Nature Medicine：胡志斌/沈洪兵/王铖合作揭示父亲孕前因素影响孩子新生突变及早期发育

TL;DR - A Nature Medicine study (Nanjing Medical University, published 2026-08-07) used ~30× whole-genome sequencing of 7,851 parent-offspring trios (24,030 individuals) from the China National Birth Cohort to build the largest population-scale de novo mutation (DNM) map, showing paternal preconception factors shape offspring DNMs and, through them, early developmental health.

• Parental age effects differ by origin: paternal germline DNMs accumulate linearly with age, while maternal gDNMs accelerate after ~29–32 years with an altered mutational spectrum.
• Advanced paternal age did not directly cause adverse outcomes; its gDNM burden acted indirectly via early developmental phenotypes such as gestational age and birth weight.
• Decomposing ART steps: ICSI was associated with increased paternal gDNMs (mediating preterm birth and low birth weight risk), while GnRH-antagonist ovarian stimulation was associated with increased maternal gDNMs.
• Extended detection to early post-zygotic mosaic mutations (EPZMs): embryo culture/transfer procedures correlated with higher EPZM burden, and specific EPZM types with neurodevelopmental delay risk at age 1.
• Scale is ~20× the team's 2021 Cell Research pilot, supporting a shift from mother-focused to joint parental preconception risk management.