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 Cassie Spracklen (@Cnspracklen) to discuss her paper A cross-ancestry genome-wide meta-analysis, fine-mapping, and gene prioritization approach to characterize the genetic architecture of adiponectin.
HGGA: What motivated you to start working on this project?
CS: In order to move from genome-wide associated loci toward potentially effective clinical and therapeutic targets, we need to identify which target/effector gene(s) the associate variants are being modulated. There are multiple methods that currently exist that can be used to prioritize these effector genes, but they can often give conflicting or inconsistent results. So we set out to create an approach, GPScore, that combines evidence from 11 methods together with physical distance to nearby transcription start sites as a way to integrate multiple lines of evidence together.
HGGA: What about this paper/project most excites you?
CS: In this paper, the GPScore approach prioritized 30 target/effector genes for 22 adiponectin-associated loci. At loci where we believe to already know the effector gene, the approach successfully prioritized these genes (e.g., ADIPOQ, CDH13). At many of the novel adiponectin loci and for loci where the effector gene is not already known, the genes prioritized are strong functional candidates based on existing literature. Functional association networks of the prioritized genes also revealed underlying pathways and networks centered around insulin, adiponectin, and related traits, providing further support that our combinatory approach is working well to prioritize effector genes for further investigation.
HGGA: What do you hope is the impact of this work on the human genetics community?
CS: After more than 15 years of genome-wide association studies, there is an urgent need to translate the findings into clinical and public health-relevant practice. However, the task of identifying putative causal variants and effector genes can be daunting. GPScore was designed to be customizable so that researchers can use the most applicable input files for their phenotype(s). We hope that others in the human genetics community will find GPScore to be a helpful approach to identify candidate effector genes for additional interrogation.
HGGA: What are some of the biggest challenges you’ve faced as a young scientist?
CS: I love the collaborative nature of human genetics and am grateful for the collaborations that I have established all over the world. However, this means that I often keep an unusual schedule, with calls scheduled and emails sent at very odd hours!
HGGA: And for fun, what is one of the most fascinating things in genetics you’ve learned about in the past year or so?
CS: In the last year or so, I have become interested in learning the dark and troubling history of genetics, particularly as it pertains to eugenics, population/reproductive control, and immigration. I think we have a lot to learn about how the genetic discoveries and advancements we are making now are being perceived by the public and those outside of the field, along with all of the ELSI considerations we often overlook.