Hakhamanesh Mostafavi
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hakha.bsky.social
Hakhamanesh Mostafavi
@hakha.bsky.social
Assistant Professor at NYU Langone. Genetics, evolution and biology of complex traits and diseases.
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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!
Reposted by Hakhamanesh Mostafavi
Registration for the 2026 NY Area Population Genetics meeting is now open, at events.simonsfoundation.org/e0mEoL?rt=8k.... Registration is free but required; if you are submitting an abstract, note that the deadline is *January 30th*.
January 14, 2026 at 9:37 PM
Reposted by Hakhamanesh Mostafavi
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.
January 5, 2026 at 7:27 PM
Reposted by Hakhamanesh Mostafavi
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
Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits
Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, ...
tinyurl.com
January 5, 2026 at 6:42 PM
Reposted by Hakhamanesh Mostafavi
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
High false sign rates in transcriptome-wide association studies
Transcriptome-wide association studies (TWAS) are widely used to identify genes involved in complex traits and to infer the direction of gene effects on traits. However, despite their popularity, it r...
doi.org
January 6, 2026 at 2:48 AM
Reposted by Hakhamanesh Mostafavi
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
High false sign rates in transcriptome-wide association studies
Transcriptome-wide association studies (TWAS) are widely used to identify genes involved in complex traits and to infer the direction of gene effects on traits. However, despite their popularity, it r...
doi.org
January 6, 2026 at 2:30 AM
Reposted by Hakhamanesh Mostafavi
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...
December 21, 2025 at 6:07 AM
Reposted by Hakhamanesh Mostafavi
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.
Looking for a postdoc opportunity in computational & engineering applications in medicine & health care? Apply to the Malone Fellows Program and work with mentors in genomics, AI/data science, robotics, human-computer interaction, augmented/virtual reality, & more.

Deadline coming up: Jan 31, 2025
Malone Fellows Program
malonecenter.jhu.edu
December 16, 2025 at 7:29 PM
Reposted by Hakhamanesh Mostafavi
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🧵:
Causal modelling of gene effects from regulators to programs to traits - Nature
Approaches combining genetic association and Perturb-seq data that link genetic variants to functional programs to traits are described.
www.nature.com
December 11, 2025 at 5:54 PM
Reposted by Hakhamanesh Mostafavi
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)
December 11, 2025 at 3:15 AM
Reposted by Hakhamanesh Mostafavi
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!
December 11, 2025 at 3:04 AM
Reposted by Hakhamanesh Mostafavi
As promised, a longer thread on what I consider to be some of the most interesting and important contributions of this paper (1/10)
Here, we show that the genetic relatedness matrix (GRM) can be used to control this type of genetic confounding. (Though our model has not been explicitly described in prior literature, we show that it is the basis for existing methods to control genetic confounding... but more on that later.) (4/6)
December 1, 2025 at 9:20 PM
Reposted by Hakhamanesh Mostafavi
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!
December 2, 2025 at 12:11 AM
Reposted by Hakhamanesh Mostafavi
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...
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
Reposted by Hakhamanesh Mostafavi
#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)
November 24, 2025 at 11:26 AM
Reposted by Hakhamanesh Mostafavi
@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...
How do genetic association studies rank genes?
Genome-wide association studies and rare-variant burden tests reveal complementary aspects of trait biology.
www.nature.com
November 19, 2025 at 6:43 PM
Reposted by Hakhamanesh Mostafavi
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.
November 14, 2025 at 5:05 PM
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
Apply - Interfolio {{$ctrl.$state.data.pageTitle}} - Apply - Interfolio
apply.interfolio.com
November 14, 2025 at 3:51 PM
Reposted by Hakhamanesh Mostafavi
An empirical approach to evaluating the prevalence of long-lived balancing selection in humans--and important limitations. Work by @hannahmm.bsky.social
November 11, 2025 at 7:14 PM
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.
How do GWAS and rare variant burden tests rank gene signals?

In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!

🧬🧪🧵

www.nature.com/articles/s41...
Specificity, length and luck drive gene rankings in association studies - Nature
Genetic association tests prioritize candidate genes based on different criteria.
www.nature.com
November 7, 2025 at 6:33 PM
Reposted by Hakhamanesh Mostafavi
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 do GWAS and rare variant burden tests rank gene signals?

In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!

🧬🧪🧵

www.nature.com/articles/s41...
Specificity, length and luck drive gene rankings in association studies - Nature
Genetic association tests prioritize candidate genes based on different criteria.
www.nature.com
November 7, 2025 at 4:08 AM
Reposted by 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
Ancient origin of an urban underground mosquito
Understanding how life is adapting to urban environments represents an important challenge in evolutionary biology. In this work, we investigate a widely cited example of urban adaptation, Culex pipie...
www.science.org
October 25, 2025 at 4:46 AM
Reposted by Hakhamanesh Mostafavi
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/...
Simple scaling laws control the genetic architectures of human complex traits
Genome-wide association studies have revealed that the genetic architectures of complex traits vary widely. This study shows that differences in architectures of highly polygenic traits arise mainly f...
journals.plos.org
October 24, 2025 at 1:51 AM
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.
October 13, 2025 at 11:19 PM
Reposted by Hakhamanesh Mostafavi
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.
August 6, 2025 at 5:18 PM
Reposted by Hakhamanesh Mostafavi
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.
Home - ProbGen 2026
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probgen2026.github.io
June 6, 2025 at 5:52 PM