Mendelian randomization identifies circulating proteins as biomarkers for age at menarche and age at natural menopause.
Commun Biol
; 7(1): 47, 2024 01 06.
Article
de En
| MEDLINE
| ID: mdl-38184718
ABSTRACT
Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating proteins associated with altered ANM and AAM using an unbiased two-sample Mendelian randomization (MR) and colocalization approach. By testing causal effects of 1,271 proteins on AAM, we identified 22 proteins causally associated with AAM in MR, among which 13 proteins (GCKR, FOXO3, SEMA3G, PATE4, AZGP1, NEGR1, LHB, DLK1, ANXA2, YWHAB, DNAJB12, RMDN1 and HPGDS) colocalized. Among 1,349 proteins tested for causal association with ANM using MR, we identified 19 causal proteins among which 7 proteins (CPNE1, TYMP, DNER, ADAMTS13, LCT, ARL and PLXNA1) colocalized. Follow-up pathway and gene enrichment analyses demonstrated links between AAM-related proteins and obesity and diabetes, and between AAM and ANM-related proteins and various types of cancer. In conclusion, we identified proteomic signatures of reproductive ageing in women, highlighting biological processes at both ends of the reproductive lifespan.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Ménarche
/
Analyse de randomisation mendélienne
Type d'étude:
Clinical_trials
Limites:
Female
/
Humans
Langue:
En
Journal:
Commun Biol
Année:
2024
Type de document:
Article
Pays d'affiliation:
Canada
Pays de publication:
Royaume-Uni