Genome-wide association studies identify loci associated with age at menarche and age at natural menopause.
paper
Cited
Public
- Authors
- He, Chunyan; Kraft, Peter; Chen, Constance; Buring, Julie E; ParΓ©, Guillaume; Hankinson, Susan E; Chanock, Stephen J; Ridker, Paul M; Hunter, David J; Chasman, Daniel I
- Year
- 2009
- Journal
- Nature genetics
- PMID
- 19448621
- DOI
- 10.1038/ng.385
- PMCID
- PMC2888798
Age at menarche and age at natural menopause are associated with causes of substantial morbidity and mortality such as breast cancer and cardiovascular disease. We conducted a joint analysis of two genome-wide association studies of these two traits in a total of 17,438 women from the Nurses' Health Study (NHS, N = 2,287) and the Women's Genome Health Study (WGHS, N = 15,151). For age at menarche, we identified ten associated SNPs (P = 1 Γ 10(-7)-3 Γ 10(-13)) clustered at 6q21 (in or near the gene LIN28B) and 9q31.2 (in an intergenic region). For age at natural menopause, we identified 13 associated SNPs (P = 1 Γ 10(-7)-1 Γ 10(-21)) clustered at 20p12.3 (in the gene MCM8), 19q13.42 (in or near the gene BRSK1), 5q35.2 (in or near genes UIMC1 and HK3) and 6p24.2 (in the gene SYCP2L). These newly identified loci might expand understanding of the biological pathways regulating these two traits.
Manhattan plots for 317,759 single-SNP tests of association in joint analysis with age at menarche (a) and age at natural menopause (b) by SNP position along chromosome. The dotted lines indicate the P value of 1Γ10-7 (genome wide significance level).
Regional association analyses for age at menarche (a, b) and age at natural menopause (c, d, e, f) in joint analysis. The upper panels show the recombination rate for these regions estimated from HapMap data and P values for association testing from the joint analysis of two GWA studies in the NHS and the WHS, covering most strongly associated SNPs and approximately 50kb upstream and 50kb downstream. The lower panels show estimates of the square of the correlation coefficient (r2) calculated for each pairwise comparison of SNPs. The r2 values are color coded according to the scale at the bottom. The middle panels show gene name, their direction of transcription and corresponding genome position.
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| Title | Year | PMID |
|---|---|---|
| Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. | 2010 | 21102462 |
External
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| Investigation of peripubertal expression of Lin28a and Lin28b in C57BL/6 female mice. | Grieco A et al. | β | 2013 | β |
| Lin28a regulates germ cell pool size and fertility. | Shinoda G et al. | β | 2013 | β |
| LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo. | Lee YT et al. | β | 2013 | β |
| Molecular and gene network analysis of thyroid transcription factor 1 (TTF1) and enhanced at puberty (EAP1) genes in patients with GnRH-dependent pubertal disorders. | Cukier P et al. | β | 2013 | β |
| Replication of genetic loci for ages at menarche and menopause in the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) study. | Carty CL et al. | β | 2013 | β |
| Replication of LIN28B SNP association with age of menarche in young Filipino women. | Croteau-Chonka DC et al. | β | 2013 | β |
| Shared genetic factors for age at natural menopause in Iranian and European women. | Rahmani M et al. | β | 2013 | β |
| The ageing ovary and uterus: new biological insights. | Nelson SM et al. | β | 2013 | β |
| The MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to facilitate homologous recombination. | Park J et al. | β | 2013 | β |
| The role of miRNAs in regulating gene expression networks. | Gurtan AM et al. | β | 2013 | β |
| 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium. | Warren H et al. | β | 2012 | β |
| Absence of functional LIN28B mutations in a large cohort of patients with idiopathic central precocious puberty. | Silveira-Neto AP et al. | β | 2012 | β |
