Genetic variation in LIN28B is associated with the timing of puberty

Kenneth H. Davis; R. E. Folsom; F. Ivy Carroll; Phillip C. Cooley; Lyle M. Retzlaff; Michael F. Weeks; H. Koo; Herbert H. Seltzman; E. Pellizzari; Deborah W. McFadden; Roger D. Austin; Martin B. Lee; Judith T. Lynch; Debra M. Fleischmann; Carol Place; Stephen D. Cooper; Rick L. Williams; Lillie B. Barber; Doris J. Rouse; Ivey A. McDaniel; Charlotte O. Scheper; Paul Kizakevich; Donna M. Jewell; Marion E. Deerhake; Cora B. Parker; Eugene P. Brantly; Phyllis D. Elkins; Patricia A. Cunningham; Robert S. Truesdale; Sara C. Wheeless; Robert M. Bray; Cynthia A. Salmons; Gary B. Howe; Coleen M. Northeim; Susan K. Myers; Gordon M. Cressman; Josephine A. Mauskopf; Tim J. Gabel; Luis Arturo Crouch; Celia D. Keller; Lisa E. Packer; Pamela B. Lamb; Keith White Little; Nathaniel F. Rodman; M. Owen; James P. Hayes; Daniel L. Winfield; Deborah A. Gibbs; Janice E. Kelly-Reid; Wayne G. Winstead; Cindy O. McClintock; Terrence K. Pierson; Johnny R. Albritton; Sherry L. Black; Jeffrey B. Coburn; Joe B. Simpson; Ed E. Rickman; James T. Hanley; R. Suresh; Barbara L. Kroner; K. Heller; James C. Blake; Barri B. Burrus; Anthony C. Clayton; Donna S. Womack; S. Mascarella; Scott A. Guthrie; Sheryl C. Cates; Albert D. Bethke; Suson F. VonLehmden; Kathryn L. Dowd; Daniel J. Pratt; Lisa J. McQuay; Matthew A. Koch; Jonathan T. Ennis; Robert A. Zerbonia; Nick L. Kinsey; Susan H. Kinsey; Christopher P. Carson; J. Newsome; S. Keesling; James A. O'Rourke; Kathryn R. Batts; Craig R. Hollingsworth; Priya Suresh; Joseph Wendell Wilson; Vorapranee Wickelgren; E. Andrew Jessup; Diana S. Goss; Sheri E. Fehnel; Gayle S. Bieler; Donna P. Coleman; R. Crawford; Jeanne Ann Snodgrass; Nellie I. Hansen; Michelle Lang; Deirdre M. Mladsi; Gary A. Zarkin; Rachel A. Caspar; Carol L. Woodell; KK Ong; CE Elks; Sheping Li; JH Zhao; J Luan; LB Andersen; SA Bingham; S Brage; GD Smith; U Ekelund; CJ Gillson; B Glaser; J Golding; R Hardy; KT Khaw; D Kuh; R Luben; M Marcus; Michael McGeehin; AR 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

Genetic variation in LIN28B is associated with the timing of puberty

Ong, KK., Elks, CE., Li, S., Zhao, JH., Luan, J., Andersen, LB., Bingham, SA., Brage, S., Smith, GD., Ekelund, U., Gillson, CJ., Glaser, B., Golding, J., Hardy, R., Khaw, KT., Kuh, D., Luben, R., Marcus, M., McGeehin, M., ... Wareham, NJ. (2009). Genetic variation in LIN28B is associated with the timing of puberty. Nature Genetics, 41(6), 729-733.

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Abstract

The timing of puberty is highly variable. 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) +AD0- 0.33, P +AD0- 1.5 x 10(-8)). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95+ACU- CI +AD0- 0.08-0.16+ADs- P +AD0- 2.8 x 10(-10)+ADs- combined P +AD0- 3.6 x 10(-16)). This allele was also associated with earlier breast development in girls (P +AD0- 0.001+ADs- N +AD0- 4,271)+ADs- earlier voice breaking (P +AD0- 0.006, N +AD0- 1,026) and more advanced pubic hair development in boys (P +AD0- 0.01+ADs- N +AD0- 4,588)+ADs- a faster tempo of height growth in girls (P +AD0- 0.00008+ADs- N +AD0- 4,271) and boys (P +AD0- 0.03+ADs- N +AD0- 4,588)+ADs- and shorter adult height in women (P +AD0- 3.6 x 10(-7)+ADs- N +AD0- 17,274) and men (P +AD0- 0.006+ADs- N +AD0- 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing, as the first genetic determinant regulating the timing of human pubertal growth and development