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Evidence From Men for Ovary-independent Effects of Genetic Risk Factors for Polycystic Ovary Syndrome.
Zhu, Jia; Pujol-Gualdo, Natàlia; Wittemans, Laura B L; Lindgren, Cecilia M; Laisk, Triin; Hirschhorn, Joel N; Chan, Yee-Ming.
Afiliação
  • Zhu J; Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Pujol-Gualdo N; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wittemans LBL; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Lindgren CM; Estonian Genome Centre, Institute of Genomics, University of Tartu 51010, Tartu, Estonia.
  • Laisk T; Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Centre, Oulu University Hospital, University of Oulu FI-90014, Oulu, Finland.
  • Hirschhorn JN; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 ZFZ, UK.
  • Chan YM; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK.
J Clin Endocrinol Metab ; 107(4): e1577-e1587, 2022 03 24.
Article em En | MEDLINE | ID: mdl-34969092
ABSTRACT
CONTEXT Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction and hyperandrogenism and can be associated with cardiometabolic dysfunction, but it remains unclear which of these features are inciting causes and which are secondary consequences.

OBJECTIVE:

To determine whether ovarian function is necessary for genetic risk factors for PCOS to produce nonreproductive phenotypes. DESIGN, SETTING, AND

PARTICIPANTS:

Cohort of 176 360 men in the UK Biobank and replication cohort of 37 348 men in the Estonian Biobank. MAIN OUTCOME

MEASURES:

We calculated individual PCOS polygenic risk scores (PRS), tested for association of these PRS with PCOS-related phenotypes using linear and logistic regression and performed mediation analysis.

RESULTS:

For every 1 SD increase in the PCOS PRS, men had increased odds of obesity (odds ratio [OR] 1.09; 95% CI, 1.08-1.10; P = 1 × 10-49), type 2 diabetes mellitus (T2DM) (OR 1.08; 95% CI, 1.05-1.10; P = 3 × 10-12), coronary artery disease (CAD) (OR 1.03; 95% CI, 1.01-1.04; P = 0.0029), and marked androgenic alopecia (OR 1.03; 95% CI, 1.02-1.05; P = 3 × 10-5). Body mass index (BMI), hemoglobin A1c, triglycerides, and free androgen index increased as the PRS increased, whereas high-density lipoprotein cholesterol and SHBG decreased (all P < .0001). The association between the PRS and CAD appeared to be completely mediated by BMI, whereas the associations with T2DM and marked androgenic alopecia appeared to be partially mediated by BMI.

CONCLUSIONS:

Genetic risk factors for PCOS have phenotypic consequences in men, indicating that they can act independently of ovarian function. Thus, PCOS in women may not always be a primary disorder of the ovaries.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome do Ovário Policístico / Diabetes Mellitus Tipo 2 Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome do Ovário Policístico / Diabetes Mellitus Tipo 2 Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article