How to Map the Genetic Basis for Conditions that are Comorbid with Male Infertility

Studying conditions that are comorbid with infertility can provide a picture of the overall health of a patient population that is younger than the typical cases of age-related diseases that preoccupy our health care system. If strong predictive relationships could be established between infertility and life-threatening disease, interventions can be established early in life for at-risk individuals. Here, we discuss how genomic tools can be used to identify diseases and traits that are likely to be comorbid with male infertility. We divide these approaches broadly into two categories: direct and indirect. Direct approaches require knowledge of the specific genetic variants associated with male infertility, while indirect approaches can work with only gene lists, or even no a priori knowledge of disease-gene architecture. Using existing data from human and mouse studies, we demonstrate that one indirect approach based on gene networks provides support for the recent epidemiological findings that infertility is a risk factor for cancer and cardiovascular disease. Finding comorbidities of male infertility is an important goal for the reproductive medicine community. We outline existing resources that will play a valuable role in this quest, and describe new resources that must be developed for maximum progress.