News & Events | Feng Lab

Fathers on Valproate Linked to Offspring Risk?

Wed, 19 Aug 2026 00:00:00 +0000

“Paternal Valproate Exposure and Offspring Neurodevelopmental Outcomes” published in Neurology

In collaboration with CGMH and NHRI, this study looks at whether paternal exposure to valproate (a common and effective drug for epilepsy and bipolar disorder etc.) during spermatogenesis would increase the risk of NDD in their children, using the NHIRD database in Taiwan.

This has been a contentious issue since 2023: an initial report by IQVIA using a Nordic registry found significantly elevated risk, prompting a warning in the UK MHRA to advise against valproate use for male patients less than 55 years of age. However, several follow-up studies—now including our non-Nordic data, with several complementary designs to mitigate confounding—reported otherwise (i.e., null association), calling for a reconsideration of valproate regulation in men of reproductive age.

Reference:
Feng, Y.-C. A., Lin, M.-C., Tseng, C.-H., Wu, C.-S., Tsai, M.-H.*, Wang, S.-H.* (2026). Paternal valproate exposure and offspring neurodevelopmental outcomes. Neurology, 107(6), e218375.

Editorial Comment:
Voinescu, P. E. (2026). Paternal valproate and offspring neurodevelopment: A non-Nordic perspective on an unsettled question. Neurology, 107(6), e218516.

Dr. Anne Feng Received the Ta-You Wu Memorial Award

Thu, 06 Aug 2026 00:00:00 +0000

Recognized for sustained excellence and promise in genetics and population health research by Taiwan’s National Science and Technology Council

Polygenic Risk Prediction for Epilepsy

Thu, 25 Jun 2026 00:00:00 +0000

“Variability in epilepsy polygenic risk prediction across Taiwanese population and clinical cohorts” published in Epilepsia

Our study examined whether polygenic risk scores—measures that combine the effects of many genetic variants—can help identify people at higher risk of epilepsy in more than 600,000 Taiwanese individuals. We found that these genetic scores performed best in carefully characterized clinical samples and were generally more informative for people with earlier-onset epilepsy, particularly genetic generalized epilepsy (GGE). However, their predictive power varied substantially depending on the type of epilepsy and how cases were identified, highlighting the need for caution before using them in clinical practice. Our findings also underscore the importance of improving genetic studies in diverse populations and combining genetic information with richer clinical data to make precision medicine for epilepsy more accurate and equitable.

Reference:
Ke, Y.-S., Tsai, M.-H., Ho, C.-R., Chou, C.-Y., Chen, H.-H., Stevelink, R., …, Sung, S.-F., Lee, M.-C., Chen, J.-T., & Feng, Y.-C. A.* (2026). Variability in epilepsy polygenic risk prediction across Taiwanese population and clinical cohorts. Epilepsia, epi.70353.

Great Science at ESHG 2026

Sat, 13 Jun 2026 00:00:00 +0000

Proud of Yi-Syuan Ke for delivering a talk on our work dissecting depression heterogeneity with Transformer architecture

Mapping the Genetic Architecture of Methylation

Wed, 11 Feb 2026 00:00:00 +0000

“Genetic regulation of methylation across East Asian and European populations” published in Nature Communications

台大公衛學院健統所馮嬿臻老師團隊與國衛院、美國 Broad Institute 合作，發表迄今最大規模的東亞族群 DNA 甲基化遺傳調控研究，刻畫其與複雜疾病風險的關聯。

DNA 甲基化是基因體上重要的化學修飾，可調節基因表現並影響疾病風險，其本身亦受遺傳因素所調控；然而，目前相關研究以歐洲人群為主，東亞族群資料相對匱乏。本研究整合共 7,619 人的漢人族群樣本，鑑定出數十萬個受基因調控的甲基化位點，其中 28,978 個為新興發現。東亞與歐洲族群的甲基化調控機制大多共享，而東亞特有訊號則多來自在歐洲族群中較為少見的變異。此外，本研究利用孟德爾隨機化之因果分析，將遺傳變異、甲基化、基因表現與疾病風險串連，為心血管疾病、糖尿病等複雜疾病的潛在分子機轉提供新線索。研究團隊並公開釋出此東亞 mQTL 資源，為後續族群遺傳研究奠定重要基礎。

Reference:
Liu, R., Chen, T.-T., Xia, Y., Lin, S.-C., Ge, T., Chen, C.-Y.*, Feng, Y.-C. A.*, Huang, H.*, & Lin, Y.-F.* (2026). Genetic regulation of methylation across East Asian and European populations. Nature Communications, 17(1), 2616.

