Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2

Context: Polycystic ovary syndrome ( PCOS) is a common endocrine disorder that is believed to have a genetic basis. However, no specific susceptibility gene or region has been conclusively identified. Objective: The objective of this study was to duplicate a previous study that localized a PCOS susceptibility region to chromosome 19p13.2 and to narrow the susceptibility region. Design: This study was designed to test for genetic linkage and association between PCOS and short tandem repeat polymorphisms in 367 families, by analysis of linkage and family-based association. Setting: The study was conducted at academic medical centers. Patients or Other Participants: We studied 367 families of predominantly European origin with at least one PCOS patient. Families included 107 affected sibling ( sister) pairs ( ASPs) in 83 families, and 390 trios with both parents and an affected daughter. The data set comprises two independent groups. Set 1 consists of 44 ASPs and 163 trios. Set 2 consists of 63 ASPs and 227 trios. Intervention(s): The intervention was the drawing of blood for DNA extraction. Main Outcome Measure: We employed measures of evidence for linkage and association between PCOS and 19 STRs. Results: Linkage with PCOS was observed over a broad region of chromosome 19p13.2. The strongest evidence for association was observed with D19S884 ( chi(2) = 11.85; nominal P < 0.0006; permutation P = 0.034) and duplicated our earlier findings. Conclusions: The present analysis suggests that a PCOS susceptibility locus maps very close to D19S884. Additional studies that systematically characterize DNA sequence variation in the immediate area of D19S884 are required to identify the PCOS susceptibility variant.