I used Claude Opus 4.5/4.6 (and a bit of Codex GPT-5.3) to port edgeR to Python. See edgePython github.com/pachterlab/e... This allowed me to develop a single-cell DE method that extends NEBULA with edgeR Empirical Bayes. All in one week. Details in doi.org/10.64898/202...

Gave Codex an old R simulation I had lying around and it very adeptly turned it into an interactive web app with tunable parameters and visualizations. sashagusev.github.io/Stabilizing-...

Another Claude project: a static site that pulls in GWAS SNP data from ensemble, multiple public biobanks, open targets, gtex, eqtl catalog, and OMIM. sashagusev.github.io/gwas_lookup/

Quick Claude Code project: download movie showtimes from Fandango, upload to this site, select some movies, and it will generate a marathon schedule. For example, you could go see F1, MELANIA, Iron Lung, and Mercy at the AMC Boston Commons -- what a treat! Took <1hr to prompt ...

Great piece in the NYtimes with quotes from @stairwaytokevin.bsky.social and @sashagusevposts.bsky.social. The misuse of NIH datasets with sensitive personal information for racist aims should be concerning for anybody interested in scientific integrity. www.nytimes.com/2026/01/24/u...

Interesting new multi-population aDNA selection scan from Colbran, Terhorst, Mathieson. Loci that are estimated to be under selection in one population also show enrichment in other populations, consistent with parallel or pre-split selection. www.biorxiv.org/content/10.6...

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%:

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:

Jonathan Anomaly responds in a long comment to my post criticizing his writing on eugenics and that of his company Herasight. He argues against several specific points and I encourage reading it in full. open.substack.com/pub/theinfin...

If you’ve had qualms about Herasight’s marketing, Sasha Gusev’s (@sashagusevposts.bsky.social) Substack post will give you even more.

Yes, these are good statements but they mostly leave the broader implications for other people to sort out. A point that I think has been under-appreciated is that these companies have a direct commercial incentive to create stigma around not using the technology, and they are aggressively doing so.

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.

To be fair, there have been a couple of articles published from professional organisations pushing back against PGT-P and embryo selection: ACMG pubmed.ncbi.nlm.nih.gov/38393332/ ASRM pubmed.ncbi.nlm.nih.gov/41309413/ But I'd agree this is nowhere near enough.

This is an excellent piece: embryo selection isn’t necessarily eugenics but the founder of Herasight is openly advocating for eugenics, largely without pushback from academics or academic societies

Like, “Defending eugenics” is an absolutely bonkers title for a paper and the author list is a mix of “people you’d totally expect to write this article” and “people who should know better”. Either way an actual scholar of eugenics took them to school philarchive.org/archive/WILE...

As usual the science is questionable, but Anomaly is a particularly nasty and intellectually/ethically problematic person at the helm

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

I rounded up some of the missing heritability discussions from the past few weeks and got the last word in (for now).

I wrote about missing heritability, "missing environmentality," and why I still think twin studies are interesting and valuable: kathrynpaigeharden.substack.com/p/twins-are-...

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)

Massive single-cell study by Kanai et al (www.medrxiv.org/content/10.1...): - Once statistical power is high, constrained genes have more (though weaker) eQTLs. - Chromatin-QTLs near constrained genes have "normal" effect sizes, colocalize more with disease, but exhibit attenuated peak-gene effects.

Good context here on the heritability discussion that steps back from dispassionate itemizing

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...

When non-genetic, correlative analyses are shown to be genetically confounded, the lesson is that we shouldn't use them to draw any causal conclusions. When genetic analyses are shown to be environmentally confounded the lesson is, uh, look, they just estimate different parameters okay!

Some history of science grad student is going to have one hell of a dissertation about how Arthur Jensen wrecked two disciplines for half a century.

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

Nice! Whole-genome heritability estimates in the UK Biobank. Average WGS-h2 was 26%, with 21% common and 5% rare. Broadly aligns with recent sib-reg and RDR estimates.