ASHG 2025, Lab Edition

Wed, 15 Oct 2025 00:00:00 +0000

“You’re not just part of the sequence; You complete it.”

Genetic Clues to Treatment-Resistant Depression

Tue, 15 Jul 2025 00:00:00 +0000

“Polygenic dissection of treatment-resistant depression with proxy phenotypes in the UK Biobank” published in Journal of Affective Disorders

For about one in three people with major depressive disorder (MDD), standard antidepressant treatments don’t work. This form, called treatment resistant depression (TRD), leaves patients struggling despite trying at least two different medications.

Our team asked: could genetics help explain who develops TRD—and even guide more personalized treatments?

Using primary-care electronic health records from 230,000 people in the UK Biobank, we identified those likely to have TRD based on their prescription history. Compared to others with depression, these individuals often had an earlier onset of depression, lower employment and education levels, and more frequent hospitalizations.

The genetic findings were clear: TRD showed a much stronger inherited component (20–30% of risk) than depression overall (~8%). People with higher polygenic risk scores (PRS) for MDD, ADHD, and bipolar disorder were more likely to switch medications or use mood stabilizers, while those with a higher genetic risk for schizophrenia specifically predicted the use of antipsychotics. Higher bipolar PRS also increased the likelihood of using electroconvulsive therapy (ECT), lithium, or valproate by 1.27–1.80 fold.

These results support that TRD has a non-trivial genetic basis and highlight the potential of PRS to uncover pharmacogenomic effects that may aid treatment options for managing TRD.

Reference:
Wang, L.-H., Shih, M.-Y., Lin, Y.-F., Kuo, P.-H., & Feng, Y.-C. A.* (2025). Polygenic dissection of treatment-resistant depression with proxy phenotypes in the UK Biobank. Journal of Affective Disorders, 381, 350–359.

College Research Award

Sun, 29 Jun 2025 00:00:00 +0000

Shih-Hsiang (Shaun) Luo received the highest honor at NTU for his bachelor thesis, titled “A multifactorial risk assessment of depression integrating genomic, epigenomic, and psychosocial factors in the Taiwanese population” – Congratulations!

Delayed Fatherhood, DNMs, and Schizophrenia Onset

Wed, 05 Mar 2025 00:00:00 +0000

New paper published in Molecular Psychiatry: Whole-genome sequencing in multiplex families of schizophrenia revealed a mediating role of de novo mutations between paternal age and disease risk

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). 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.

Conference Highlights

Tue, 31 Dec 2024 00:00:00 +0000

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.

Oral Presentation Award

Fri, 29 Nov 2024 00:00:00 +0000

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

New Member Alert

Thu, 21 Nov 2024 00:00:00 +0000

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

Genetic Landscape of Epilepsy from Large Exome Study

Thu, 03 Oct 2024 00:00:00 +0000

“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.

New Member Alert

Mon, 30 Sep 2024 00:00:00 +0000

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

Bon Voyage!

Wed, 31 Jul 2024 00:00:00 +0000

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

Scholarship Spotlight

Mon, 24 Jun 2024 00:00:00 +0000

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！

Best Poster Award

Thu, 09 May 2024 00:00:00 +0000

Shout-out to Pei-Yu for being selected as one of the 2024 institutional Best Poster awardees

恭喜珮妤的論文海報取得流預所優良海報的佳績

Broadened Genetic Insights on Education

Mon, 15 Jan 2024 00:00:00 +0000

Our collaborative study on the cross-population genetic architecture of education attainment is published in Nature Human Behaviour

This joint study by Taiwan and South Korea researchers presents the first large-scale genome-wide association study (GWAS) of educational attainment, a heritable trait linked to cognitive ability, in East Asian ancestry. Combining this with data from European ancestry, the study reveals a high genetic correlation and similar functional enrichment between populations. Cross-ancestry analysis improved variant fine-mapping and polygenic prediction transferability. The research supports the importance of diverse ancestries to better understand the genetics of educational attainment.

Reference:
Chen, T.-T., Kim, J., Lam, M., Chuang, Y.-F., Chiu, Y.-L., … Feng, Y.-C. A., Lin, Y. F., Myung, W., Chen, C. Y., Won, H. H. (2024). Shared genetic architectures of educational attainment in East Asian and European populations. Nature Human Behaviour, 8(3), 562–575.

