Genetic variation in LIN28B is associated with the timing of puberty

KK Ong; CE Elks; S Li; JH Zhao; J Luan; LB Andersen; S A Bingham; S Brage; G Davey Smith; U Ekelund; CJ Gillson; MUB Glaser; J Golding; R Hardy; KT Khaw; D Kuh; R Luben; M Marcus; MA McGeehin; A Ness; K Northstone; SM Ring; C Rubin; MA Sims; K Song; DP Strachan; P Vollenweider; G Waeber; DM Waterworth; A Wong; P Deloukas; I Barroso; V Mooser; RJ Loos; NJ Wareham

doi:10.1038/ng.382

Genetic variation in LIN28B is associated with the timing of puberty

KK Ong, CE Elks, S Li, JH Zhao, J Luan, LB Andersen, S A Bingham, S Brage, G Davey Smith, U Ekelund, CJ Gillson, MUB Glaser, J Golding, R Hardy, KT Khaw, D Kuh, R Luben, M Marcus, MA McGeehin, A NessK Northstone, SM Ring, C Rubin, MA Sims, K Song, DP Strachan, P Vollenweider, G Waeber, DM Waterworth, A Wong, P Deloukas, I Barroso, V Mooser, RJ Loos, NJ Wareham

Research output: Contribution to journal › Article (Academic Journal) › peer-review

255 Citations (Scopus)

Abstract

The timing of puberty is highly variable1. We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 times 10-8). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08–0.16; P = 2.8 times 10-10; combined P = 3.6 times 10-16). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 times 10-7; N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing2, as the first genetic determinant regulating the timing of human pubertal growth and development.

Translated title of the contribution	Genetic variation in LIN28B is associated with the timing of puberty
Original language	English
Pages (from-to)	729-733
Journal	Nature Genetics
Volume	41
DOIs	https://doi.org/10.1038/ng.382
Publication status	Published - 2009

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Publisher: Nature Pub. Co

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Ong, KK., Elks, CE., Li, S., Zhao, JH., Luan, J., Andersen, LB., Bingham, S. A., Brage, S., Davey Smith, G., Ekelund, U., Gillson, CJ., Glaser, MUB., Golding, J., Hardy, R., Khaw, KT., Kuh, D., Luben, R., Marcus, M., McGeehin, MA., ... Wareham, NJ. (2009). Genetic variation in LIN28B is associated with the timing of puberty. Nature Genetics, 41, 729-733. https://doi.org/10.1038/ng.382

Ong, KK ; Elks, CE ; Li, S ; Zhao, JH ; Luan, J ; Andersen, LB ; Bingham, S A ; Brage, S ; Davey Smith, G ; Ekelund, U ; Gillson, CJ ; Glaser, MUB ; Golding, J ; Hardy, R ; Khaw, KT ; Kuh, D ; Luben, R ; Marcus, M ; McGeehin, MA ; Ness, A ; Northstone, K ; Ring, SM ; Rubin, C ; Sims, MA ; Song, K ; Strachan, DP ; Vollenweider, P ; Waeber, G ; Waterworth, DM ; Wong, A ; Deloukas, P ; Barroso, I ; Mooser, V ; Loos, RJ ; Wareham, NJ. / Genetic variation in LIN28B is associated with the timing of puberty. In: Nature Genetics. 2009 ; Vol. 41. pp. 729-733.

@article{ab788a25e5f745f1a2d8ff8f94f9d06c,

title = "Genetic variation in LIN28B is associated with the timing of puberty",

abstract = "The timing of puberty is highly variable1. We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 times 10-8). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08–0.16; P = 2.8 times 10-10; combined P = 3.6 times 10-16). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 times 10-7; N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing2, as the first genetic determinant regulating the timing of human pubertal growth and development.",

author = "KK Ong and CE Elks and S Li and JH Zhao and J Luan and LB Andersen and Bingham, {S A} and S Brage and {Davey Smith}, G and U Ekelund and CJ Gillson and MUB Glaser and J Golding and R Hardy and KT Khaw and D Kuh and R Luben and M Marcus and MA McGeehin and A Ness and K Northstone and SM Ring and C Rubin and MA Sims and K Song and DP Strachan and P Vollenweider and G Waeber and DM Waterworth and A Wong and P Deloukas and I Barroso and V Mooser and RJ Loos and NJ Wareham",

note = "Publisher: Nature Pub. Co",

year = "2009",

doi = "10.1038/ng.382",

language = "English",

volume = "41",

pages = "729--733",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Springer Nature",

