I want to shout out @aneil-agrawal.bsky.social, @jmillercole.bsky.social and the @arbelharpak.bsky.social lab for helpful feedback and discussion! I also sincerely thank our AJHG editors and reviewers who gave me an overwhelmingly positive (and dare I say fun) first publication experience! (14/14)

This project has been an incredibly rewarding and educational experience for me, and I’m thankful to my coauthor Changde Cheng and my advisors Mark Kirkpatrick and @arbelharpak.bsky.social for their work, thoughts, and guidance throughout! (13/14)

We conclude that while causal relationships between SDS and sex-differential gene expression in humans remain plausible, they are yet to be fully elucidated. We are excited to continue exploring how signals and drivers of genome-wide SDS may be detected. (12/14)

We also discuss how other factors may lead to a lack of signal. For example, sex-differential expression driving SDS may be rare. Or sex-differential expression may be related to past but not current SDS. (11/14)

We hypothesize eQTL ascertainment bias, as explored by @hakha.bsky.social et al. could contribute to the lack of signal: eQTL discovery is biased against sites under strong selection, weakening a relationship between FST and sex-differential expression (10/14)

doi.org/10.1038/s415...

However, work by Carrie Zhu, @jmillercole.bsky.social , @filipruzicka.bsky.social, and others have shown pervasive genome-wide signals of SDS using other methods. (10/14)

doi.org/10.1016/j.xg...
doi.org/10.1073/pnas...
doi.org/10.1371/jour...

Our results indicate that, even if a relationship between SDS and sex-differential expression exists, its signals are difficult to model and detect. (9/14)

Alas, across 34 human tissues, we find no evidence for a general, genome-wide relationship between sex-differential expression and SDS. (8/14)

We next re-investigate the relationship between between-sex FST and sex-differential expression with new and improved data (thanks to 2025 > 2016) and statistical model. (7/14)

We thus revisit the interpretation that a Twin Peaks pattern suggests sex-differential gene expression drives SDS. We find 21.2% of empirical null samples result in Twin Peaks, so Twin Peaks is consistent with no relationship between sex-differential expression and SDS. (6/14)

In our manuscript, we found caveats to the Twin Peaks theoretical expectation. (5/14)

Cheng and Kirkpatrick explicitly modeled the relationship between SDS and sex-differential expression and describe a “Twin Peaks” pattern which arises when sex-differential expression drives SDS. (4/14)

doi.org/10.1371/jour...

Previous work has observed a relationship between SDS and sex differences in gene expression. However, these results have been hotly contested. (3/14)

Sex-differential selection (SDS) occurs when allelic fitness effects differ between males and females. SDS acting on viability will lead to differences in allele frequencies between the sexes, quantified using between-sex FST. (2/14)

I am excited to share the first first-author paper of my PhD describing work with Changde Cheng, Mark Kirkpatrick and @arbelharpak.bsky.social has been published at AJHG! We ask if sex-differential gene expression drives sex-differential selection in humans. (1/14)

www.cell.com/ajhg/fulltex...