I am excited to share my first paper, our new preprint: www.biorxiv.org/content/10.6... with @arbelharpak.bsky.social and @docedge.bsky.social. Family GWAS provides direct genetic effect estimates and is increasingly important. But how much can we trust these estimates? (1/15)

🧬New from @lukeoconnor.bsky.social & Sella! 📄Principled measures and estimates of trait polygenicity

As I process large gwas summary files I am so thankful, yet again, for tabix. So fast.

Thrilled to see this out. What started out as a chat several years back with @drfejzo.bsky.social about leveraging publicly available data on hyperemesis gravidarum GWAS turned into a wonderful collaboration with April Shu, @mvaudel.bsky.social, @xwww.bsky.social and many others! rdcu.be/fdl9k

Some slides from a recent talk on missing heritability. www.dropbox.com/scl/fi/kvogj...

Gonna be some rad science -- @mollyschumer.bsky.social keynote and a bunch of good talks and posters. And I'll personally pay the registration of anyone who wants to come (it's free).

Differences in evolutionary parameters have important implications for interpreting GWAS results. With the inferred parameters, we reproduced the period when major depression yielded no GWAS discoveries, and we predict that psychiatric disorders will eventually reach higher saturation points. 🧵12/n

This work was done in collaboration with my wonderful mentors @yuvalsim.bsky.social , @jeffspence.github.io , @gs2747.bsky.social , and @jkpritch.bsky.social . doi.org/10.64898/202... 🧵2/n

Monthly median Received to Accepted time (days) at Nature Genetics

Why do schizophrenia GWAS signals look so flat across the genome? In our recent preprint, we explored why psychiatric disorders — and, more broadly, brain-related traits involving the central nervous system — appear to have unusual genetic architectures. 🧵1/n

We invite you to join our seminar at UCSF Mission Bay campus with Hakhamanesh Mostafavi from NYU Grossman School of Medicine humangenetics.ucsf.edu/ihg-seminar-...

It's out! I hope this work encourages folks to move beyond a standard "one variant, one gene" QTL paradigm and consider proxitropic variant effects. Big thanks to the reviewers and editors at @ajhgnews.bsky.social for their help! @sbmontgom.bsky.social www.sciencedirect.com/science/arti...

Excited to share our new preprint from the @arbelharpak.bsky.social Lab! How do recruitment into genetic studies and study characteristics impact what we infer about the genetic bases of traits, and what are the consequences? (1/21) www.biorxiv.org/content/10.6...

If you like larger sample sizes, then do check out our reprocessed and fine mapped cis-eQTLs and cis-sQTLs (leafCutter and MAJIQ!) from the INTERVAL cohort (whole blood, n up to 4,729)! zenodo.org/records/1795... These will be on the eQTL Catalogue FTP soon as well. cc @yosephbarash.bsky.social

We used a similar design in this paper: www.sciencedirect.com/science/arti... Found that in cis-MR with multiple colocalising instruments (i.e. multiple indepdent signals colocalise between eQTL and pQTL traits) sign concordance was around 95%:

Your numbers after stringent colocalization seem quite consistent with theirs (tagging @nikhilmilind.dev @jkpritch.bsky.social) . Colocalization is clearly needed, but it kills recall and that's a difficult thing to get around with standard sample sizes...

Clever use of proteomic data to stress-test TWAS and QTL colocalization methods, revealing a high false sign rate. This hypothesis about high-LD and cross-tissue confounding is particularly interesting:

Happy to share our new preprint from @sashagusevposts.bsky.social and @nmancuso.bsky.social labs! We introduce Mr. PEG, a framework integrating perturbational screens, eQTL, and GWAS data to identify mediating genes for complex traits. (1/n) www.medrxiv.org/content/10.6...

New method from our group for identifying disease-mediating genes using perturb-seq, eQTL, and GWAS data. Check out the thread:

New preprint alert: we use sign errors as a test of how well TWAS works. Very worryingly we find that TWAS gets the sign wrong around 1/3 of the time (compared to 50% for pure guessing). You can read more about our analysis here, and what we think is going on 👇

How well does TWAS estimate a gene’s direction of effect on a trait? We think of this as an important stress-test for the accuracy of TWAS. In a new pre-print, we find that TWAS gets the sign wrong around 20-30% of the time! doi.org/10.64898/202... 1/n

I'm just delighted to announce our new preprint on genome-scale perturb-seq in CD4+ T cells. We learned both general lessons about the power of perturb-seq, and specific lessons about T cell biology. Led by amazing postdocs Emma Dann and Ronghui Zhu, with my wonderful collaborator Alex Marson.

This is only the beginning: with the help from lattice team @biohub.org, we made all the data available. We hope this dataset will be a foundational resource for systems immunology, human genetics, "virtual cell" modeling efforts, and immunotherapy development.

