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Whole Exome Sequencing of PCOS

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of reproductive age and is characterized by hyperandrogenism, oligomenorrhea/amenorrhea, and polycystic ovaries.

The goals of this project were to 1) generate a comprehensive catalog of likely causal PCOS associated variants, 2) establish the functional consequences of the genetic variants identified by whole exome sequencing (WES) using bioinformatic and molecular strategy, and 3) identify genes and molecular pathways that are genetically impaired in PCOS with the goal of providing more targeted treatment for PCOS.

To achieve these goals, we carried out WES on a total of 1064 samples corresponding to 1049 unique subjects (15 subjects had duplicate sequencing samples). The samples include 731 PCOS cases (731 unique), 318 controls (309 controls), and 15 samples of unknown phenotype (6 PPCOSII, 9 HapMap controls). Controls are reproductive age women with normal androgens and regular menses as phenotype control. We designed a Custom WES array which includes the standard CIDR WES array plus 9.8 Mb of Twist Custom Design added content encoding genomic regions in linkage disequilibrium with PCOS associated GWAS regions. Sequencing was performed at the Center for Inherited Disease Research (CIDR), Johns Hopkins University School of Medicine. Target templates are sequenced to >100x coverage using paired-end reads on the Illumina NovaSeq6000 platform.