Pretty wild: www.science.org/content/arti...

Genetics reveal why people respond differently to GLP-1 weight-loss drugs Genetic variants in GLP1R and GIPR, which encode targets of GLP-1-based medications, offer insights into why responses to these drugs vary and who might face adverse effects.

Why do people respond differently to GLP-1 weight-loss drugs? Genetics has the answer - provided in this genome wide association study led by @adamauton.bsky.social www.nature.com/articles/s41...
🧪

www.nature.com/articles/d41...

it's a fair question in principle, but the biology of the hits (drug target genes, drug-specific effects) provides strong evidence these are genuine pharmacogenetic associations rather than confounded background effects.

Apologies Shai - what was cited out of context? 🙏

Genetic predictors of GLP1 receptor agonist weight loss and side effects - Nature Identification of genetic variants associated with the efficacy and side effects of GLP1 medications could underpin development of precision medicine approaches in the treatment of obesity.

Were you inspired by our paper on the genetics of GLP-1 drug response? www.nature.com/articles/s41...

Want to make impactful discoveries with the world's best genetic dataset? We're hiring!

StatGen: tinyurl.com/ys4mvhej
Risk Prediction: tinyurl.com/psamt294
Data Products: tinyurl.com/2ff7eavb

Unlocking the Genetics of GLP-1 Medications Through Crowdsourced Science at 23andMe By pairing a rapid "research flywheel" with large-scale genomic data, 23andMe Research Institute scientists identified GLP1R and GIPR variants associated with some of the variability in individual res...

A nice “behind the paper” explainer here: communities.springernature.com/posts/unlock...

Huge congratulations to the incredible 23andMe Research Team for getting this over the finish line. And as always, a huge thank you to the 23andMe participants who made all this research possible!

Check out the full paper here: www.nature.com/articles/s41...

Why does this matter? As these medications become increasingly widely prescribed, precision medicine could help clinicians tailor the choice of drug and adjust the speed of dose escalation to maximize efficacy and minimize side effects.

Of course, genetics isn't the whole story. To build a predictive model of GLP-1 medication efficacy, we combined clinical and demographic factors with the genetics we had identified. These models do a reasonable job at predicting efficacy:

This time we found variants in both GLP1R and GIPR associated with nausea and vomiting. Interestingly, the GIPR association was specific to patients taking tirzepatide (aka Mounjaro or Zepbound)... this also makes sense; tirzepatide targets both GLP1R and GIPR!

The variant is relatively common (~10-40%). On average, carriers of this variant see an extra 0.76 kg of weight loss per copy of the effect allele. But it’s not just about weight loss; we also investigated GLP-1 medication side effects.

By running a GWAS on data we collected from an online survey about GLP-1 medication, we found a missense variant in GLP1R that predicts treatment success. This makes sense! GLP1R is the target of the GLP-1 medications!

GLP-1 receptor agonists have transformed the management of obesity. But patient experiences vary wildly - some see massive weight loss, others see little. Some people feel ill taking these medications, others do not. How much of this is driven by DNA?

Delighted to share our latest research from the 23andMe Research Team, just published in @nature.com !
We looked at data from >27,000 participants to uncover how human genetics influences weight loss efficacy and side effects of GLP-1 medications like semaglutide. A short thread 🧵👇

Picture of Earth in space, courtesy of NASA

Artemis looks back at the home planet. www.nasa.gov/image-articl...

New opportunity at 23andMe Research Institute! We're looking for a new team member to help us build and deliver clinically useful risk prediction models that can be deployed to consumers and clinicians. 23andme.wd5.myworkdayjobs.com/en-US/23/det...

Really awesome stuff.

This paper is bananas. I love everything about this. Such a fantastically smart design, signals popping out like nobody's business.

www.biorxiv.org/content/10.1...

Who is at #AGBTGM26 ?

Science Bluesky is now much better than Science Twitter is… but I still miss peak pre-pandemic Science Twitter.

Davis Summer Population Genomics Program Want to learn population genetics? Please fill out this form to indicate your potential interest in a 2-week intensive online summer population genetics course taught by Jeffrey Ross-Ibarra and Graham...

Fun news! @gcbias.bsky.social and I are teaching a 2-week online population genetics workshop this summer to raise money for the Center for Population Biology at UC Davis. We're trying to gauge interest -- please fill this out if you might be interested! And please share broadly!

I mean, death from infectious disease clearly has a genetic component related to the immune system… the distinction between intrinsic and extrinsic seems a little slippery.

Clever evolutionary geneticists are liking my post, so I guess I might be on to something…

Heritability of intrinsic human life span is about 50% when confounding factors are addressed How heritable is human life span? If genetic heritability is high, longevity genes can reveal aging mechanisms and inform medicine and public health. However, current estimates of heritability are low...

I haven't thought deeply about this, but ... if heritability is the proportion of the variance attributable to genetics, and I remove some variance attributable to "the environment", then should I be surprised that the heritability goes up? @sashagusevposts.bsky.social help!?
doi.org/10.1126/scie...

We're hiring! We're seeking a talented statistical geneticist to join the team. Come work with the greatest genetic dataset in the world, and help shape the 23andMe Research Institute in our nonprofit era!

23andme.wd5.myworkdayjobs.com/en-US/23/det...

Brenna Henn Wanted to Improve Genetic Medicine. Then Her N.I.H. Grant Was Cut. Brenna Henn had a long-term grant to study the genetic diversity of Africans and people of African descent. Then her N.I.H. funding was cut.

Brenna Henn Wanted to Improve Genetic Medicine. Then Her N.I.H. Grant Was Cut.

I've been thinking about the "virtual cell" concept and wanted to write up a few thoughts. Specifically on how I think the prior experience in GWAS informs the most likely way these models will be useful.

andrewcarroll.github.io/2025/12/23/t...

Completely agree. I was lucky to get to work with Richard on the 1000 Genomes. He was always so generous with ideas and insights.

Congratulations to Richard Durbin on being awarded our Genetics Society Medal!

Electric vehicle owners to face pay-per-mile tax Drivers of electric cars will pay a road charge of 3p per mile, while plug-in hybrid drivers will pay 1.5p per mile from April 2028.

Keeping fuel duty at the same level for 15 years, while phasing in a cumbersome-to-implement tax on EV owners seems insane.

www.bbc.com/news/article...