Distinct Variants at LIN28B Influence Growth in Height from Birth to Adulthood
Open accessAbstract
We have studied the largely unknown genetic underpinnings of height growth by using a unique resource of longitudinal childhood height data available in Finnish population cohorts. After applying GWAS mapping of potential genes influencing pubertal height growth followed by further characterization of the genetic effects on complete postnatal growth trajectories, we have identified strong association between variants near LIN28B and pubertal growth (rs7759938; female p = 4.0 x 10(-9), male p = 1.5 x 10(-4), combined p = 5.0 x 10(-11), n = 5038). Analysis of growth during early puberty confirmed an effect on the timing of the growth spurt. Correlated SNPs have previously been implicated as influencing both adult stature and age at menarche, the same alleles associating with taller height and later age of menarche in other studies as with later pubertal growth here. Additionally, a partially correlated LIN28B SNP, rs314277, has been associated previously with final height. Testing both rs7759938 and rs314277 (pairwise r(2) = 0.29) for independent effects on postnatal growth in 8903 subjects indicated that the pubertal timing-associated marker rs7759938 affects prepubertal growth in females (p = 7 x 10(-5)) and final height in males (p = 5 x 10(-4)), whereas rs314277 has sex-specific effects on growth (p for interaction = 0.005) that were distinct from those observed at rs7759938. In conclusion, partially correlated variants at LIN28B tag distinctive, complex, and sex-specific height-growth-regulating effects, influencing the entire period of postnatal growth. These findings imply a critical role for LIN28B in the regulation of human growth.
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The known menarche locus in LIN28B was shown to also influence the onset of breast development in girls, the timing of pubic hair development and voice breaking in boys, and the timing of the pubertal growth spurt in both boys and girls.
“The known menarche locus in LIN28B was shown to also influence the onset of breast development in girls, the timing of pubic hair development and voice breaking in boys9, and the timing of the pubertal growth spurt in both boys and girls41.”
From Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies (2010) · cites this paper as [41]
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Self-citation
- Authors
- Widén, E., Ripatti, S., Cousminer, D. L., Surakka, I., Lappalainen, T., Järvelin, M.-R., Eriksson, J. G., Raitakari, O., Salomaa, V., Sovio, U., Hartikainen, A.-L., Pouta, A., McCarthy, M. I., Osmond, C., Kajantie, E., Lehtimäki, T., Viikari, J., Kähönen, M., Tyler-Smith, C., Freimer, N., Hirschhorn, J. N., Peltonen, L., & Palotie, A.
- Affiliations
- University of Helsinki (FI)
- University of Geneva (CH)
- Imperial College London (GB)
- University of Turku (FI)
- Finnish Institute for Health and Welfare (FI)
- University of Oulu (FI)
- Centre for Human Genetics (GB)
- University of Southampton (GB)
- Tampere University Hospital (FI)
- University of California, Los Angeles (US)
- Broad Institute (US)
- Corresponding author
- Widén, Elisabeth
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 86
- Issue
- 5
- Pages
- 773-782
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2869010
- OpenAlex
- W1981190999
- Cited by
- 88
- References
- 41
- Citations by year
- 2025: 1 · 2024: 8 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 8 · 2015: 6 · 2014: 6 · 2013: 11 · 2012: 14
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Wellcome Trust (89061/Z/09/Z, WT089062)
- 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 › Growth Hormone and Insulin-like Growth Factors
- Keywords
- LIN28B, height growth, pubertal growth, adult height, age at menarche, sex-specific genetic effects
- MeSH terms
- Adolescent, Adult, Body Height, DNA-Binding Proteins, Female, Growth, Humans, Infant, Newborn, Male, Menarche, RNA-Binding Proteins, Polymorphism, Single Nucleotide, White People
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