In a prospective validation of a genetically supported target, asundexian, a factor XIa inhibitor is now moving toward approval for secondary stroke prevention following the positive phase 3 OCEANIC-STROKE trial. open.substack.com/pub/thecodon...

Factor XI inhibition: from human genetic signal to the clinic

Asundexian moving toward approval for secondary stroke prevention

open.substack.com

There’s an increasingly popular social media debate about whether LDL is the main driver of atherosclerosis. Beyond numerous trials, human genetic data represent a key evidence pillar that links LDL with atherosclerosis. I wrote a long piece on the topic open.substack.com/pub/thecodon...

The cholesterol debate through the lens of human genetics

How strong is the genetic evidence supporting LDL as the causal driver of cardiovascular disease?

open.substack.com

Thrilled to see this out. What started out as a chat several years back with @drfejzo.bsky.social about leveraging publicly available data on hyperemesis gravidarum GWAS turned into a wonderful collaboration with April Shu, @mvaudel.bsky.social, @xwww.bsky.social and many others! rdcu.be/fdl9k

Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting

Nature Genetics - Multi-ancestry GWAS meta-analysis identifies risk loci for severe nausea and vomiting of pregnancy. Downstream analyses explore maternal and fetal contributions of these loci and...

rdcu.be

Our new paper at JACC: Heart Failure (@jaccjournals.bsky.social) provides human genetic support for a link between IL-6 inhibition and lower risk of heart failure. www.sciencedirect.com/science/arti...

In our new preprint, we develop a genetic proxy for hepatic AGT synthesis inhibition, enabling human genetic validation of a promising emerging antihypertensive target. AGT is an emerging target of liver-delivered RNA-based antihypertensive therapeutics👇

You might have heard the claim that human genetic evidence increases drug success rate by 2-3 times. I did a deep dive into the paper making the claim, discussing the nuances of using human genetic insights in drug development.

#ESSW2025 session report: Session II brought together Dr. Shoamanesh, Dr. Strbian, Marios Georgakis & Dr. Gauberti to explore how stronger methodology can move #StrokeResearch closer to clinical practice. 🔗Read the #ESOBlog: https://ow.ly/kF9U50XHkGh #Stroke #Neurology

In our new preprint, we present the largest genomic exploration of arterial aging to date, leveraging photoplethysmography (PPG)–derived pulse waveforms from 115,000 UK Biobank participants. Our results provide insights into potential strategies to mitigate arterial aging👇

@mariosgeorgakis.bsky.social , not recently active on #Bluesky, on the methods for prioritizing drug targets for complex diseases using human genomic data

If you're up for a niche read on challenges in translating anti-inflammatory therapies for atherosclerotic stroke prevention, have a look at our review in Neurology

A great read👇 Some social science genetics papers are among the most interesting and methodologically rigorous I've read. From biology to mating choices and inequalities, they deal with very fundamental concepts of what makes as humans.

Abdel Abdellaoui@dr-appie.bsky.social · 11mo ago

Some people call it a minefield. Others call it dangerous, even irresponsible. I call it the most promising field in life sciences. My love letter to social science genetics: communities.springernature.com/posts/a-love...

Extremely proud to see this work led by @mihkeljesse.bsky.social now out on biorxiv!

@mihkeljesse.bsky.social · 12mo ago

After 1.5 years of work in @kauralasoo.bsky.social’s lab, we finally published my preprint! We introduce gpu-coloc, a GPU-accelerated implementation of coloc, show comparability to CLPP and aim to provide practical guidelines. Now accessible on BioRxiv: www.biorxiv.org/content/10.1...

I'm often asked how human genetic data can be used to validate drug targets. In our new ‪@natcardiovascres.nature.com‬ paper, we provide an end-to-end framework for genetically validating IL-6 inhibition for atherosclerotic cardiovascular disease outcomes 🧵

IL-6 inhibition lower risks of cardiovascular disease with no increase in infection, supporting pharmacological treatments of IL-6 rather than its receptor @natcardiovascres.nature.com @mariosgeorgakis.bsky.social www.nature.com/articles/s44... www.nature.com/articles/s44...

