Loci at chromosomes 13, 19 and 20 influence age at natural menopause

We conducted a genome-wide association study for age at natural menopause in 2,979 European women and identified six SNPs in three loci associated with age at natural menopause: chromosome 19q13.4 (rs1172822; -0.4 year per T allele (39%); P = 6.3 × 10−11), chromosome 20p12.3 (rs236114; +0.5 year per...

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Published inNature genetics Vol. 41; no. 6; pp. 645 - 647
Main Authors Stolk, Lisette, Deloukas, Panos, Laven, Joop S E, van Meurs, Joyce B J, Verbiest, Michael M P J, Witteman, Jacqueline, Estrada, Karol, Uitterlinden, André G, Pop, Victor J M, Cherkas, Lynn, Pols, Huibert A P, Lips, Paul, Lebrun, Corinne E I, Soranzo, Nicole, de Keyzer, Jules J, van der Schouw, Yvonne T, Hofman, Albert, Williams, Frances M, Grobbee, Diederick E, Rivadeneira, Fernando, Visser, Jenny A, Zhai, Guangju, Spector, Tim D
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.06.2009
Nature Publishing Group
Subjects
Age Factors
Agriculture
Animal Genetics and Genomics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - genetics
brief-communication
Cancer Research
Cardiovascular diseases
Cardiovascular Diseases - genetics
Chromosomes
Chromosomes, Human, Pair 13 - genetics
Chromosomes, Human, Pair 19 - genetics
Chromosomes, Human, Pair 20 - genetics
Female
Fundamental and applied biological sciences. Psychology
Gene Function
Gene loci
Genes
Genetic aspects
Genetic variance
Genetic Variation
Genetics
Genetics of eukaryotes. Biological and molecular evolution
Genome-Wide Association Study
Health aspects
Human Genetics
Humans
Medical research
Menopause
Menopause - genetics
Meta-analysis
Meta-Analysis as Topic
Middle Aged
Odds Ratio
Osteoporosis
Osteoporosis - genetics
Physiological aspects
Polymorphism, Single Nucleotide
Risk Factors
Single nucleotide polymorphisms
Studies
Twin Studies as Topic
White People - genetics
United Kingdom
Netherlands
Chromosome 19
Chromosome 13
Locus
Menopause
Age
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Summary:We conducted a genome-wide association study for age at natural menopause in 2,979 European women and identified six SNPs in three loci associated with age at natural menopause: chromosome 19q13.4 (rs1172822; -0.4 year per T allele (39%); P = 6.3 × 10−11), chromosome 20p12.3 (rs236114; +0.5 year per A allele (21%); P = 9.7 × 10−11) and chromosome 13q34 (rs7333181; +0.5 year per A allele (12%); P = 2.5 × 10−8). These common genetic variants regulate timing of ovarian aging, an important risk factor for breast cancer, osteoporosis and cardiovascular disease.
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AUTHOR CONTRIBUTIONS
These authors contributed equally to this work.
L.S., G.Z., T.D.S. and A.G.U. designed the study. L.S. and M.M.P.J.V. did the genotyping of the replication studies. P.D. and N.S. did the genotyping for the TwinsUK study. N.S. did the quality control for the TwinsUK data. L.S., G.Z., J.B.J.v.M. and K.E. did the statistical analyses. L.S., G.Z., J.B.J.v.M., J.A.V., F.R., J.S.E.L., T.D.S. and A.G.U. helped with the interpretation of the results. L.S., G.Z., J.B.J.v.M., J.A.V., F.R., T.D.S. and A.G.U. prepared the manuscript and the revision of the manuscript. F.M.W., A.H. and H.A.P.P. critically revised the manuscript. A.H., J.W., H.A.P.P. and A.G.U. were involved in the sample and phenotype collection of the Rotterdam Study. F.M.W. and L.C. were involved in the phenotype collection of the TwinsUK Study. J.J.d.K., V.J.M.P., P.L., C.E.I.L., Y.T.v.d.S. and D.E.G. were involved in the sample and data collection of the replication studies.
ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/ng.387