Genome-wide linkage and association study identifies novel genes and pathways implicated in polycystic ovarian syndrome

M. Amin, C. Gragnoli

INSERM, US14-Orphanet, Paris, France. claudia.gragnoli@gmail.com

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• Genomics
• Gynecology

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a complex heterogeneous condition that affects women of reproductive age, conferring increased cardiovascular morbidity and mortality. The syndrome is characterized by oligomenorrhea, hyperandrogenism, and/or polycystic ovaries and is often associated with obesity and type 2 diabetes. Individuals are predisposed to PCOS by environmental factors and risk variants in genes mostly involved in ovarian steroidogenesis and/or insulin resistance. Genetic risk factors have been identified by both familial and genome-wide (GW) association studies. However, most genetic components are still unknown and missing heritability needs to be elucidated. To learn more about the genetic determinants of PCOS, we performed a GW study in genetically highly homogeneous peninsular families.

PATIENTS AND METHODS: We conducted the first GW-linkage and linkage disequilibrium (i.e., linkage + association) study in Italian families with PCOS.

RESULTS: We identified several novel risk variants, genes, and pathways potentially implicated in the pathogenesis of PCOS. Specifically, we detected 79 novel variants with significant GW-linkage and/or -association with PCOS across 4 inheritance models (p < 0.00005), of which 50 variants were within 45 novel PCOS-risk genes.

CONCLUSIONS: This is the first GW-linkage and linkage disequilibrium study performed in peninsular Italian families and reporting novel genes in PCOS.

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