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 Nikolas (X; BlueSky; LinkedIn) to discuss his recent paper “Individuals who deviate from polygenic expectation are enriched for damaging variants in genes linked to rare disease.“
AJHG: What motivated you to start working on this project?
NB: I think the topic of outliers is really interesting! At the start of my PhD, there were two ways I was thinking about outliers: people who have extreme observed values, and people who have extremely different observed values relative to expectation. In genetics, using common-variant polygenic scores is a classic way to estimate someone’s “expected” phenotype, so naturally we thought: what if rare variants are driving the outliers with “unexpected” phenotypes?
AJHG: What about the paper/project most excites you?
NB: I think it’s really satisfying that we’re able to tie together rare and common variants, continuous and dichotomous traits, all into one unified model of liability. And that our work is relevant to both common disease and rare genetic disorders!
AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?
NB: For clinical geneticists, our work implies that using deviation from common-variant polygenic scores could be a powerful strategy to screen individuals for rare genetic disorders. For statistical geneticists looking for therapeutic targets, our work suggests that there may be interesting gene associations that can only be uncovered by first accounting for common-variant effects. And for everyone else in the genetics community, our work highlights the importance of considering both common and rare-variant genetic architecture in complex disease.
AJHG: What advice do you have for trainees/young scientists?
NB: Read more review papers! It’s a great way to get historical perspective.
AJHG: And for fun, tell us something about your life outside of the lab.
NB: I love to row. And it’s easy for me to explain my outlier research to fellow rowers because it’s a sport that selects for extreme height!
Nikolas Baya, PhD, is a Postdoctoral Fellow at Massachusetts General Hospital and the Broad Institute of MIT and Harvard.