Posted By: HGG Advances
Each month, the editors of Human Genetics and Genomics Advances interview an early-career researcher who has published work in the journal. This month, we check in with Wan-Ping Lee, PhD, to discuss their paper, “A specialized reference panel with structural variants integration for improving genotype imputation in Alzheimer’s disease and related dementias.”
HGGA: What motivated you to start working on this project?
Most genomic research has focused on individuals of European ancestry and has commonly used imputation panels that contain more European haplotypes, leading to poorer accuracy in other ancestries. In addition, standard panels are largely disease-agnostic, whereas ours is built from Alzheimer’s disease (AD) genomes, improving the imputation of disease-related rare variants. Our panel also includes structural variants (SVs), enabling the imputation of SVs alongside single-nucleotide variants (SNVs)/indels.
HGGA: What about this paper/project most excites you?
Seeing clear accuracy gains, especially precise SV imputation, was both encouraging and exciting. Early on, we heard that existing panels were “good enough.” Completing this project shows that even incremental, well-validated improvements can materially advance discovery in human genetics.
HGGA: What do you hope the impact of this work will be for the human genetics community?
We hope the panel enables researchers to study disease-related rare variants and SVs more effectively in AD and beyond. We also aim for others to reuse our methods/pipelines to construct disease-specific, ancestry-inclusive panels for additional traits and disorders.
HGGA: What are some of the biggest challenges you’ve faced as a young scientist?
I’m fortunate to have strong mentorship. A key challenge as an early-career scientist is building adoption for new tools in areas with established solutions. Rigorous benchmarking, transparency, and clear communication have been essential for convincing the community of the value added.
HGGA: And for fun, what is one of the most fascinating things in genetics you’ve learned about in the past year or so?
Gene editing continues to advance patient care. Notably, clinicians used a prime editor to treat a teenager with a rare immunodeficiency; early readouts showed improved immune-cell function. As a “search-and-replace” editor that avoids double-strand breaks, prime editing represents a meaningful safety and versatility step beyond classic CRISPR nucleases.
Wan-Ping Lee, PhD, is a Research Assistant Professor in the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania.