Posted By: The American Journal of Human Genetics, AJHG
Each month, the editors of The American Journal of Human Genetics interview an author of a recently published paper. This month, we check in with Kate (@itskatelawrence.bsky.social) to discuss her recent paper, “Focus on single-gene effects limits discovery and interpretation of complex-trait-associated variants.“
AJHG: What motivated you to start working on this project?
KL: We kept running into GWAS loci where the whole “one variant, one gene” story felt incomplete. You’d fine-map to a regulatory region sitting between multiple genes, and everyone would argue about which one was “the” causal gene—but what if that was the wrong question? We knew from CRISPRi work that regulatory elements often link to multiple nearby genes, yet QTL methods were still testing genes one at a time. That disconnect motivated us to ask: what if we’re missing regulatory signals because we’re testing the wrong unit? That question led to pcQTLs.
AJHG: What about the paper/project most excites you?
KL: Although the new GWAS colocalization discoveries are exciting, I’m most excited by the conceptual shift. Introducing “allelic proxitropy” gives us language and a framework to describe variants that impact the regulation of multiple, nearby genes, which we hope will change how people think about causal mechanisms at noncoding loci.
AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?
KL: This work highlights the importance of multi-gene regulatory mechanisms and underscores how moving beyond a “one variant, one gene” paradigm can provide a more complete picture of the complexities of non-coding variation and its impacts on complex traits. We hope that the use of pcQTls or other multi-gene frameworks in the human genetics community will lead to a more nuanced and complete view of the impact of genetic regulation.
AJHG: What advice do you have for trainees/young scientists?
KL: I will pass on advice given to me when I was an undergrad – there are as many ways to be a success at science as there are successful scientists. This advice stuck with me; I think it has encouraged me to be deliberate in choosing my own path, and not to worry so much about the mold of a “typical” scientist.
AJHG: And for fun, tell us something about your life outside of the lab.
KL: For several years, I raced mountain bikes in the Enduro World Series. Now I ride for fun, not professionally, but I still try to train for a few races a year!
Kate (Kathryn) Lawrence is a PhD Candidate at Stanford University.