title: Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche.
abstract: Earlier menarche correlates with shorter adult height and higher childhood body fat. We conducted a genome-wide association study of age at menarche (AAM) on 15,297 Icelandic women. Combined analysis with replication sets from Iceland, Denmark and the Netherlands (N = 10,040) yielded a significant association between rs314280[T] on 6q21, near the LIN28B gene, and AAM (effect = 1.2 months later per allele; P = 1.8 × 10(-14)). A second SNP within the same linkage disequilibrium (LD) block, rs314277, splits rs314280[T] into two haplotypes with different effects (0.9 months and 1.9 months per allele). These variants have been associated with greater adult height. The association with adult height did not account for the association with AAM or vice versa. Other variants, previously associated with height, did not associate significantly with AAM. Given the link between body fat and AAM, we also assessed 11 variants recently associated with higher body mass index (BMI) and 5 of those associated with earlier AAM.
authors.affiliation: deCODE Genetics, Reykjavik, Iceland. patrick.sulem@decode.is
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.forename: Elinborg J
authors.initials: EJ
authors.lastname: Olafsdottir
authors.forename: Gudridur H
authors.initials: GH
authors.lastname: Olafsdottir
authors.forename: Thorvaldur
authors.initials: T
authors.lastname: Jonsson
authors.forename: Peter
authors.initials: P
authors.lastname: Alexandersen
authors.forename: Bjarke
authors.initials: B
authors.lastname: Feenstra
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boyd
authors.forename: Katja K
authors.initials: KK
authors.lastname: Aben
authors.forename: Andre L M
authors.initials: AL
authors.lastname: Verbeek
authors.forename: Nel
authors.initials: N
authors.lastname: Roeleveld
authors.forename: Aslaug
authors.initials: A
authors.lastname: Jonasdottir
authors.forename: Unnur
authors.initials: U
authors.lastname: Styrkarsdottir
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Steinthorsdottir
authors.forename: Ari
authors.initials: A
authors.lastname: Karason
authors.forename: Simon N
authors.initials: SN
authors.lastname: Stacey
authors.forename: Julius
authors.initials: J
authors.lastname: Gudmundsson
authors.forename: Margret
authors.initials: M
authors.lastname: Jakobsdottir
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Hardarson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gulcher
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Laufey
authors.initials: L
authors.lastname: Tryggvadottir
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D000375:Aging / Q000502:physiology*; D000886:Anthropometry / Q000379:methods; D001483:Base Sequence; D001827:Body Height / Q000235:genetics; D015992:Body Mass Index; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003718:Denmark; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007055:Iceland; D008572:Menarche / Q000235:genetics*; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014158:Transcription, Genetic