News & Events

“Paternal age, de novo mutation, and age at onset among co-affected schizophrenia sib-pairs” published in Molecular Psychiatry

Delayed fatherhood has long been linked to an increased risk of schizophrenia in offspring, but the underlying mechanism remains unclear. In collaboration with Dr. Shi-Heng Wang from the NHRI, we performed trio analysis on schizophrenia sib-pairs to identify de novo mutations (DNMs) using whole-genome sequencing. We discovered that DNMs were associated with both advanced paternal age and an earlier schizophrenia onset in probands. Further, causal mediation analysis showed that DNMs significantly mediated the effect of paternal age on the age of schizophrenia onset. Our study offers a potential causal explanation linking paternal age-related mutations to increased psychiatric risk in offspring.

Reference:
Feng, Y.-C. A., Chen, W. J., Lin, M. C., Hsu, J. S., Cheng, C. F., Liu, C. H., Hwu, H. G., Huang, Y. T., Lu, T. P., & Wang, S. H. (2025) Paternal age, de novo mutation, and age at onset among co-affected schizophrenia sib-pairs: whole-genome sequencing in multiplex families. Molecular Psychiatry, 30(8), 3560–3567.

Our first lab hike takes us up Jinmian Mountain (金面山) on a beautiful afternoon—and hopefully, not our last!

ASHG, WCPG, and IASC-ARS

Kudos to all the first-time attendees from the lab for presenting their work at the World Congress of Psychiatric Genetics (WCPG), American Society of Human Genetics (ASHG), and the Asian Regional Section of the International Association for Statistical Computing (IASC-ARS) conference.

Yi-Ru Lin received the institutional Oral Presentation award for her research on deciphering the genetics of epilepsy in East and Southeast Asian populations.

Welcome Dr. Yun-Han Wang joining our lab as a postdoc. Dr. Wang earned her PhD in pharmacoepidemiology from Karolinska Institutet, and she is excited to explore new avenues in genetics!

“Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes” from the Epi25 Collaborative now published in Nature Neuroscience

Back in 2019, we published a whole-exome sequencing (WES) study of epilepsy as part of the Epi25 Collaborative that revealed shared and distinct burden of ultra-rare deleterious variants (URVs) across severe and less severe epilepsy subtypes and highlighted a ubiquitous role for defects in GABAergic inhibition. Built upon the previous work, a larger WES from Epi25 published this year further nominated potential novel risk genes, with an enriched role in synaptic transmission and neuronal excitability. Along with URV burden observed in gene sets and copy number variations, these findings map out an expanded genetic architecture of epilepsy, highlighting a convergence of different genetic risk factors within the same genes.

Reference:
Epi25 Collaborative. (Feng et al. 2019) Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals. American Journal of Human Genetics, 105(2), 267-282.
Epi25 Collaborative. (Chen et al. 2024) Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes. Nature Neuroscience, 27(10), 1864-1879.

Aaron Chang and Wen-Lan Chen have joined the lab as research assistants. Welcome aboard!

Farewell dinner for lab members… “Who and where do you see yourself in ten years?”

Congratulations to Shaun Luo on receiving the College Student Research Scholarship by the National Science and Technology Council!

恭喜士翔獲得國科會大專生專題計畫補助！