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.

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

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 guess the preprint came out in 2024 but it was published this year so I'll say this paper from @jeffspence.github.io and @hakha.bsky.social which is probably the paper that pleiotropy-pilled me the most. Really got me to think about what GWAS means www.nature.com/articles/s41...

My lab is recruiting postdocs in AI/ML for genetics & genomics through the Malone Postdoctoral Fellows program. Apply by Jan 30! Lots of other great labs across the Malone Center as well.

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🧵:

After time in the Bay Area, I’ve started a new role as Lecturer in the Department of Allergy and Rheumatology at the University of Tokyo. We’re the group of clinicians who see patients with autoimmune diseases, while researching new treatments and patient stratification. (continued)

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!

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

It was a total pleasure to work with @roshnipatel.bsky.social on this, who really led the charge in all respects. Anyone interested in learning about the intersection of population genetics and statistical genetics should check out her new lab in Oregon!

Excited to share a preprint of my PhD project looking at interactions between SNPs and polygenic scores in the UK Biobank! A thread... 🧵 www.medrxiv.org/content/10.1...

#OnThisDay in 1859, Charles Darwin's On the Origin of Species was first published. Much of the original manuscript was used as scrap paper by Darwin's children. On the back of this painting of a house is an original manuscript page from Origin! #CambridgeUniversityLibrary (DAR 185)

@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...

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.

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

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

Very excited for our paper in @nature.com on what genes association studies discover and why. It was a privilege to work closely with @jeffspence.github.io, @jkpritch.bsky.social, and our collaborators.

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:

How does life evolve to adapt to modern cities? Out now in Science, my PhD work with @lindymcbr.bsky.social uncovers the ancient origin of the “London Underground mosquito” – one of the most iconic examples of urban adaptation. 🧵(1/n) @science.org www.science.org/doi/10.1126/science.ady4515

Why do complex traits differ in their genetic architecture? In our new PLOS Biology paper, we will try to convince you that two simple scaling laws drive differences in the number, effect sizes and frequencies of causal variants affecting complex traits. Thread: journals.plos.org/plosbiology/...

I’ll be attending #ASHG25! I’m currently hiring for (i) a Senior Research Scientist or (ii) a Postdoc position in my lab. If you’re interested, please reach out to arrange a time to meet and discuss.

Bittersweet to be leaving @docedge.bsky.social after a wonderful postdoc, but excited to share that I'm joining @uoregon.bsky.social next month as an Assistant Professor in the Department of Data Science.

The 2026 Probabilistic Modeling in Genomics (ProbGen) meeting will be held at UC Berkeley, March 25-28, 2026. We have an amazing list of keynote speakers and session chairs: probgen2026.github.io Please help spread the news.

I'm thrilled that my lab at NYU is now supported by an NIH MIRA grant! I'm looking to hire 1-2 senior lab members (outstanding postdoc candidates or experienced staff scientists) with expertise in computational or statistical methods in human genetics or genomics. Please share!

A brief musical note: I’m very excited to share that my brilliant wife, a pianist and composer, has just released her debut album featuring works by Iranian women composers, including one of her own. Here is the link in case you’d like to take a listen: www.navonarecords.com/catalog/nv67...

Staff scientist position (computational): I am looking for a computational scientist to join my genomics lab at Stanford. They should have an outstanding skillset in ML/statistical methods for genomic applications, postdoc experience and a strong publication record. #sciencejobs

It was fun writing this short piece on the omnigenic model. Sharing it here, though it's a painful time as my family, along with millions of others, is at risk in Iran and the region.

Thanks to everybody who chimed in! I arrived at the conclusion that (1) there's a lot of interesting stuff about interactions and (2) the figure I was looking for does not exist. So, I made it myself! Here's a simple illustration of how to control for confounding in interactions:>

Amidst all the terrible and terrifying news, so lovely to hear of @jkpritch.bsky.social's election to the National Academy of Sciences. Congratulations!

I've been singing with the Bronx County Chorus since 2015. It's a beautiful, intergenerational community bringing free music to the Bronx since the 1930s. With grants shrinking, they now need support to keep going. If you can, please consider helping: www.gofundme.com/f/support-th...

Posting on behalf of Shamil Sunyaev: Eimear(Vice Chair) and I (Chair) are organizing the 2025 Gordon Research Conference (GRC) on Human Genetics and Genomics, which will be held on July 6-11, 2025 in beautiful University of Southern Maine, Portland, Maine.

A really nice paper by @drghawkes.bsky.social et al. argues that rare and common genetic associations converge on the same genes. While this seems at odds with our recent work about how burden tests and GWAS prioritize different genes, our results agree (🧬🧪🧵 1/6) www.biorxiv.org/content/10.1...

One month to go until the CSHL Biology of Genomes abstract deadline! My all-time fav meeting, and one of the few covering genomics broadly. We have a ✨🤩 lineup of speakers, but it's the abstract talks & posters that really make the meeting - send us your best work! meetings.cshl.edu/meetings.asp...

Think of a polygenic score you care about. Are direct genetic effects driving variation among people in this predictor? Or perhaps other, confounding factors? We at the @arbelharpak.bsky.social & @docedge.bsky.social Labs developed a method to tackle this question. [1/n]

The distribution of highly deleterious variants across human ancestry groups https://www.biorxiv.org/content/10.1101/2025.01.31.635988v1

Our paper “A genome-wide atlas of human cell morphology” is finally out today in @naturemethods.bsky.social ! www.nature.com/articles/s41... (I tweeted about our preprint in 2023 over at the bad place, but deactivated my account, so here we go again!)

How population stratification makes environments look like genes. A short 🧵:

Modern GWAS can identify 1000s of significant hits but it can be hard to turn this into biological insight. What key cellular functions link genetic variation to disease? I'm very excited to present our new work combining associations and Perturb-seq to build interpretable causal graphs! A 🧵

Very excited about this new work from our lab! Explainer thread coming soon @minetoota.bsky.social

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...

Our daughter's wonderful teacher and her family lost everything in the Eaton fire. If you can spare a few dollars to help out, I would be grateful www.gofundme.com/f/help-the-l...

Now available as preprint: The ENCODE 4 expanded registry of regulatory elements - 2.35M 🧍 human cCREs - 927k 🐭 mouse cCREs www.biorxiv.org/content/10.1... Led by @moorejille.bsky.social, this preprint summarizes data and analyses generated by hundreds of contributors across ENCODE 4

I’m thrilled to join #GENETICS as an associate editor!

I truly think teaching the complexities of inheritance to demonstrate that it’s more than simple Mendelian genetics that explains traits would help reduce the number of people who believe in genetic determinism. Disease would be a fruitful start to that but it can be applied to a variety of traits

The secret sauce for starting a new lab is to set up the right kind of culture; one that best enables innovative science with its “enthusiasm, lucid criticism, nonconformism, and friendship” (Francois Jacob)

Very cool paper. Something I have always been curious about is the extent to which rare burden trait-specific genes are themselves regulators of pleiotropic genes. I.e. the genes on the bottom are TFs for the variants on the top.

A great paper and a great thread! One point that I partcularly liked was this one: "In particular, [GWAS] variants can be trait specific in two ways: they can either affect a trait-specific gene or affect a pleiotropic gene in a context-specific manner."

Excited to share our latest work! We find that common-variant GWAS and rare-variant burden tests prioritize genes in fundamentally different ways, with important implications. Check out Jeff’s excellent thread below👇

Most of the talks from our Oct meeting are now online, with a few more to come: www.precisionmedicine.columbia.edu/videos