Sasha Gusev
@sashagusevposts.bsky.social
Statistical geneticist. Associate Prof at Dana-Farber / Harvard Medical School.
www.gusevlab.org
www.gusevlab.org
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...
www.biorxiv.org/content/10.6...
January 9, 2026 at 2:37 PM
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...
www.biorxiv.org/content/10.6...
Reposted by Sasha Gusev
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%:
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%:
January 7, 2026 at 9:20 AM
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%:
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:
January 6, 2026 at 5:52 PM
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:
Reposted by Sasha Gusev
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...
Integrating perturbational screens, eQTL, and GWAS data identifies mediating genes for complex traits
Most current GWAS-eQTL approaches prioritize genes whose mediating effects on complex traits act through cis-regulation, while trans-acting genes remain largely underexplored. Recent perturbational sc...
www.medrxiv.org
January 5, 2026 at 10:27 PM
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:
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...
Integrating perturbational screens, eQTL, and GWAS data identifies mediating genes for complex traits
Most current GWAS-eQTL approaches prioritize genes whose mediating effects on complex traits act through cis-regulation, while trans-acting genes remain largely underexplored. Recent perturbational sc...
www.medrxiv.org
January 6, 2026 at 12:55 AM
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...
open.substack.com/pub/theinfin...
December 29, 2025 at 3:33 AM
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...
open.substack.com/pub/theinfin...
Reposted by Sasha Gusev
If you’ve had qualms about Herasight’s marketing, Sasha Gusev’s (@sashagusevposts.bsky.social) Substack post will give you even more.
Embryo selection company Herasight goes all in on eugenics
...
open.substack.com
December 15, 2025 at 8:07 PM
If you’ve had qualms about Herasight’s marketing, Sasha Gusev’s (@sashagusevposts.bsky.social) Substack post will give you even more.
Reposted by Sasha Gusev
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.
December 14, 2025 at 6:24 PM
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.
Reposted by Sasha Gusev
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.
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.
Embryo selection company Herasight goes all in on eugenics
...
open.substack.com
December 14, 2025 at 4:37 PM
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.
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.
Reposted by Sasha Gusev
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.
ACMG pubmed.ncbi.nlm.nih.gov/38393332/
ASRM pubmed.ncbi.nlm.nih.gov/41309413/
But I'd agree this is nowhere near enough.
December 14, 2025 at 3:31 PM
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.
ACMG pubmed.ncbi.nlm.nih.gov/38393332/
ASRM pubmed.ncbi.nlm.nih.gov/41309413/
But I'd agree this is nowhere near enough.
Reposted by Sasha Gusev
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
I wrote about the bizarre case of Herasight, the embryo selection company going all in on eugenics.
Embryo selection company Herasight goes all in on eugenics
...
open.substack.com
December 14, 2025 at 11:55 AM
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
Reposted by Sasha Gusev
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...
philarchive.org
December 13, 2025 at 9:00 PM
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...
Reposted by Sasha Gusev
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.
Embryo selection company Herasight goes all in on eugenics
...
open.substack.com
December 13, 2025 at 8:52 PM
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.
Embryo selection company Herasight goes all in on eugenics
...
open.substack.com
December 13, 2025 at 8:16 PM
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).
More missing heritability discourse
mutability, twins, and "hereditarianism" versus "nurturism"
open.substack.com
December 8, 2025 at 1:47 AM
I rounded up some of the missing heritability discussions from the past few weeks and got the last word in (for now).
Reposted by Sasha Gusev
I wrote about missing heritability, "missing environmentality," and why I still think twin studies are interesting and valuable: kathrynpaigeharden.substack.com/p/twins-are-...
Twins Are So Much More Interesting Than Heritability Estimates
On starting places, "missing environmentality," and the Waddington landscape of life
kathrynpaigeharden.substack.com
December 4, 2025 at 7:08 PM
I wrote about missing heritability, "missing environmentality," and why I still think twin studies are interesting and valuable: kathrynpaigeharden.substack.com/p/twins-are-...
Reposted by Sasha Gusev
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)
Observational epidemiological studies can mitigate genetic confounding with the genetic relatedness matrix
Observational studies are commonly used in psychology and epidemiology to identify risk factors correlated with health outcomes. However, these studies are vulnerable to confounding when shared geneti...
www.biorxiv.org
December 1, 2025 at 7:09 PM
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.
- 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.
November 30, 2025 at 5:06 PM
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.
- 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
Blog post: A Missing Heritability Update. Three legs and other problems. I follow up on the recent excellent post on the subject by @sashagusevposts.bsky.social. ericturkheimer.substack.com/p/missing-he...
Missing Heritability Revisited
Following up on Sasha
ericturkheimer.substack.com
November 26, 2025 at 12:15 AM
Good context here on the heritability discussion that steps back from dispassionate itemizing
Reposted by Sasha Gusev
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...
A thread... 🧵
www.medrxiv.org/content/10.1...
Interactions with polygenic background impact quantitative traits in the UK Biobank
Association studies have linked many genetic variants to a variety of phenotypes but under-standing the biological mechanisms underlying these signals remains a major challenge. Since genes operate wi...
www.medrxiv.org
November 24, 2025 at 5:13 PM
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...
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!
When genetic analyses are shown to be environmentally confounded the lesson is, uh, look, they just estimate different parameters okay!
I didn’t inhibit my argueing muscle enough. this is actually the right take, it’s eventually a case of “what’s your estimand?”. And it’s all observational, though it needs rigorous models before you can get to an answer (which can be, “these aren’t comparable ever”)
SNP h2 is not even h2 and even with we assume all these to be true, it all breaks up when there's selection and drift.
November 24, 2025 at 2:29 PM
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!
When genetic analyses are shown to be environmentally confounded the lesson is, uh, look, they just estimate different parameters okay!
Reposted by Sasha Gusev
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.
November 21, 2025 at 11:53 PM
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 🧵
The missing heritability question is now (mostly) answered
Not with a bang but with a whimper
theinfinitesimal.substack.com
November 21, 2025 at 10:34 PM
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.
First time on Bsky and first big announcement!
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
Estimation and mapping of the missing heritability of human phenotypes - Nature
WGS data were used from 347,630 individuals with European ancestry in the UK Biobank to obtain high-precision estimates of coding and non-coding rare variant heritability for 34 co...
www.nature.com
November 13, 2025 at 11:41 PM
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.