Evidence map›Paper›PMID 40832409›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Pathogenic variation in insulin resistance genes is common in polycystic ovary syndrome (PCOS): a strategy for causal gene discovery using whole-exome sequencing (WES) in complex traits.

Rosemary Bauer, Chloe Parker, Zulma Cardona Matos, M Geoffrey Hayes, Allen R Kunselman, Richard S Legro, Corrine K Welt, Margrit Urbanek

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Rosemary BauerDivision of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.ORCID 0000-0002-0350-1666
Chloe ParkerDivision of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.ORCID 0000-0001-6257-2272
Zulma Cardona MatosDivision of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
M Geoffrey HayesDivision of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.ORCID 0000-0002-4617-3981
Allen R KunselmanDepartment of Public Health Sciences, Penn State College of Medicine, Hershey, PA, 17033, USA.ORCID 0000-0001-8485-2953
Richard S LegroDepartment of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, PA, 17033, USA.ORCID 0000-0001-9927-7584
Corrine K WeltDivision of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City, Utah, 84132, USA.ORCID 0000-0002-8219-5504
Margrit UrbanekDivision of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.ORCID 0000-0001-6994-7110

Funding

HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
Role of Androgen Excess in Provoking Oxidative Stress in FemalesP50HD044405 · NICHD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DUNAIF, ANDREA E · 2002 to 2017
$17.2M
PROJECT 3 - Steroid-Metabolic Interactions In the Control of GnRH NeuronsU54HD028934 · NICHD · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HAISENLEDER, DANIEL J. · 1998 to 2013
$16.5M
Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1)UL1TR000150 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LLOYD-JONES, DONALD M · 2012 to 2013
$10.1M
PENN STATE CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033184 · NCRR · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI SINOWAY, LAWRENCE I · 2011 to 2011
$4.5M
Treatment of Hyperandrogenism vs. Insulin Resistance in Infertile PCOS WomenR01HD056510 · NICHD · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LEGRO, RICHARD S. · 2008 to 2012
$3.1M
AMH signaling pathway variation in PCOSR01HD100630 · NICHD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI URBANEK, MARGRIT · 2020 to 2024
$3.0M
The Inflammatory Response Pathway in the Etiology of Polycystic Ovary SyndromeR01HD057450 · NICHD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI URBANEK, MARGRIT · 2009 to 2012
$2.1M
The Genetics of Polycystic Ovary SyndromR01HD065029 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI WELT, CORRINE K · 2010 to 2014
$1.7M
Northwestern Center for Reproductive Science Predoctoral Training Program in Reproductive Science, Medicine, and TechnologyT32HD094699 · NICHD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ji-Yong Julie Kim · 2019 to 2026
$1.3M
NCATS NIH HHS UL1 TR000150NCATS NIH HHS UL1 TR000430NCRR NIH HHS UL1 RR025758NCRR NIH HHS UL1 RR033184NICHD NIH HHS P50 HD044405NICHD NIH HHS R01 HD056510NICHD NIH HHS R01 HD057450NICHD NIH HHS R01 HD065029NICHD NIH HHS R01 HD100630NICHD NIH HHS T32 HD094699NICHD NIH HHS U54 HD028934
6 · The paper itself

Abstract

Polycystic ovary syndrome (PCOS) is a complex, multi-system, heritable endocrinopathy that is a common cause of anovulatory infertility in reproductive-aged women. While insulin resistance (IR) is not a diagnostic feature, it is widespread in women with PCOS, and often more severe than in women of similar age and BMI. Conversely, women with rare Mendelian disorders of IR also present with features of PCOS. We hypothesize that PCOS is driven by underlying IR, which can be evaluated through a genetic approach. We curated and stratified 310 genes related to three mechanisms of IR using molecular and clinical criteria. We evaluated protein-altering genetic variation in 102 insulin signaling genes, 29 obesity genes, and 22 dyslipidemia genes from whole-exome sequencing data from 675 PCOS patients. 40 insulin signaling genes, 12 obesity genes, and 10 dyslipidemia genes were significantly enriched for protein-altering variation in PCOS cases compared to healthy population controls. Variants in these 62 significantly enriched genes affected 51% of PCOS cases in our study cohort. The 15 highest ranked genes were selected for follow-up:

Indexed as

complex trait geneticsinsulin resistancemetabolic syndromepolycystic ovary syndrome (PCOS)whole-exome sequencing (WES)

Identifiers

PMID40832409
PMCPMC12363695

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.