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 in | Nature genetics Vol. 41; no. 6; pp. 645 - 647 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.06.2009
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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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| AbstractList | André Uitterlinden and colleagues report a genome-wide association study for age at natural menopause, from the Rotterdam Study and TwinsUK, with replication in additional cohorts. They report three loci associated with age at natural menopause, which is a known risk factor for several cancers, osteoporosis and cardiovascular disease.
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. 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. 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 19g13.4 (rsl172822; -0.4 year per T allele (39%); P= 6.3 x 10-11), chromosome 20p12.3 (rs236114; +0.5 year per A allele (21 %); P = 9.7 x [10.sup.-11]) and chromosome 13834 (rs7333181; +0.5 year per A allele (12%); P = 2.5 x [10.sup.-8]). These common genetic variants regulate timing of ovarian aging, an important risk factor for breast cancer, osteoporosis and cardiovascular disease. 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. 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^sup -11^), chromosome 20p12.3 (rs236114; +0.5 year per A allele (21%); P = 9.7 × 10^sup -11^) and chromosome 13q34 (rs7333181; +0.5 year per A allele (12%); P = 2.5 × 10^sup -8^). These common genetic variants regulate timing of ovarian aging, an important risk factor for breast cancer, osteoporosis and cardiovascular disease. [PUBLICATION ABSTRACT] 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.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. 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. 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 [math] 10 super(-11)), chromosome 20p12.3 (rs236114; +0.5 year per A allele (21%); P = 9.7 [math] 10 super(-11)) and chromosome 13q34 (rs7333181; +0.5 year per A allele (12%); P = 2.5 [math] 10 super(-8)). These common genetic variants regulate timing of ovarian aging, an important risk factor for breast cancer, osteoporosis and cardiovascular disease. |
| Audience | Academic |
| Author | Pols, Huibert A P Verbiest, Michael M P J van Meurs, Joyce B J Uitterlinden, André G Deloukas, Panos Estrada, Karol Hofman, Albert van der Schouw, Yvonne T Lebrun, Corinne E I Witteman, Jacqueline Pop, Victor J M Lips, Paul Laven, Joop S E Cherkas, Lynn Spector, Tim D de Keyzer, Jules J Grobbee, Diederick E Stolk, Lisette Zhai, Guangju Rivadeneira, Fernando Visser, Jenny A Williams, Frances M Soranzo, Nicole |
| AuthorAffiliation | 10 Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, The Netherlands 4 Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK 5 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK 7 Department of Clinical Health Psychology, University of Tilburg, Tilburg, The Netherlands 1 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands 6 Research Unit, Diagnostic Center Eindhoven, Eindhoven, The Netherlands 9 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands 3 The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam, The Netherlands 2 Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands 8 Department of Internal Medicine, Endocrine Section, and EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands |
| AuthorAffiliation_xml | – name: 4 Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK – name: 1 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands – name: 5 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK – name: 10 Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, The Netherlands – name: 7 Department of Clinical Health Psychology, University of Tilburg, Tilburg, The Netherlands – name: 8 Department of Internal Medicine, Endocrine Section, and EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands – name: 9 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands – name: 2 Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands – name: 3 The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam, The Netherlands – name: 6 Research Unit, Diagnostic Center Eindhoven, Eindhoven, The Netherlands |
| Author_xml | – givenname: Lisette surname: Stolk fullname: Stolk, Lisette organization: Departments of Internal Medicine, Erasmus MC Department of Epidemiology, Erasmus MC The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA) – givenname: Panos surname: Deloukas fullname: Deloukas, Panos organization: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus – givenname: Joop S E surname: Laven fullname: Laven, Joop S E organization: Department of Obstetrics and Gynaecology, Erasmus MC – givenname: Joyce B J surname: van Meurs fullname: van Meurs, Joyce B J organization: Departments of Internal Medicine, Erasmus MC The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA) – givenname: Michael M P J surname: Verbiest fullname: Verbiest, Michael M P J organization: Departments of Internal Medicine, Erasmus MC – givenname: Jacqueline surname: Witteman fullname: Witteman, Jacqueline organization: Department of Epidemiology, Erasmus MC The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA) – givenname: Karol surname: Estrada fullname: Estrada, Karol organization: Departments of Internal Medicine, Erasmus MC – givenname: André G surname: Uitterlinden fullname: Uitterlinden, André G organization: Departments of Internal Medicine, Erasmus MC Department of Epidemiology, Erasmus MC The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA) – givenname: Victor J M surname: Pop fullname: Pop, Victor J M organization: Department of Clinical Health Psychology, University of Tilburg – givenname: Lynn surname: Cherkas fullname: Cherkas, Lynn organization: Department of Twin Research and Genetic Epidemiology, King's College London – givenname: Huibert A P surname: Pols fullname: Pols, Huibert A P organization: Departments of Internal Medicine, Erasmus MC – givenname: Paul surname: Lips fullname: Lips, Paul organization: Department of Internal Medicine, Endocrine Section, and EMGO Institute, VU University Medical Center – givenname: Corinne E I surname: Lebrun fullname: Lebrun, Corinne E I organization: Departments of Internal Medicine, Erasmus MC Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht – givenname: Nicole surname: Soranzo fullname: Soranzo, Nicole organization: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus – givenname: Jules J surname: de Keyzer fullname: de Keyzer, Jules J organization: Research Unit, Diagnostic Center Eindhoven – givenname: Yvonne T surname: van der Schouw fullname: van der Schouw, Yvonne T organization: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht – givenname: Albert surname: Hofman fullname: Hofman, Albert organization: Department of Epidemiology, Erasmus MC The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA) – givenname: Frances M surname: Williams fullname: Williams, Frances M organization: Department of Twin Research and Genetic Epidemiology, King's College London – givenname: Diederick E surname: Grobbee fullname: Grobbee, Diederick E organization: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht – givenname: Fernando surname: Rivadeneira fullname: Rivadeneira, Fernando organization: Departments of Internal Medicine, Erasmus MC Department of Epidemiology, Erasmus MC – givenname: Jenny A surname: Visser fullname: Visser, Jenny A organization: Departments of Internal Medicine, Erasmus MC – givenname: Guangju surname: Zhai fullname: Zhai, Guangju organization: Department of Twin Research and Genetic Epidemiology, King's College London – givenname: Tim D surname: Spector fullname: Spector, Tim D organization: Department of Twin Research and Genetic Epidemiology, King's College London |
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| ContentType | Journal Article |
| Copyright | Springer Nature America, Inc. 2009 2009 INIST-CNRS COPYRIGHT 2009 Nature Publishing Group Copyright Nature Publishing Group Jun 2009 2009 Nature America, Inc. All rights reserved. 2009 |
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| DOI | 10.1038/ng.387 |
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| Keywords | Chromosome 19 Chromosome 13 Locus Menopause Age |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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. |
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| References | Burger, H.G. (b1) 1996; 10 te Velde, E.R. (b2) 1998; 30 van Asselt, K.M. (b5) 2004; 82 Hofman, A. (b9) 2007; 22 Kok, H.S. (b7) 2005; 20 Snieder, H. (b4) 1998; 83 McCarthy, M.I. (b8) 2008; 9 Purcell, S. (b10) 2007; 81 Weel, A.E. (b6) 1999; 84 Murabito, J.M. (b3) 2005; 90 van AsseltKMFertil. Steril2004821348135110.1016/j.fertnstert.2004.04.047 MurabitoJMJ. Clin. Endocrinol. Metab.200590342734301:CAS:528:DC%2BD2MXkvFClt7o%3D10.1210/jc.2005-0181 te VeldeERMaturitas1998301191251:STN:280:DyaK1M%2FovFSksA%3D%3D10.1016/S0378-5122(98)00067-X KokHSHum. Reprod.2005205365421:CAS:528:DC%2BD2MXovVyluw%3D%3D10.1093/humrep/deh600 WeelAEJ. Clin. Endocrinol. Metab.199984314631501:CAS:528:DyaK1MXlvVGksLg%3D10487678 McCarthyMINat. Rev. Genet.200893563691:CAS:528:DC%2BD1cXkvVOhs7Y%3D10.1038/nrg2344 SniederHJ. Clin. Endocrinol. Metab.199883187518801:CAS:528:DyaK1cXjslCgtLw%3D9626112 BurgerHGBaillieres Clin. Obstet. Gynaecol.1996103473591:STN:280:DyaK2s%2FosFyitg%3D%3D10.1016/S0950-3552(96)80019-8 PurcellSAm. J. Hum. Genet.2007815595751:CAS:528:DC%2BD2sXhtVSqurrL10.1086/519795 HofmanAEur. J. Epidemiol.20072281982910.1007/s10654-007-9199-x 19471299 - Nat Genet. 2009 Jun;41(6):637-8. doi: 10.1038/ng0609-637 KM van Asselt (BFng387_CR5) 2004; 82 JM Murabito (BFng387_CR3) 2005; 90 A Hofman (BFng387_CR9) 2007; 22 ER te Velde (BFng387_CR2) 1998; 30 AE Weel (BFng387_CR6) 1999; 84 MI McCarthy (BFng387_CR8) 2008; 9 HG Burger (BFng387_CR1) 1996; 10 S Purcell (BFng387_CR10) 2007; 81 H Snieder (BFng387_CR4) 1998; 83 HS Kok (BFng387_CR7) 2005; 20 |
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| Snippet | 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... André Uitterlinden and colleagues report a genome-wide association study for age at natural menopause, from the Rotterdam Study and TwinsUK, with replication... |
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| SubjectTerms | 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 |
| Title | Loci at chromosomes 13, 19 and 20 influence age at natural menopause |
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