Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche.
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.
Sulem
Patrick
P
deCODE Genetics, Reykjavik, Iceland. patrick.sulem@decode.is
Gudbjartsson
Daniel F
DF
Rafnar
Thorunn
T
Holm
Hilma
H
Olafsdottir
Elinborg J
EJ
Olafsdottir
Gudridur H
GH
Jonsson
Thorvaldur
T
Alexandersen
Peter
P
Feenstra
Bjarke
B
Boyd
Heather A
HA
Aben
Katja K
KK
Verbeek
Andre L M
AL
Roeleveld
Nel
N
Jonasdottir
Aslaug
A
Styrkarsdottir
Unnur
U
Steinthorsdottir
Valgerdur
V
Karason
Ari
A
Stacey
Simon N
SN
Gudmundsson
Julius
J
Jakobsdottir
Margret
M
Thorleifsson
Gudmar
G
Hardarson
Gudmundur
G
Gulcher
Jeffrey
J
Kong
Augustine
A
Kiemeney
Lambertus A
LA
Melbye
Mads
M
Christiansen
Claus
C
Tryggvadottir
Laufey
L
Thorsteinsdottir
Unnur
U
Stefansson
Kari
K
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