Inherited genetic variants influence age-associated mosaic chromosomal errors in human blood
A large genomic analysis reveals over 800 inherited variants and structural features that alter how frequently chromosomes missegregate in aging individuals.
medRxiv : the preprint server for health sciences · Si Y et al. · Paper published 9 Sep 2026
In a preprint analyzing blood whole-genome sequencing from 840,853 humans, researchers investigated how inherited genetics shapes susceptibility to mosaic chromosomal aneuploidies. They identified autosomal gains in approximately 70,000 individuals, as well as ubiquitous loss of the X chromosome in females and the Y chromosome in males, with each sex chromosome loss showing over 50 percent heritability. Genome-wide association analyses of 12 mosaic aneuploidies revealed more than 800 common inherited variants that influence the generation and proliferation of aneuploid cells. Variants in mitotic spindle assembly checkpoint genes consistently influenced aneuploidy across most chromosomes. Conversely, a missense variant in the kinetochore gene PMF1 improved segregation fidelity for some chromosomes at the cost of others. Inherited structural features also exerted large effects, including a hybrid centromere that raised chromosome 22 gain risk four-fold and repeat array variations that drove a four-fold range in X chromosome loss.
Why it matters
Mosaic chromosomal aneuploidies in blood commonly emerge as people age. Identifying the genetic factors behind mitotic errors provides tools to assess how clonal somatic mutations influence health and aging biology.
Caveats
This study is an observational analysis released as a preprint and has not yet completed peer review. The findings are based on leukocyte genomes and may not reflect mosaic aneuploidy dynamics in other tissues.
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
Genetic mechanisms of mitotic error in 840,853 blood genomes
Si Y, Kamitaki N, Tang D et al.
medRxiv : the preprint server for health sciences · 9 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Relevant
- News value
- Important
- 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.