Brain and pituitary gene regulation links to the timing of natural menopause
A large genomic study prioritized hundreds of genetic variants and highlighted candidate cell-type-specific targets associated with female reproductive aging.
Research Square · Farhang-Sardroodi S et al. · Paper published 28 Sep 2026
In a preprint analyzing genomic data from 173,424 women of European ancestry, researchers investigated regulatory mechanisms influencing age at natural menopause. The authors analyzed genome-wide association summary statistics and identified 230 risk loci, of which 108 were novel. Fine-mapping prioritized 216 candidate variants, including 168 novel variants. By integrating transcriptome-wide analyses, Mendelian randomization, and colocalization, the team identified cell-type-specific gene targets in the brain and pituitary. Candidate targets included HSD17B6 in inhibitory neurons, NBR1 and HGS in oligodendrocyte precursor cells, and ERBB4 in pituitary lactotropes. Genetically predicted expression of NBR1 in the ovary and ERBB4 in the pituitary positively associated with age at natural menopause. Additionally, higher genetically predicted expression of HSD17B6 across five brain tissues, as well as NBR1 in the cerebellum, was associated with later menopause.
Why it matters
Understanding the genetic and cell-specific regulators of menopause helps clarify the neuroendocrine pathways controlling female reproductive aging.
Caveats
This work is a preprint that has not yet completed peer review. In addition, the genetic analyses were limited to female participants of European ancestry.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Integrative Functional Genomics Identifies Candidate Brain and Pituitary Regulatory Mechanisms of Reproductive Aging
Farhang-Sardroodi S, Madani A, Rudzicz F
Research Square · 28 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Relevant
- News value
- Notable
- Evidence
- Humans
- Status
- Preprint
Latest stories
Gastrodia elata polysaccharide extends worm lifespan and mitigates age-related deficits in mice
The treatment reduced oxidative stress, suppressed inflammation, and remodeled the gut microbiome in naturally aging mice while prolonging survival in nematodes.
Food science & nutrition · Shi H et al.
Simulated microgravity increases transcriptomic age in human organoids
Culturing human neural, cardiac, and tonsil models in rotating-wall vessels for 24 hours also shifted contraction dynamics and immune gene expression.
bioRxiv · Mu W-C et al.
Rank normalization resolves distinct proteome degradation pathways in cultured cells
A percentile-based normalization method reveals substrate preferences between proteasomal and lysosomal clearance systems in cultured cells.
bioRxiv · Gao Z et al.
Melissic acid reduces senescence in human stem cells via cAMP signaling
A screen of 800 natural compounds identified a phytochemical that activates autophagy and restores cell-cycle activity in models of cellular exhaustion.
Frontiers in pharmacology · Yang K et al.