Hello, World!

Fri, 29 Dec 2023 00:00:00 +0000

The Feng Lab welcomes its newest (and youngest) member, already trying to lift his head from day one!

Decoding Complex Traits Genetics from Biobanks

Fri, 15 Dec 2023 00:00:00 +0000

Our phenome-wide genetic investigation across Taiwan, Japan, and the UK Biobanks is published in Cell Genomics

In this study, we expanded the scope of genome-wide association studies (GWASs) by analyzing 102,900 individuals from the Taiwan Biobank (TWB), focusing on 36 human quantitative traits. We identified hundreds of novel genetic loci and highlighted the importance of diversifying study populations beyond European ancestries. By comparing genetic architecture across TWB, Biobank Japan, and UK Biobank, we gained valuable insights into the common genetic basis of complex traits in East Asia and demonstrated the effectiveness of cross-population polygenic risk scores in predicting disease risk.

Reference:
Chen, C. Y.*, Chen, T. T., Feng, Y.-C. A.*, Yu, M., Lin, S. C., Longchamps, R., Wang, S. H., Hsu, Y. H., Yang, H. I., Kuo, P. H., Daly, M. J., Chen, W. J., Huang, H., Ge, T., & Lin, Y. F.* (2023). Analysis across Taiwan Biobank, Biobank Japan and UK Biobank identifies hundreds of novel loci for 36 quantitative traits. Cell Genomics, 3(12):100436.

Thanksgiving Cheers

Thu, 23 Nov 2023 00:00:00 +0000

The Feng Lab hosted a Happy Hour on a merry Thanksgiving Day 🦃🎃🫛🥧🍗

New GWAS Method Published

Wed, 15 Nov 2023 00:00:00 +0000

Our collaborative work on the development and validation of a new genome-wide association method is now out in Nature Genetics

We collaborated with University of Queensland scholars to validate and apply their novel genome-wide association study (GWAS) method in three East Asian biobanks (including Japan, South Korea, and Taiwan). This approach corrects for polygenic scores of other chromosomes and uses a 2-step meta-analysis to reduce background variation and enhance statistical power. It identified more genetic loci associated with key traits and biomarkers (such as height and HDL) and improved polygenic predictions, especially for smaller non-European populations.

Reference:
Campos, A. I., Namba, S., Lin, S. C., Nam, K., Sidorenko, J., Wang, H., Kamatani, Y., Biobank Japan Project, Wang, L. H., Lee, S., Lin, Y. F., Feng, Y.-C. A., Okada, Y., Visscher, P., & Yengo, L. (2023). Boosting the power of genome-wide association studies within and across ancestries by using polygenic scores. Nature Genetics, 55(10), 1769–1776.

First Graduate of the Lab

Thu, 05 Oct 2023 00:00:00 +0000

Ling-Hua’s Master’s thesis explored electronic health records in the UK Biobank to study the genetics of treatment resistant depression, revealing a significant polygenic basis and offering insights toward precision psychiatry.

恭喜齡嬅碩士畢業！

Scholarship Spotlight

Tue, 20 Jun 2023 00:00:00 +0000

Congratulations to Mu-Yi Shih and Jeffery Tsai on being awarded the College Student Research Scholarship by the National Science and Technology Council!

恭喜沐儀和哲維獲得國科會大專生專題計畫補助

Taiwan’s Population Genomic Research Resource

Wed, 09 Nov 2022 00:00:00 +0000

“Taiwan Biobank: A rich biomedical research database of the Taiwanese population” published in Cell Genomics

This landmark paper provides a comprehensive genetic characterization of the Taiwan Biobank (TWB), detailing population and familial structure, multi-omics resources, and major discoveries. Together, this demonstrated TWB’s contribution to genetic diversity research, which has since increased its visibility and invited global collaborations.

Reference:
Feng, Y.-C. A.*, Chen, C. Y., Chen, T. T., Kuo, P. H., Hsu, Y. H., Yang, H. I., Chen, W. J., Shen, C. Y., Ge, T., Huang, H., Lin, Y. F.* (2022). Taiwan Biobank: a rich biomedical research database of the Taiwanese population. Cell Genomics, 2(11): 100197.

Dr. Anne Feng Received the Yushan Young Fellow Award

Fri, 05 Aug 2022 00:00:00 +0000

Recognized for research excellence and future academic potential by Taiwan’s Ministry of Education