}

Ong, KK, Elks, CE, Li, S, Zhao, JH, Luan, J, Andersen, LB, Bingham, SA, Brage, S, Davey Smith, G, Ekelund, U, Gillson, CJ, Glaser, MUB , Golding, J, Hardy, R, Khaw, KT, Kuh, D, Luben, R, Marcus, M, McGeehin, MA, Ness, A , Northstone, K , Ring, SM, Rubin, C, Sims, MA, Song, K, Strachan, DP, Vollenweider, P, Waeber, G, Waterworth, DM, Wong, A, Deloukas, P, Barroso, I, Mooser, V, Loos, RJ & Wareham, NJ 2009, 'Genetic variation in LIN28B is associated with the timing of puberty', Nature Genetics, vol. 41, pp. 729-733. https://doi.org/10.1038/ng.382

Genetic variation in LIN28B is associated with the timing of puberty. / Ong, KK; Elks, CE; Li, S; Zhao, JH; Luan, J; Andersen, LB; Bingham, S A; Brage, S; Davey Smith, G; Ekelund, U; Gillson, CJ; Glaser, MUB ; Golding, J; Hardy, R; Khaw, KT; Kuh, D; Luben, R; Marcus, M; McGeehin, MA; Ness, A ; Northstone, K ; Ring, SM; Rubin, C; Sims, MA; Song, K; Strachan, DP; Vollenweider, P; Waeber, G; Waterworth, DM; Wong, A; Deloukas, P; Barroso, I; Mooser, V; Loos, RJ; Wareham, NJ.

In: Nature Genetics, Vol. 41, 2009, p. 729-733.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Genetic variation in LIN28B is associated with the timing of puberty

AU - Ong, KK

AU - Elks, CE

AU - Li, S

AU - Zhao, JH

AU - Luan, J

AU - Andersen, LB

AU - Bingham, S A

AU - Brage, S

AU - Davey Smith, G

AU - Ekelund, U

AU - Gillson, CJ

AU - Glaser, MUB

AU - Golding, J

AU - Hardy, R

AU - Khaw, KT

AU - Kuh, D

AU - Luben, R

AU - Marcus, M

AU - McGeehin, MA

AU - Ness, A

AU - Northstone, K

AU - Ring, SM

AU - Rubin, C

AU - Sims, MA

AU - Song, K

AU - Strachan, DP

AU - Vollenweider, P

AU - Waeber, G

AU - Waterworth, DM

AU - Wong, A

AU - Deloukas, P

AU - Barroso, I

AU - Mooser, V

AU - Loos, RJ

AU - Wareham, NJ

N1 - Publisher: Nature Pub. Co

PY - 2009

Y1 - 2009

N2 - The timing of puberty is highly variable1. We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 times 10-8). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08–0.16; P = 2.8 times 10-10; combined P = 3.6 times 10-16). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 times 10-7; N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing2, as the first genetic determinant regulating the timing of human pubertal growth and development.

AB - The timing of puberty is highly variable1. We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 times 10-8). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08–0.16; P = 2.8 times 10-10; combined P = 3.6 times 10-16). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 times 10-7; N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing2, as the first genetic determinant regulating the timing of human pubertal growth and development.

U2 - 10.1038/ng.382

DO - 10.1038/ng.382

M3 - Article (Academic Journal)

C2 - 19448623

VL - 41

SP - 729

EP - 733

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -