorphisms, LIN28B, MCM8, HK3, female reproductive aging, breast cancer risk, cardiovascular risk, Nurses' Health Study
- MeSH terms
- Age Factors, Chromosome Mapping, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 20, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Chromosomes, Human, Pair 9, Female, Humans, Menarche, Menopause, Cohort Studies, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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