| A LIN28B polymorphism predicts for colon cancer survival. | Ye Y et al. | β | 2012 | β |
| Analysis of LIN28A in early human ovary development and as a candidate gene for primary ovarian insufficiency. | El-Khairi R et al. | β | 2012 | β |
| ApoE genotypes are associated with age at natural menopause in Chinese females. | Meng FT et al. | β | 2012 | β |
| A potential mechanism for the sexual dimorphism in the onset of puberty and incidence of idiopathic central precocious puberty in children: sex-specific kisspeptin as an integrator of puberty signals. | Bianco SD | β | 2012 | β |
| A single-nucleotide polymorphism in the EAP1 gene is associated with amenorrhea/oligomenorrhea in nonhuman primates. | Lomniczi A et al. | β | 2012 | β |
| Association of 8q22.3 locus in Chinese Han with idiopathic premature ovarian failure (POF). | Qin Y et al. | β | 2012 | β |
| Association of LIN28B with adult adiposity-related traits in females. | Leinonen JT et al. | β | 2012 | β |
| Clinical practice. Delayed puberty. | Palmert MR et al. | β | 2012 | β |
| Current understanding of ovarian aging. | Li Q et al. | β | 2012 | β |
| Deciphering puberty: novel partners, novel mechanisms. | Tena-Sempere M | β | 2012 | β |
| Dissection of the maternal effects on puberty onset by embryo transplantation in mouse. | Zhou Y et al. | β | 2012 | β |
| Environmental and genetic factors influence age at menarche in women with polycystic ovary syndrome. | Carroll J et al. | β | 2012 | β |
| Environmental epigenetics: a role in endocrine disease? | Fleisch AF et al. | β | 2012 | β |
| ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure. | Qin Y et al. | β | 2012 | β |
| Functional study of risk loci of stem cell-associated gene lin-28B and associations with disease survival outcomes in epithelial ovarian cancer. | Lu L et al. | β | 2012 | β |
| Genetic markers of ovarian follicle number and menopause in women of multiple ethnicities. | Schuh-Huerta SM et al. | β | 2012 | β |
| Genetics of age at menarche: a systematic review. | Dvornyk V et al. | β | 2012 | β |
| Genome-wide copy number variation association analyses for age at menarche. | Liu YZ et al. | β | 2012 | β |
| How does Lin28 let-7 control development and disease? | Thornton JE et al. | β | 2012 | β |
| Investigating the role of X chromosome breakpoints in premature ovarian failure. | Baronchelli S et al. | β | 2012 | β |
| LIN28B polymorphisms are associated with central precocious puberty and early puberty in girls. | Park SW et al. | β | 2012 | β |
| Lin-28 homologue A (LIN28A) promotes cell cycle progression via regulation of cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25 homolog A (CDC25A) expression in cancer. | Li N et al. | β | 2012 | β |
| Low digit ratio predicts early age at menarche in Colombian schoolgirls. | Oberg AS et al. | β | 2012 | β |
| MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination. | Lutzmann M et al. | β | 2012 | β |
| Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks. | Nishimura K et al. | β | 2012 | β |
| Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. | Stolk L et al. | β | 2012 | β |
| Replication of loci influencing ages at menarche and menopause in Hispanic women: the Women's Health Initiative SHARe Study. | Chen CT et al. | β | 2012 | β |
| Reproductive aging-associated common genetic variants and the risk of breast cancer. | He C et al. | β | 2012 | β |
| The search for longevity and healthy aging genes: insights from epidemiological studies and samples of long-lived individuals. | Murabito JM et al. | β | 2012 | β |
| Associations between the pubertal timing-related variant in LIN28B and BMI vary across the life course. | Ong KK et al. | β | 2011 | β |
| Association study in Taiwanese girls with precocious puberty. | Chou IC et al. | β | 2011 | β |
| BR-squared: a practical solution to the winner's curse in genome-wide scans. | Sun L et al. | β | 2011 | β |
