Genetic Risk for Polycystic Ovary Syndrome

Fifteen gene regions that significantly increase risk for polycystic ovary syndrome (PCOS) are shown by red dots that lie above the green line, indicating high statistical significance.
Fifteen gene regions that significantly increase risk for polycystic ovary syndrome (PCOS) are shown by red dots that lie above the green line, indicating high statistical significance.

Polycystic ovary syndrome (PCOS) is characterized by excessive androgen hormone, irregular menstrual cycles, and polycystic ovaries on ultrasound. Affected women also frequently experience metabolic disturbances, including obesity, and face increased risk for type 2 diabetes. University of Utah Health investigator Corrine Welt, MD, and collaborators performed an international meta-analysis of whole genome association studies combining over 10 million genetic markers in more than 10,000 European women with PCOS and 100,000 controls. 

They found three new risk variants associated with PCOS. The data demonstrate that the genetic architecture does not differ based on the diagnostic criteria used for PCOS. They also demonstrate a genetic pathway in PCOS that is shared with male pattern baldness, representing the first evidence for shared disease biology for PCOS in men. The data also demonstrate a novel genetic pathway associated with depression, demonstrating linked genetic risk for PCOS and depression. It also demonstrated that the genetic architecture underlying PCOS remains the same regardless of which criteria are used for diagnosis. 

These discoveries provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential, and mental health. The data will help physicians better target underlying risk factors and comorbid disease in women with PCOS.

References:

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Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Hayes MG, Urbanek M, Ehrmann DA, Armstrong LL, Lee JY, Sisk R, Karaderi T, Barber TM, McCarthy MI, Franks S, Lindgren CM, Welt CK, Diamanti-Kandarakis E, Panidis D, Goodarzi MO, Azziz R, Zhang Y, James RG, Olivier M, Kissebah AH; Reproductive Medicine Network, Stener-Victorin E, Legro RS, Dunaif A. Nat Commun. 2015 Aug 18;6:7502.

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Gene variants associated with age at menopause are also associated with polycystic ovary syndrome, gonadotrophins and ovarian volume. Saxena R, Bjonnes AC, Georgopoulos NA, Koika V, Panidis D, Welt CK. Hum Reprod. 2015 Jul;30(7):1697-1703.

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Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Day FR, Hinds DA, Tung JY, Stolk L, Styrkarsdottir U, Saxena R, Bjonnes A, Broer L, Dunger DB, Halldorsson BV, Lawlor DA, Laval G, Mathieson I, McCardle WL, Louwers Y, Meun C, Ring S, Scott RA, Sulem P, Uitterlinden AG, Wareham NJ, Thorsteinsdottir U, Welt C, Stefansson K, Laven JSE, Ong KK, Perry JRB. Nat Commun. 2015 Sep 29;6:8464.

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