Genetic variation in LIN28B is associated with the timing of puberty

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