Genetic variants and environmental factors associated with hormonal markers of ovarian reserve in Caucasian and African American women

Hum Reprod. 2012 Feb;27(2):594-608. doi: 10.1093/humrep/der391. Epub 2011 Nov 24.


Background: The ovarian reserve (number and quality of oocytes) is correlated with reproductive potential as well as somatic health, and is likely to have multiple genetic and environmental determinants. Several reproductive hormones are closely linked with the oocyte pool and thus can serve as surrogate markers of ovarian reserve. However, we know little about the underlying genes or genetic variants.

Methods: We analyzed genetic variants across the genome associated with two hormonal markers of ovarian reserve, FSH and anti-Mullerian hormone, in a reproductively normal population of Caucasian (n = 232) and African American (n = 200) women, aged 25-45 years. We also examined the effects of environmental or lifestyle factors on ovarian reserve phenotypes.

Results: We identified one variant approaching genome-wide significance (rs6543833; P= 8.07 × 10⁻⁸) and several nominal variants nearby and within the myeloid-associated differentiation marker-like (MYADML) gene, that were associated with FSH levels in African American women; these were validated in Caucasian women. We also discovered effects of smoking and oral contraceptive use on ovarian reserve phenotypes, with alterations in several reproductive hormones.

Conclusions: This work is the largest study on ovarian reserve in women of reproductive age and is the only genome-wide study on ovarian reserve markers. The genes containing or near the identified variants have no known roles in ovarian biology and represent interesting candidate genes for future investigations. The discovery of genetic markers may lead to better long-range predictions of declining ovarian function, with implications for reproductive and somatic health.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Black or African American
  • California
  • Cohort Studies
  • Contraceptives, Oral / adverse effects
  • Female
  • Gene-Environment Interaction*
  • Genetic Markers
  • Genome-Wide Association Study
  • Gonadotropins / blood
  • Health Promotion*
  • Humans
  • Life Style
  • Oogenesis*
  • Ovary / cytology
  • Ovary / physiology*
  • Ovary / physiopathology
  • Primary Ovarian Insufficiency / ethnology
  • Primary Ovarian Insufficiency / etiology*
  • Primary Ovarian Insufficiency / genetics*
  • Primary Ovarian Insufficiency / prevention & control
  • Prospective Studies
  • Reproductive Health* / ethnology
  • Smoking / adverse effects
  • Smoking / blood
  • White People


  • Contraceptives, Oral
  • Genetic Markers
  • Gonadotropins