Together with @ronghuizhu.bsky.social, we are thrilled to present our new perturb-seq study of 22M primary CD4+ T cells, across donors and timepoints – the result of a decade-long collaboration between the Marson @marsonlab.bsky.social and Pritchard @jkpritch.bsky.social labs 🧵 tinyurl.com/gwt2025

Happy to highlight an essay I wrote together with @marcdemanuel.bsky.social, @natanaels.bsky.social and Anastasia Stolyarova, trying to think through what sets the mutation rate of a cell type in an animal species: www.biorxiv.org/content/10.6... 1/n

We wrote the Strain on scientific publishing to highlight the problems of time & trust. With a fantastic group of co-authors, we present The Drain of Scientific Publishing: a 🧵 1/n Drain: arxiv.org/abs/2511.04820 Strain: direct.mit.edu/qss/article/... Oligopoly: direct.mit.edu/qss/article/...

High false sign rates in transcriptome-wide association studies https://www.biorxiv.org/content/10.64898/2025.12.19.695550v1

Important piece thinking through what eugenics actually is and how this qualifies. It's not lost on me that these companies are primarily men telling women how to responsibly reproduce. The marketing/examples are telling. It's part of a larger movement around control & should be treated seriously.

I wrote about the bizarre case of Herasight, the embryo selection company going all in on eugenics.

As a (to me very enjoyable) part of this paper, we worked out what mutation-selection balance looks like in finite populations with varying degrees of inbreeding.

Our latest preprint revisits the classic model of mutation-selection balance. Do human recessive genes fit Haldane's 100-year old model? This work is by the wonderful @jonj-udd.bsky.social, and co-mentored by @jeffspence.github.io www.biorxiv.org/content/10.6...

GWAS has been an incredible discovery tool for human genetics: it regularly identifies *causal* links from 1000s of SNPs to any given trait. But mechanistic interpretation is usually difficult. Our latest work on causal models for this is out yesterday: www.nature.com/articles/s41... A short🧵:

Thank you Alex! Excited to see our paper published in @nature.com ! Huge thanks to @jeffspence.github.io , @tkyzeng.bsky.social , @emmamarydann.bsky.social, @nikhilmilind.dev, @marsonlab.bsky.social, @jkpritch.bsky.social, and all the members of the Pritchard and Marson labs for your enormous help!

Our latest collaboration with @jkpritch.bsky.social – led by joint post-doc Mineto Ota – is in @nature.com today: www.nature.com/articles/s41...

BAPG 2025 was a blast. Looking forward to seeing folks in Davis in Spring 2026! bapg2025.github.io/bapg2025stan...

Excited to share our new FinnGen single-nucleus multiome preprint! 🧬 We profiled ~10M PBMCs (snRNA-seq + snATAC-seq) from 1,108 Finnish donors to map how genetic variants drive complex disease through chromatin and gene regulation 🧵👇 🔗 Link: www.medrxiv.org/content/10.1...

As promised, a longer thread on what I consider to be some of the most interesting and important contributions of this paper (1/10)

Excited to share work from my postdoc with @docedge.bsky.social and collaborators Matt Pennell and @jgschraiber.bsky.social, newly out over the weekend: www.biorxiv.org/content/10.1... (1/6)

The last work of my PhD is finally out: www.pnas.org/doi/10.1073/...! This work is about accurately estimating branch length in the Ancestral Recombination Graph (ARG), which is achieved by a really simple framework with minimal assumptions. (1/n)

I wrote a little bit about the "missing heritability" question and several recent studies that have brought it to a close. A short 🧵

We have 115 people signed up already for BAPG! Great representation across career stages too. If you want to attend don't forget to sign up. It is free but required. @sophiejwalton.bsky.social and I are looking through the wonderful talk submissions and will announce the talks shortly. Stay tuned!

@hakha.bsky.social and I wrote a Research Briefing (with a lay summary + "behind the scenes") of our paper on how genes are prioritized by GWAS and rare variant burden tests. 🧬🧪 www.nature.com/articles/d41...

Looking forward to presenting our work on characterizing eqtl architecture across ancestors and cells tomorrow at the Evolgenome seminar! Huge thanks for the invite @lindakachuri.bsky.social

I am so excited to share our project with you! We find prokaryotic proteases activate toxic enzymes and pores as a modular strategy in phage defense. We studied four fascinating protease-toxin pairs that are abundant across bacterial genomes: www.biorxiv.org/content/10.1...

My center at NYU SoM is hiring an Assistant/Associate Professor in human genetics and genomics. It's a wonderful place to do science. Please apply or pass along. apply.interfolio.com/177375

SAVE THE DATE: the yearly NY Population Genetics meeting will be back on March 9 2026, generously hosted by the @simonsfoundation.org. Details to follow. Please RT.

An empirical approach to evaluating the prevalence of long-lived balancing selection in humans--and important limitations. Work by @hannahmm.bsky.social

Happy to see this paper from my time with @spicybotrytis.bsky.social out in @theplantcell.bsky.social! Amanda, a fantastic PhD student with Dan, led this "phylo-functional" work & uncovered complex duplication & loss of a glucosinolate gene across the Brassicaceae affecting enantiomeric specificity

Really cool paper that changed the way I think about what GWAS and Burden tests are doing, and also basically made me pleiotropy-pilled

Excited to share our latest work on the factors that determine what genes we find (and don't find!) in GWAS and burden tests. We describe a critical concept that we call *specificity*. Led by Jeff Spence and Hakhamanesh Mostafavi: