The quest for genetic sequence variants conferring risk of endometriosis

Abstract

In the last two decades, numerous genetic association studies, including genome-wide genetic association studies, aimed at identifying DNA variants conferring risk of endometriosis have been published, and many polymorphisms have been identified. However, each and every one of the identified polymorphisms invariably has a small, even minute, effect, explaining merely a minuscule percentage of the heritability. More disconcertingly, these publications have so far contributed little to our understanding of the pathogenesis or pathophysiology of endometriosis. As with many other complex diseases or traits, there has been a glaring gap between the estimated heritability of the disease and the disease risk variability that can be explained by the identified DNA variants, a phenomenon called “the missing heritability.” This chapter provides a primer on genetic studies of complex diseases such as endometriosis, explaining the methods for demonstration of genetic components for a disease, and methods to identify the genes or genetic variants. It also provides some explanations as to why a “missing heritability” problem also exists in endometriosis.