Ovarian Morphology Is a Marker of Heritable Biochemical Traits in Sisters With Polycystic Ovaries

Abstract

ABSTRACT Previous studies support the view that a number of genes interacting with environmental factors contribute to the occurrence of the polycystic ovary syndrome (PCOS). There is evidence for heritability of both hyperandrogenism and metabolic abnormalities within families possessing this complex endocrine trait. To determine the mode of inheritance of PCOS and search for candidate genes, affected and unaffected sisters of probands with PCOS have been investigated. This present study tested the hypothesis that ovarian morphology is a marker of inherited biochemical features among sisters of probands with PCOS. The study subjects were 125 probands with PCOS and 214 sisters. Probands were defined as women with polycystic ovaries on ultrasound and symptoms of anovulation or hyperandrogenism or both. Of the 214 sisters, 151 were affected and 63 were unaffected. The control population was 75 women with normal ovaries and regular cycles with no family history suggestive of PCOS. The clinical, endrocrine, and metabolic indices among the probands and their sisters were compared. The quantitative transmission disequilibrium test was used to obtain estimates of broad-sense heritability (the proportional contribution of genetic factors to the total variance of the trait). Compared to probands, affected sisters had fewer symptoms of PCOS; 30% had no symptoms. Serum concentrations of androstenedione, testosterone, LH, and fasting insulin and insulin sensitivity were similar among probands and affected sisters with polycystic ovaries but significantly different from those in unaffected sisters or controls. Moderate to high heritabilities for all traits analyzed were found between probands and affected sisters. In contrast, heritabilities calculated from discordant (affected and unaffected siblings) were substantially lower. The investigators conclude from these findings that although symptoms vary widely between probands with PCOS and affected sisters, polycystic ovarian morphology is a marker of inherited biochemical traits in families of women with PCOS and is central to the etiology of this disorder.