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...
Interestingly there was no relationship between false signs and local recombination rate or gene constraint, at least in a simple linear model, so something more complicated is going on.
January 6, 2026 at 5:52 PM
Interestingly there was no relationship between false signs and local recombination rate or gene constraint, at least in a simple linear model, so something more complicated is going on.
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:
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.
A handful of other researchers, spanning the ideological gamut from Eric Turkheimer to James Lee, have begun to raise alarm. They are right to do so and the scientific community and the public needs to take notice. /x
December 13, 2025 at 8:16 PM
A handful of other researchers, spanning the ideological gamut from Eric Turkheimer to James Lee, have begun to raise alarm. They are right to do so and the scientific community and the public needs to take notice. /x
Equally strange is the fact that hardly anyone in the genetics community seems to notice or care. Social science genetics organizations that have spent years advocating against genetic essentialism and the abuse of their data have gone silent.
December 13, 2025 at 8:16 PM
Equally strange is the fact that hardly anyone in the genetics community seems to notice or care. Social science genetics organizations that have spent years advocating against genetic essentialism and the abuse of their data have gone silent.
TLDR: An advocate for bog-standard coercive eugenics has now founded a genetic screening company, calls for stigmatization of "unfit" parents in the company ethics white-paper, and proudly tells the world that the company as doing eugenics -- "yes, and it's great!"
December 13, 2025 at 8:16 PM
TLDR: An advocate for bog-standard coercive eugenics has now founded a genetic screening company, calls for stigmatization of "unfit" parents in the company ethics white-paper, and proudly tells the world that the company as doing eugenics -- "yes, and it's great!"
And in case there was any doubt that this was a slip-up, when CBS News recently posted a clip about Herasight and a commenter questioned whether the service was eugenic, Jonathan Anomaly helpfully popped in to reply -- "Yes, and it's great!"
December 13, 2025 at 8:16 PM
And in case there was any doubt that this was a slip-up, when CBS News recently posted a clip about Herasight and a commenter questioned whether the service was eugenic, Jonathan Anomaly helpfully popped in to reply -- "Yes, and it's great!"
Strangely, the authors immediately go on to argue that it actually *is* appropriate to stigmatize would-be parents that are deemed genetically unfit. This is easily the most disturbing argument I've seen in a corporate white paper from a genetics company.
December 13, 2025 at 8:16 PM
Strangely, the authors immediately go on to argue that it actually *is* appropriate to stigmatize would-be parents that are deemed genetically unfit. This is easily the most disturbing argument I've seen in a corporate white paper from a genetics company.
More recently, Herasight (with Anomaly as first author) released a white-paper on the ethics of embryo selection. The white-paper first argues that there is no movement to force couples into screening -- even though Anomaly has advocated exactly that in prior work.
December 13, 2025 at 8:16 PM
More recently, Herasight (with Anomaly as first author) released a white-paper on the ethics of embryo selection. The white-paper first argues that there is no movement to force couples into screening -- even though Anomaly has advocated exactly that in prior work.
Anomaly has been a long time defender of eugenics and billed himself as a "eugenicist" as recently as 2023. In his article Defending Eugenics, he called for a parental licensing scheme to punish parents with "undesirable genetic endowment[s]" and prevent them from reproducing.
December 13, 2025 at 8:16 PM
Anomaly has been a long time defender of eugenics and billed himself as a "eugenicist" as recently as 2023. In his article Defending Eugenics, he called for a parental licensing scheme to punish parents with "undesirable genetic endowment[s]" and prevent them from reproducing.
I do not think embryo selection is a eugenic tool a priori, and have advocated against such knee-jerk labels. But Herasight, via founder and director of communications Jonathan Anomaly, is advocating for eugenics and this should raise alarms.
December 13, 2025 at 8:16 PM
I do not think embryo selection is a eugenic tool a priori, and have advocated against such knee-jerk labels. But Herasight, via founder and director of communications Jonathan Anomaly, is advocating for eugenics and this should raise alarms.
This is a fraught topic so it is good to define some terms. I am following the writing of Galton and the Eugenics Society to define eugenics as an ideology that conditions reproduction on the perceived genetic quality of the parents.
December 13, 2025 at 8:16 PM
This is a fraught topic so it is good to define some terms. I am following the writing of Galton and the Eugenics Society to define eugenics as an ideology that conditions reproduction on the perceived genetic quality of the parents.