Excited to share this preprint from first author Jon Rosen, a postdoctoral fellow in the @klmohlke.bsky.social lab and my lab. We examine eQTL study sample size and how this affects signal discovery and rates of colocalization with GWAS. www.biorxiv.org/content/10.1...

Very happy to be back in Boston for #ASHG25🧬 this time as a PI! Very proud of my stellar PhD student Jiawei who’s giving a platform talk on her work quantifying influences of genetic ancestry and the environment on tumor somatic alterations and survival. 🗓️ Wed Oct 15 11:15AM

In 2018, Charles Murray challenged me to a bet: "We will understand IQ genetically—I think most of the picture will have been filled in by 2025—there will still be blanks—but we’ll know basically what’s going on." It's now 2025, and I claim a win. I write about it in The Atlantic.

Massive sibling regression study finds that human traits are largely environmentally driven (average heritability = 0.3)

Interesting evidence for genetics explaining disparities in T2D. Previous work identified a Neanderthal introgressed haplotype common to Native American ancestry with a large effect on T2D (pmc.ncbi.nlm.nih.gov/articles/PMC...). Wonder if there's power to look at archaic admixture here.

Brilliant paper by Visscher et al. Populations differ in traits/disease burden. Are these differences due to genetics? Comparing single variants or polygenic scores between populations is biased due to environmental confounders correlated with the variants. 1/3 www.medrxiv.org/content/10.1...

Delighted to see this paper with @anaignatieva.bsky.social now published in Genetics! academic.oup.com/genetics/adv... We tackle a thorny issue arising in statistical tests for genetic interactions (epistasis) using ancestral recombination graphs (ARGs)... 🧵

Excited to share our latest manuscript, "Exposure accumulation drives age-dependent disease architectures and polygenic risk scores," led by Xilin Jiang: www.medrxiv.org/content/10.1... I am attempting an explainer thread for the first time here: (I am usually too exhausted to post one)

I wrote about a rare genetic variant (a CNV) that appears to reduce the risk of schizophrenia diagnosis by ~5x, and why that's not as unambigously amazing as it sounds, but potentially still a pretty big deal.

Great mini thread here on lessons for GxG and GxE from non-human organisms:

Nice blog and good to see this also from the twins/shared environment side. We (with my colleagues in @wittbrodtlab.bsky.social) have tried to tackle the non-additive in experimental settings (in medaka fish) which we can map to human (as the medaka fish are "wild") www.biorxiv.org/content/10.1...

🧵 on cool choices of image headers (and titles) all from @sashagusevposts.bsky.social's Substack 🔗 at the end 'Beneath the surface of the sum' Genetic interactions may look like the thing they deviate from Interaction (1964) by Julian Stanczak

I wrote about gene-gene interactions (epistasis) and the implications for heritability, trait definitions, natural selection, and therapeutic interventions. Biology is clearly full of causal interactions, so why don't we see them in the data? A 🧵:

The twin/family studies were not clear whether it was dominance vs. epistasis vs. some other sort of nonadditivity. Dominance was just the easiest to model. We can now estimate dominance SNP h2 but can’t obtain an estimate of epistatic SNP h2. Assimilation/contrast effects may also be at play.

While I am not entirely convinced this is “real” and not some psychometric equivalent of a vowel shift (and PRS could help find out a bit I think) this it is relevant:

One of the largest twin studies of personality anticipated massive non-additive dominance/epistasis components. These have not materialized with modern data for *any trait*, no one knows why, and the entire set of findings has apparently been memory-holed.

Decrease in phenotype by intervening on additive or epistatic mechanisms in the presence of low (left) or high (right) epistasis. Red lines indicate an increase in the phenotype when a decrease was intended.

Popgen, day7: single-locus selection models. Allele frequency change is faster at intermediate frequencies! Fixation takes longer in larger pops! And a bit more from yesterday on MK (asymptotic MK test is cool!)

Any discussion of embryo selection should probably start with the description of IVF in this piece, to at least be connected to some aspect of tangiable reality.