title: Pubertal onset in girls is strongly influenced by genetic variation affecting FSH action.
abstract: Age at pubertal onset varies substantially in healthy girls. Although genetic factors are responsible for more than half of the phenotypic variation, only a small part has been attributed to specific genetic polymorphisms identified so far. Follicle-stimulating hormone (FSH) stimulates ovarian follicle maturation and estradiol synthesis which is responsible for breast development. We assessed the effect of three polymorphisms influencing FSH action on age at breast deveopment in a population-based cohort of 964 healthy girls. Girls homozygous for FSHR -29AA (reduced FSH receptor expression) entered puberty 7.4 (2.5-12.4) months later than carriers of the common variants FSHR -29GG+GA, p = 0.003. To our knowledge, this is the strongest genetic effect on age at pubertal onset in girls published to date.
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Casper P
authors.initials: CP
authors.lastname: Hagen
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Sørensen
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Aksglaede
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Annette
authors.initials: A
authors.lastname: Mouritsen
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Mikkel G
authors.initials: MG
authors.lastname: Mieritz
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Tinggaard
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Christine
authors.initials: C
authors.lastname: Wohlfart-Veje
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Jørgen Holm
authors.initials: JH
authors.lastname: Petersen
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Ewa
authors.initials: E
authors.lastname: Rajpert-De Meyts
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Almstrup
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D002648:Child; D003430:Cross-Sectional Studies; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D011110:Polymorphism, Genetic; D011627:Puberty / Q000097:blood / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011962:Receptors, FSH / Q000235:genetics*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D011962:Receptors, FSH; D004247:DNA