Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche

• Published in: Nature genetics Vol. 41; no. 6; pp. 734 - 738
• Main Authors: Sulem, Patrick, Stefansson, Kari, Gudbjartsson, Daniel F, Rafnar, Thorunn, Holm, Hilma, Olafsdottir, Elinborg J, Olafsdottir, Gudridur H, Jonsson, Thorvaldur, Alexandersen, Peter, Feenstra, Bjarke, Boyd, Heather A, Aben, Katja K, Verbeek, Andre L M, Roeleveld, Nel, Jonasdottir, Aslaug, Styrkarsdottir, Unnur, Steinthorsdottir, Valgerdur, Karason, Ari, Stacey, Simon N, Gudmundsson, Julius, Jakobsdottir, Margret, Thorleifsson, Gudmar, Hardarson, Gudmundur, Gulcher, Jeffrey, Kong, Augustine, Kiemeney, Lambertus A, Melbye, Mads, Christiansen, Claus, Tryggvadottir, Laufey, Thorsteinsdottir, Unnur
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2009; Nature Publishing Group
• Subjects: Adipose Tissue - anatomy & histology; Adipose tissues; Adult; Aging - physiology; Agriculture; Animal Genetics and Genomics; Anthropometry - methods; Base Sequence; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Body Height - genetics; Body Mass Index; Cancer Research; Chromosome Mapping; Chromosomes, Human, Pair 6 - genetics; Classical genetics, quantitative genetics, hybrids; Denmark; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Genes; Genetic aspects; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomics; Haplotypes; Human Genetics; Humans; Iceland; Industrialized nations; letter; Menarche; Menarche - genetics; Menstruation; Methods, theories and miscellaneous; Netherlands; Physiological aspects; Polymorphism, Single Nucleotide - genetics; Risk factors; Transcription, Genetic; Denmark; Netherlands; Iceland; Genetic mapping; Variant; Identification; Association; Age
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.383

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.