| Caenorhabditis elegans reproductive aging: Regulation and underlying mechanisms. | Luo S et al. | β | 2011 | β |
| Cellular and molecular mechanisms of various types of oocyte aging. | Takahashi T et al. | β | 2011 | β |
| Child health, developmental plasticity, and epigenetic programming. | Hochberg Z et al. | β | 2011 | β |
| Common genetic variants are significant risk factors for early menopause: results from the Breakthrough Generations Study. | Murray A et al. | β | 2011 | β |
| Estimation of odds ratios of genetic variants for the secondary phenotypes associated with primary diseases. | Wang J et al. | β | 2011 | β |
| Familial concordance for age at menarche: analyses from the Breakthrough Generations Study. | Morris DH et al. | β | 2011 | β |
| Genetic defects of ovarian TGF-Ξ²-like factors and premature ovarian failure. | Persani L et al. | β | 2011 | β |
| Is low digit ratio linked with late menarche? Evidence from the BBC internet study. | Manning JT et al. | β | 2011 | β |
| LIN28B, LIN28A, KISS1, and KISS1R in idiopathic central precocious puberty. | Tommiska J et al. | β | 2011 | β |
| LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer. | Permuth-Wey J et al. | β | 2011 | β |
| New genetic factors implicated in human GnRH-dependent precocious puberty: the role of kisspeptin system. | Teles MG et al. | β | 2011 | β |
| Novel breast cancer susceptibility locus at 9q31.2: results of a genome-wide association study. | Fletcher O et al. | β | 2011 | β |
| Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. | Pierce BL et al. | β | 2011 | β |
| Second to fourth digit ratio: a predictor of adult penile length. | Choi IH et al. | β | 2011 | β |
| The genetics of bone loss: challenges and prospects. | Mitchell BD et al. | β | 2011 | β |
| The timing of the age at which natural menopause occurs. | Gold EB | β | 2011 | β |
| Whole genome associated studies for age at menarche. | Elks CE et al. | β | 2011 | β |
| A large-scale candidate gene association study of age at menarche and age at natural menopause. | He C et al. | β | 2010 | β |
| Association weight matrix for the genetic dissection of puberty in beef cattle. | Fortes MR et al. | β | 2010 | β |
| A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure. | Medland SE et al. | β | 2010 | β |
| Distinct variants at LIN28B influence growth in height from birth to adulthood. | WidΓ©n E et al. | β | 2010 | β |
| Do grandmothers who play favorites sow seeds of genomic conflict? | Wilder JA | β | 2010 | β |
| Genetic determinants of pubertal timing in the general population. | Gajdos ZK et al. | β | 2010 | β |
| Genetics basis for GnRH-dependent pubertal disorders in humans. | Silveira LF et al. | β | 2010 | β |
| Genetic variation in CYP11A1 and StAR in relation to endometrial cancer risk. | Terry K et al. | β | 2010 | β |
| Identification of microRNAs regulating reprogramming factor LIN28 in embryonic stem cells and cancer cells. | Zhong X et al. | β | 2010 | β |
| miRNAs give worms the time of their lives: small RNAs and temporal control in Caenorhabditis elegans. | Resnick TD et al. | β | 2010 | β |
| Premature ovarian failure. | Shelling AN | β | 2010 | β |
| The pursuit of genome-wide association studies: where are we now? | Ku CS et al. | β | 2010 | β |
| The transcriptional control of female puberty. | Ojeda SR et al. | β | 2010 | β |
| Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. | Elks CE et al. | β | 2010 | β |
| Genetic and genomic insights into age at natural menopause. | Moron FJ et al. | β | 2009 | β |
| Genetics of reproductive lifespan. | Hartge P | β | 2009 | β |
| Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. | Hagan JP et al. | β | 2009 | β |
| Menopause, evolution and changing cultures. | Shaw LM et al. | β | 2009 | β |
| Multigenic combination of estrogen-related genes is associated with age at natural menopause in a Spanish population. | Mendoza N et al. | β | 2009 | β |
| Ovarian aging: mechanisms and clinical consequences. | Broekmans FJ et al. | β | 2009 | β |