Sasha Gusev

@sashagusevposts.bsky.social

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Statistical geneticist. Associate Prof at Dana-Farber / Harvard Medical School.

www.gusevlab.org

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I wrote about the knowns and unknowns around polygenic embryo selection, expanding on a previous post about genetic prediction of IQ. open.substack.com/pub/theinfin...

Science fictions are outpacing science facts for polygenic embryo selectionopen.substack.com If you thought prediction in adults was complicated, you haven’t seen the half of it!

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Sasha Gusev

I'm late to the party, but excellent stuff. From the beginning, IQ-GWAS has defended itself by wishcasting the future. Wait till we have bigger samples, better methods, what are you going to say when we can predict 40% of the variance? But the future arrived and it didn't happen.

I wrote about the latest attempt to sell genetic IQ prediction and why it is snake oil. A short 🧵: theinfinitesimal.substack.com/p/genomic-pr...

Genomic prediction of IQ is modern snake oiltheinfinitesimal.substack.com Predicting IQ from genetics is inaccurate, confounded, and sows confusion about genetic research.

I'm surprised this paper has not generated more discussion. In a single cohort (so no measurement differences): "For 37 behaviour problem measures, the average twin heritability was 0.52, whereas the average SNP heritability was just 0.06". What's going on? www.nature.com/articles/s41...

Childhood behaviour problems show the greatest gap between DNA-based and twin heritability - Translational Psychiatrywww.nature.com Translational Psychiatry - Childhood behaviour problems show the greatest gap between DNA-based and twin heritability

I wrote about the latest attempt to sell genetic IQ prediction and why it is snake oil. A short 🧵: theinfinitesimal.substack.com/p/genomic-pr...

Genomic prediction of IQ is modern snake oiltheinfinitesimal.substack.com Predicting IQ from genetics is inaccurate, confounded, and sows confusion about genetic research.

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Sasha Gusev

Richard Lynn was a pillar of 20th-century scientific racism. His magnum opus was a database of "national IQs", a menagerie of unrepresentative IQ studies with no explicit criteria for inclusion except that the results show a low IQ for Africans. This should be an open-and-shut case for retraction.

Journals that published Richard Lynn's racist 'research' articles should retract themwww.statnews.com Richard Lynn's work has been repeatedly condemned for using flawed methodology and deceptively collated data to support racism. It's past time to retract the studies.

How you model phenotypes really matters: "When associations between items and PGSs were not adjusted for all associations between network nodes ... PGSs were associated with a broader set of items than those identified by network analysis." jamanetwork.com/journals/jam...

Polygenic Scores and Networks of Psychopathology Symptomsjamanetwork.com This cross-sectional study evaluates associations between polygenic scores with psychiatric disorder symptoms and relevant comorbid phenotypes.

Estimated SNP heritability versus kinship heritability from the very interesting and absolutely massive recent registry study of Meijsen et al.[ www.nature.com/articles/s41... ]. Both estimates include shared environment in their own ways.

Heritability estimates under the "Limiting Pathways" model [Zuk et al 2012; pubmed.ncbi.nlm.nih.gov/22223662/]

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Sasha Gusev

#stats people, I have a YouTube account! I will be making quick YouTube videos on topics related to statistics, meta-analysis, and psychometrics. Check it out: youtube.com/@matthewbjan...

Matthew B. Janéyoutube.com

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Sasha Gusev

Seeing data as t-SNE and UMAP do www.nature.com/articles/s41... #bioinformatics #genomics #visualization #tsne #umap

Seeing data as t-SNE and UMAP do - Nature Methodswww.nature.com Dimension reduction helps to visualize high-dimensional datasets. These tools should be used thoughtfully and with tuned parameters. Sometimes, these methods take a second thought.

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Sasha Gusev

Just noticed that the table of contents of my upcoming (October) book, Understanding the Nature Nurture Debate is posted on the Contents tab here: www.cambridge.org/gb/universit...

I've written the first part of a chapter on the heritability of IQ scores. Focusing on what IQ is attempting to measure: gusevlab.org/projects/hsq... A summary thread of the key points here: threadreaderapp.com/thread/17894...

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Sasha Gusev

Here's a pretty good summary of the state of the field for how genetic data can be applied in economics research. On top of tying much of the field together in a consistent framework, there are also a handful of novel theoretical results. Excited to see this out! t.co/d7g1SEEB6C

Social-Science Genomics: Progress, Challenges, and Future Directionst.co Founded in 1920, the NBER is a private, non-profit, non-partisan organization dedicated to conducting economic research and to disseminating research findings among academics, public policy makers, an...

