Article Text

Download PDFPDF
Associations between age of menarche and genetic variation in women of African descent: genome-wide association study and polygenic score analysis
  1. Molly Scannell Bryan1,
  2. Temidayo Ogundiran2,
  3. Oladosu Ojengbede3,
  4. Wei Zheng4,
  5. William Blot4,
  6. Susan Domcheck5,
  7. Anselm Hennis6,
  8. Barbara Nemesure7,
  9. Stefan Ambs8,
  10. Olufunmilayo I Olopade9,
  11. Dezheng Huo10
  1. 1Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois, USA
  2. 2Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria, Ibadan, Nigeria
  3. 3Center for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria
  4. 4Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  5. 5Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  6. 6Chronic Disease Research Centre, Tropical Medicine Research Institute, The University of the West Indies, Bridgetown, Barbados
  7. 7Department of Preventative Medicine, State University of New York at Stony Brook, Stony Brook, New York, USA
  8. 8Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland, USA
  9. 9Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois, USA
  10. 10Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA
  1. Correspondence to Dr Dezheng Huo, Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA; dhuo{at}


Introduction Many diseases of adulthood are associated with a woman’s age at menarche. Genetic variation affects age at menarche, but it remains unclear whether in women of African ancestry the timing of menarche is regulated by genetic variants that were identified in predominantly European and East Asian populations.

Methods We explored the genetic architecture of age at menarche in 3145 women of African ancestry who live in the USA, Barbados and Nigeria. We undertook a genome-wide association study, and evaluated the performance of previously identified variants.

Results One variant was associated with age at menarche, a deletion at chromosome 2 (chr2:207216165) (p=1.14×10−8). 349 genotyped variants overlapped with these identified in populations of non-African ancestry; these replicated weakly, with 51.9% having concordant directions of effect. However, collectively, a polygenic score constructed of those previous variants was suggestively associated with age at menarche (beta=0.288 years; p=0.041). Further, this association was strong in women enrolled in the USA and Barbados (beta=0.445 years, p=0.008), but not in Nigerian women (beta=0.052 years; p=0.83).

Discussion This study suggests that in women of African ancestry the genetic drivers of age at menarche may differ from those identified in populations of non-African ancestry, and that these differences are more pronounced in women living in Nigeria, although some associated trait loci may be shared across populations. This highlights the need for well-powered ancestry-specific genetic studies to fully characterise the genetic influences of age at menarche.

  • epidemiology
  • reproductive health
  • genetic epidem

Data availability statement

Data are available in a public, open access repository. The genotype data of the Root genome-wide association study are posted in dbGaP (

Statistics from

Data availability statement

Data are available in a public, open access repository. The genotype data of the Root genome-wide association study are posted in dbGaP (

View Full Text


  • Contributors All authors contributed substantially to the, conception, design, acquisition, analysis or interpretation of the data, and contributed to drafting and revising the work and giving final approval, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.Conception and design: MSB and DH; acquisition of data: TO, OO, WZ, WB, SD, AH, BN, SA, OIO and DH; Data analysis: MSB, DH; Writing of the initial manuscript: MSB, DH; Review of the manuscript: MSB, TO, OO, WZ, WB, SD, AH, BN, SA, OIO and DH. DH is responsible for the overall content as the guarantor.

  • Funding This study was funded by the by the National Institute of Health (grant numbers T32CA057699, 5R25-CA057699, R01CA142996 and R01CA228198) and Breast Cancer Research Foundation (BCRF-21-071).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.