Amid the hype of using polygenic scores for embryo selection, some thoughts on their implementation potential in real-world settings (and problems) 👇

The modern cardiovascular drug development landscape has been largely shaped by human genetic studies. Emerging IL-6 therapeutics are a landmark example. In this paper with the Tourmaline Bio team, we review how genetics pinpointed IL-6 signaling as a causal driver of athero-inflammation👇

We recently published a preprint with the protocol & pilot data from 𝐀𝐭𝐡𝐞𝐫𝐎𝐌𝐈𝐂𝐒. AtherOMICS is a biobanking project built in our lab over the past 3 years aiming to provide access to multi-omics/multi-modal data from human atherosclerotic tissue❗ Some innovations of AtherOMICS👇

🚨ICYMI 🫀🧬 from @mariosgeorgakis.bsky.social & co 📄Single-cell transcriptome-wide Mendelian randomization and colocalization analyses uncover cell-specific mechanisms in atherosclerotic cardiovascular disease

Single-cell transcriptome-wide Mendelian randomization and colocalization analyses uncover cell-specific mechanisms in atherosclerotic cardiovascular disease

We present a stringent single-cell analytical framework using transcriptome-wide Mendelian randomization and colocalization. By resolving cell-type-specific expression effects missed by bulk methods, ...

cell.com

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Yet, we lack circulating biomarkers for systemic atherosclerosis burden. Check out our new preprint describing the development of proteomic signatures of atherosclerosis👇

Facial characterisics are to a very large extent genetically determined🧬🤓 Now, it seems we could use genetic variation to predict 3D face structures with key implications for both forensic science and ethics👇

I read the latest GWAS on long COVID. Is it just me, or is it odd that the main analysis used population controls (broad definition) instead of individuals with SARS-CoV-2 infection without long COVID (strict definition)?

A new IL-6–targeting agent enters the inflammation space in cardiovascular disease❗️ Pacibekitug (Tourmaline Bio), an s.c. anti-IL6 mAb showed hsCRP reductions in patients with stage 3/4 CKD and hsCRP>2 mg/dl in phase 2. Big advantage the potential for quarterly dosing💉

Interesting paper on sex differences in the genetic regulation of the plasma proteome in Fenland (N=8348, SomaLogic) and UKB (N=48,017, Olink)👇

Great review of the evolving landscape of therapeutics targeting triglycerides & remnant cholesterol. Human genetics has been key to shaping this field with discoveries of loss-of-function variants in APOC3, ANGPTL3, ANGPTL4 having directly triggered clinical development 🧬-->💊

A great week for genetics, omics, and precision medicine — many exciting reads 🧬 1⃣ Circadian gene expression regulation by rhythmic genetic variants 🧵[1/8]

Profiling the proteome has turned out to be a challenging task. Available platforms offer increasingly broader coverage, but often yield different results for the same proteins. This preprint compares quantifications of mass spectrometry & Olink in the same samples👇

Most disease-associated GWAS signals fall in the non-coding genome🧬 Although assumed to influence expression, pinpointing the causal gene isn't easy. Two ways include: 1⃣eQTL mapping in relevant tissues/cells 2⃣in vitro CRISPRi screens This preprint compares the two👇

Exciting reads on genetics, omics, & precision medicine this week 🧬 1⃣ Tissue-specific atlas of protein co-abundance [1/6] 🧵

Two presentations from our lab this week🚨 👉Lanyue Zhang, awarded a Young Investigator Fellowship, on proteomic signatures of atherosclerosis at the EAS Congress in Glasgow 👉Anushree Ray, recipient of a Travel Award, on single-cell drivers of atherosclerosis at the CHARGE meeting in Maryland

Two meta-analyses in Eur Heart J, pool the available trial data on the use of colchicine for secondary prevention of cardiovascular events. Slight differences in inclusion criteria (e.g. long-term vs. any use), but both generally point to a benefit.