Identifying therapeutic targets for primary ovarian insufficiency through integrated genomic analyses.

Humans Female Primary Ovarian Insufficiency / genetics Genome-Wide Association Study Quantitative Trait Loci Genomics / methods Genetic Predisposition to Disease Polymorphism, Single Nucleotide
Genome-wide Mendelian randomization Primary ovarian insufficiency Therapeutic target

Journal

Journal of ovarian research
ISSN: 1757-2215
Titre abrégé: J Ovarian Res
Pays: England
ID NLM: 101474849

Informations de publication

Date de publication:
02 Oct 2024
Historique:
received: 07 08 2024
accepted: 25 09 2024
medline: 3 10 2024
pubmed: 3 10 2024
entrez: 2 10 2024
Statut: epublish

Résumé

Primary ovarian insufficiency (POI) is a disorder characterized by the premature decline in ovarian function, leading to significant fertility and health impacts on women under 40. The unclear etiology of POI hinders the development of effective treatments, highlighting the need for novel therapeutic targets. This study employed genome-wide association analysis (GWAS) integrated with expression quantitative trait loci (eQTL) data from the GTEx and eQTLGen databases. Mendelian randomization (MR) and colocalization analyses were conducted to investigate causal relationships between genetic variants and POI and to identify potential therapeutic targets. We identified 431 genes with available index cis-eQTL signals, of which four (HM13, FANCE, RAB2A, and MLLT10) were significantly associated with POI. Colocalization analysis revealed strong evidence for FANCE and RAB2A, indicating their potential as therapeutic targets. Subsequent druggability assessments identified FANCE and RAB2A as promising candidates for POI treatment, supported by their involvement in DNA repair and autophagy regulation, respectively. Our study establishes a causal link between specific genes and POI, highlighting FANCE and RAB2A as potential drug targets. These findings provide a foundation for future research and therapeutic development, aiming to improve outcomes for women with POI. Validation in further trials is necessary to confirm these potential targets.

Sections du résumé

BACKGROUND BACKGROUND
Primary ovarian insufficiency (POI) is a disorder characterized by the premature decline in ovarian function, leading to significant fertility and health impacts on women under 40. The unclear etiology of POI hinders the development of effective treatments, highlighting the need for novel therapeutic targets.
METHODS METHODS
This study employed genome-wide association analysis (GWAS) integrated with expression quantitative trait loci (eQTL) data from the GTEx and eQTLGen databases. Mendelian randomization (MR) and colocalization analyses were conducted to investigate causal relationships between genetic variants and POI and to identify potential therapeutic targets.
RESULTS RESULTS
We identified 431 genes with available index cis-eQTL signals, of which four (HM13, FANCE, RAB2A, and MLLT10) were significantly associated with POI. Colocalization analysis revealed strong evidence for FANCE and RAB2A, indicating their potential as therapeutic targets. Subsequent druggability assessments identified FANCE and RAB2A as promising candidates for POI treatment, supported by their involvement in DNA repair and autophagy regulation, respectively.
CONCLUSIONS CONCLUSIONS
Our study establishes a causal link between specific genes and POI, highlighting FANCE and RAB2A as potential drug targets. These findings provide a foundation for future research and therapeutic development, aiming to improve outcomes for women with POI. Validation in further trials is necessary to confirm these potential targets.

Identifiants

DOI: 10.1186/s13048-024-01524-y PMID: 39358799
pubmed: 39358799
doi: 10.1186/s13048-024-01524-y
pii: 10.1186/s13048-024-01524-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

193

Subventions

Organisme : the Scientific Research Project of the Sichuan Maternal and Child Health Association
ID : 22FXYB02
Organisme : the Scientific Research Project of the Sichuan Maternal and Child Health Association
ID : 22FXYB12

Informations de copyright

© 2024. The Author(s).

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Auteurs

Haihong Du (H)

Department of Gynecology, Meishan Women and Children's Hospital, Meishan, Sichuan, China.

Pengfei Zeng (P)

School of Acu-Mox and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

Xuyi Liu (X)

Department of Gynecology, Meishan Women and Children's Hospital, Meishan, Sichuan, China.

Jun Zhang (J)

Department of Traditional Chinese Medicine, Meishan Women and Children's Hospital, Meishan, Sichuan, China.

Zhonglu Huang (Z)

Department of Gynecology, Meishan Women and Children's Hospital, Meishan, Sichuan, China. 13980360220@163.com.

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questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identifying therapeutic targets for primary...
questionsmedicales.fr › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Insuffisance ovarienne primitive › Identifying therapeutic targets for primary...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Identifying therapeutic targets for primary...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Locus de caractère quantitatif › Identifying therapeutic targets for primary...
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questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Identifying therapeutic targets for primary...