Since we were discussing it, I decided to try to access the Longitudinal Study of Aging in Danish Twins sample (LSADT) that had the unusual IQ heritability result. Here's what I found regarding data access:
December 2, 2025 at 3:07 AM
Since we were discussing it, I decided to try to access the Longitudinal Study of Aging in Danish Twins sample (LSADT) that had the unusual IQ heritability result. Here's what I found regarding data access:
Yes, ~15% is the average not captured by common variants between Young and Wainschtein for the traits that had twin estimates. I'm not sure which tweet you're referring to but up-thread I'm talking about ultra-rare burden and ultra-rare coding burden and I believe both numbers are correct:
December 2, 2025 at 2:47 AM
Yes, ~15% is the average not captured by common variants between Young and Wainschtein for the traits that had twin estimates. I'm not sure which tweet you're referring to but up-thread I'm talking about ultra-rare burden and ultra-rare coding burden and I believe both numbers are correct:
I'm not sure what you mean by this. I explain that rare variants contribute a small fraction (~15%) to the total estimated heritability in the same exact paragraph where I talk about ultra-rares. This is in line with GWAS-based estimates of selection implying that the majority of h2 is common.
December 1, 2025 at 5:39 PM
I'm not sure what you mean by this. I explain that rare variants contribute a small fraction (~15%) to the total estimated heritability in the same exact paragraph where I talk about ultra-rares. This is in line with GWAS-based estimates of selection implying that the majority of h2 is common.
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.
to be clear, this isn't a personal comment, it is a comment on the broader posture of the field which has basically been "our glorious causal estimands, their wicked observational correlations" when, in fact, both approaches rely on assumptions that are not justified
November 24, 2025 at 6:21 PM
to be clear, this isn't a personal comment, it is a comment on the broader posture of the field which has basically been "our glorious causal estimands, their wicked observational correlations" when, in fact, both approaches rely on assumptions that are not justified
Thanks! I think there are a couple points here: (1) in the presence of interactions, the heritability estimate from the twin/ACE model will be inflated even over the true broad sense estimate. Fo example, here the true total h2 is 60% but the ACE model estimates 78%:
November 23, 2025 at 9:08 PM
Thanks! I think there are a couple points here: (1) in the presence of interactions, the heritability estimate from the twin/ACE model will be inflated even over the true broad sense estimate. Fo example, here the true total h2 is 60% but the ACE model estimates 78%:
You still haven't articulated the problem with taking an average. We can of course do the same calculation for individual traits and then average that, which produces an even higher twin inflation because of a handful very low WGS-h2 phenotypes. Does this address the concern?
November 23, 2025 at 4:19 PM
You still haven't articulated the problem with taking an average. We can of course do the same calculation for individual traits and then average that, which produces an even higher twin inflation because of a handful very low WGS-h2 phenotypes. Does this address the concern?
Here's Young (2023) [ pmc.ncbi.nlm.nih.gov/articles/PMC... ], citing Kemper (2021), explaining that twin/SR/RDR estimates are all equivalently biased by assortative mating. I think a correction is in order on your claim that this is somehow misleading.
November 23, 2025 at 2:32 PM
Here's Young (2023) [ pmc.ncbi.nlm.nih.gov/articles/PMC... ], citing Kemper (2021), explaining that twin/SR/RDR estimates are all equivalently biased by assortative mating. I think a correction is in order on your claim that this is somehow misleading.
The search now turns towards understanding how inflation impacts the estimates of other studies and, ultimately, what specifically explains the "missing environments". /x
November 21, 2025 at 10:34 PM
The search now turns towards understanding how inflation impacts the estimates of other studies and, ultimately, what specifically explains the "missing environments". /x
We also still do not know why behavioral traits exhibit the largest differences between molecular and twin data. Wainschtein et al. show that environmental confounding is likely still at play (in contrast to anthropometric traits like height).
November 21, 2025 at 10:34 PM
We also still do not know why behavioral traits exhibit the largest differences between molecular and twin data. Wainschtein et al. show that environmental confounding is likely still at play (in contrast to anthropometric traits like height).
What's next? There are still many interesting questions at the trait level. For example, heritability estimates for BMI vary substantially across methods and suggest that more complex environmental interactions may be at play (an echo of prior work: pubmed.ncbi.nlm.nih.gov/28692066/).
November 21, 2025 at 10:34 PM
What's next? There are still many interesting questions at the trait level. For example, heritability estimates for BMI vary substantially across methods and suggest that more complex environmental interactions may be at play (an echo of prior work: pubmed.ncbi.nlm.nih.gov/28692066/).
So there you have it, twin study estimates were greatly inflated, and molecular data sets the record straight. I walk through possible counter-arguments, but ultimately the uncomfortable truth is that genes contribute to traits much less than we always thought.
November 21, 2025 at 10:34 PM
So there you have it, twin study estimates were greatly inflated, and molecular data sets the record straight. I walk through possible counter-arguments, but ultimately the uncomfortable truth is that genes contribute to traits much less than we always thought.