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We’re recruiting for multiple positions in my lab in New York and Stockholm, at MSc and PhD levels. If you’re interested in pursuing creative systems genetics questions with tools/data like Developmental GTEx, CRISPR and single-cell, please read further / share. 1/

Very intriguing paper showing *within-family* genetic principal components have (weak but significant) direct effects on height and education. PC4 in the White British population is at the level of very recent structure within Wales? And PC21?! www.biorxiv.org/content/10.1...

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Sasha Gusev

In this new pre-print we tried to understand why autoimmune disease and type 1 diabetes co-occur in families using nationwide registries and genetic data. www.medrxiv.org/content/10.1...

Interesting study looking at how common education polygenic scores modify the effect of rare developmental delay genes. Given that the EA PGS is actually 2/3rds dynastic environment (or stratification), this suggests that environment could be a substantial compensatory force.

Genetic modifiers of rare variants in monogenic developmental disorder loci - Nature Geneticswww.nature.com Analysis of genetic modifiers of 599 developmental disorder genes in the UK Biobank found that rare variant burden within this set, as well as the common polygenic background, can alter the expressivi...

Knyspel + Plomin 2024 [ www.sciencedirect.com/science/arti... ] compared factor and network models of cognitive abilities in twins. The two models produce (significant) opposite estimates of the relationship between factor loading and additive genetic variance. 🤷

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Congratulations to Carl Veller on the publication of his article on confounding in population and family GWAS journals.plos.org/plosbiology/...

Interpreting population- and family-based genome-wide association studies in the presence of confoundingjournals.plos.org GWASs aim to estimate direct effects of genotype on an individual’s phenotype, but this can be subject to genetic and environmental confounds and

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Sasha Gusev

I kicked off a series of posts on the "end of GWAS" . It'll be 5 posts, an intro and posts on GWAS of Height, depression, education and schizophrenia, each ample size > 500.000 individuals. I wrote these between jobs to think about whats next for my field & me nivard.substack.com/p/gwas-endga...

GWAS: endgame Vol. 1nivard.substack.com What will the first of the last GWAS look like, whats after GWAS?

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Another blog post. (On the last month of a leave, in case you are wondering.) "From Spelling Test to IQ to g." ericturkheimer.substack.com/p/from-spell...

From Spelling Test to IQ to gericturkheimer.substack.com Ability without essentialism

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Sasha Gusev

In a new preprint w collaborators Jiaxin Hu and Miaoyan Wang at Univ Wisconsin www.biorxiv.org/content/10.1... we develop a method to map QTL that change gene coexpression networks. For each genetic marker in an F2 cross, split the data by genotype & build a coexpression network for each genotype

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New paper out with Sarah Greer Rodock: "Spit For Science and The Limits of Applied Psychiatric Genetics" I think it is open access, though I had a hard time getting to it. muse.jhu.edu/pub/1/articl...

Project MUSE - Spit for Science and the Limits of Applied Psychiatric Geneticsmuse.jhu.edu

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Sasha Gusev

Thrilled to see our work on genetic prediction of immune checkpoint inhibitor-mediated colitis published t.co/nsCV47ahwl

Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis - Nature Communicationst.co Colitis is one of the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors. Here the authors show that a polygenic risk score for ulcerative coli...

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Sasha Gusev

We know the importance of subtle gene dosage variation; yet much of molbio is based on gene KO/KD. In our new preprint, our (ex-) postdoc Julia Domingo introduced subtle modulations of transcription factor dosage by CRISPRi/a, and quantified responses by scRNA-seq. 1/ www.biorxiv.org/content/10.1...

Non-linear transcriptional responses to gradual modulation of transcription factor dosaget.co bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

Some thoughts on the ability to distinguish populations with genetic variation, why that means little for trait differences, and why there are other good reasons to collect diverse data: threadreaderapp.com/thread/17633...

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Sasha Gusev

Excited to share our review paper in Cell! With @sashagusevposts.bsky.social @sramach.bsky.social and Yang Li we discuss the genetic and molecular architecture of human traits, future opportunities, challenges and ways forward. authors.elsevier.com/a/1igrbL7PXq...

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Sasha Gusev

I have been following the discussion around how best to represent and label human genetic variation, and thought it might also be worth discussing an aspect of the broader context. 1/n

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Sasha Gusev

Personal news 🚨: ill be joining the University of Bristol as a professor of Genetic Epidemiology April 1st! There will be a longer thread on how I got here, I am forever grateful for many people at the VU and elsewhere who got me here! UK scientists pls reach out and let’s catch up & collaborate!

Some writing about race, genetic ancestry, analyses of large biobanks, and human history here: gusevlab.org/projects/hsq... Which I've also summarized in this thread: threadreaderapp.com/thread/17603... This is meant to be a critical review and I'm always happy to hear similarly critical feedback.