NEWRESEARCH HORIZON Review The future for genetic studies in reproduction

abstract: Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wideassociation studies (GWAS)haverevolutionized genediscovery forcommon traits anddiseases.ResultsofGWASaredocumented in the Catalog of Published Genome-Wide Association Studies at the National Human Genome Research Institute and report over 70 publica-tions for 32 traits and diseases associated with reproduction. These include endometriosis, uterine fibroids, age at menarche and age at meno-pause. Results that pass appropriate stringent levels of significance are generally well replicated in independent studies. Examples of genetic variation affecting twinning rate, infertility, endometriosis and age at menarche demonstrate that the spectrum of disease-related variants for reproductive traits is similar to most other common diseases. GWAS ‘hits ’ provide novel insights into biological pathways and the translational valueof these studies lies in discoveryof novel gene targets for biomarkers, drug development and greater understanding of environmental factors contributing to disease risk. Results also show that genetic data can help define sub-types of disease and co-morbidity with other traits and diseases. To date, many studies on reproductive traits have used relatively small samples. Future genetic marker studies in large samples with detailed phenotypic and clinical information will yield new insights into disease risk, disease classification and co-morbidity for many diseases associated with reproduction and infertility.