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Adriaan

@adriaan-vd-graaf.bsky.social

270 followers 170 following 21 posts

Post-doc in statistical genetics at the University of Lausanne. Working on developing new techniques for observational causality and validation datasets on which to test our inferences

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Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

Our paper, MR-link-2 has just been published! Offering pleiotropy robust Mendelian randomization from a single region! www.nature.com/articles/s41...

A network of metabolites and their potential causal relationships. Green edges are Detected by the statistical causal inference method MR-link-2

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Reposted by Adriaan

Chris Wallace @chr1sw.bsky.social · Aug 4

Tip for presentations: avoid saying "I don't think this audience needs an introduction to X". Try instead giving a v brief introduction tailored to the key points you will reference in the rest of the talk.

So often people assume I have knowledge I don't, and this hurts my ability to follow.

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Adriaan @adriaan-vd-graaf.bsky.social · Aug 18

Using google gemini with grounding for later reference? Make sure you download your links before they expire... :(

Reposted by Adriaan

Robin Hofmeister @rjhfmstr.bsky.social · Aug 6

🚨 Our parent-of-origin study is out in Nature! 🧬
Maternal and paternal alleles can have distinct — even opposite — effects on human traits, revealing a hidden layer of genetic architecture that standard GWAS miss.
🔗 www.nature.com/articles/s41...

Highlights below!

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Adriaan @adriaan-vd-graaf.bsky.social · Aug 6

Wild ride.

Health Nerd @gidmk.bsky.social · Aug 5

Someone just sent me this study, and all I can say is that I don't understand why anyone would bother investigating this question. 1/n

Reposted by Adriaan

katja heuer @k4tj4.bsky.social · Jul 27

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To predict the behaviour of a primate, would you rather base your guess on a closely related species or one with a similar brain shape? We looked at brains & behaviours of 70 species, you’ll be surprised!

🧵Thread on our new preprint with @r3rt0.bsky.social , doi.org/10.1101/2025...

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Adriaan @adriaan-vd-graaf.bsky.social · Jul 21

Sure! It’s mostly my own incompetence holding me back! But will do when I encounter a bug or really don’t know what to do!

Adriaan @adriaan-vd-graaf.bsky.social · Jul 21

Congratulations! I’ve been using the code already for some projects! Happy to see it being published!

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Reposted by Adriaan

Nicholas Mancuso @nmancuso.bsky.social · Jul 21

Super excited to see this out. What started as some math in a grant in 2020, to a student deciding to take this on in 2022, to published in 2025.

These things can take time and patience is key!

Nature Genetics @natgenet.nature.com · Jul 21

📢OUT TODAY @natgenet.nature.com

📰Improved multiancestry fine-mapping identifies cis-regulatory variants underlying molecular traits and disease risk.

By @zeyunlu.bsky.social, @nmancuso.bsky.social and colleagues.

⬇️

www.nature.com/articles/s41...

Improved multiancestry fine-mapping identifies cis-regulatory variants underlying molecular traits and disease risk - Nature Genetics

SuShiE is a multiancestry fine-mapping method for molecular quantitative trait loci that leverages linkage disequilibrium heterogeneity to improve resolution, infer cross-ancestry effect size correlat...

www.nature.com

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Reposted by Adriaan

Sasha Gusev @sashagusevposts.bsky.social · Jul 12

I wrote a little bit about a cool recent paper looking at heritability estimates from very large registry data, and how we still really don't understand why outcomes track in families. A short 🧵:

We still do not understand family resemblance

...

theinfinitesimal.substack.com

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Reposted by Adriaan

Tabea Schoeler @tabeasch.bsky.social · Jul 8

🚨New preprint is out!

How do genetic effects on complex traits change with age? In this work, we compare different approaches to obtain age-varying genetic effects, and show how design and modeling choices can impact the conclusions we draw.
shorturl.at/17snd
A thread 🧵👇

Design and model choices shape inference of age-varying genetic effects on complex traits

Understanding how genetic influences on complex traits change with age is a fundamental question in genetic epidemiology. Both cross-sectional (between-subject) and longitudinal (within-subject) appro...

shorturl.at

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Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

This work wouldn't have been possible without @zkutalik.bsky.social nor Chiara Auwerx, Carolina Borges, Robert Warmerdam, Lude Franke, Urmo Võsa and the eQTLGen consortium!

Thanks for reading all the way, and if you have ANY questions, happy to interact!

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

So that's MR-link-2 in a nutshell!

There's a lot more little gems in the paper, so do have a read! www.nature.com/articles/s41...

Interested in running MR-link-2? take a look at the GitHub!
github.com/adriaan-vd-g...

All feedback is welcome! Happy to guide even total beginners!

MR-link-2: pleiotropy robust cis Mendelian randomization validated in three independent reference datasets of causality - Nature Communications

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical sc...

www.nature.com

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

And as a final ground truth we use the markergenes that are used to identify cell types in single cell experiments to the cell type proportions themselves.

Here, the cell type should influence gene expression, and not the other way around! MR-link-2 has very good discriminative ability.

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Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

We think MR-link-2 truly estimates pleiotropy!

When we correlate the MR-link-2 estimate of pleiotropy with the deviation (individual Q statistic contribution of each region) from meta-analysis, we find highly significant correlation

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

When we look at biomarker -- disease causality, we find that MR-link-2 identifies all of the true positives we tested.
All while having a median per locus false positive rate of 0.09 in the true negatives (compared to 0.15 of other methods): MR-link-2 has lower false positive rates

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

Our ground truth is set up to be quite stringent, but when we look at other significant results outside of the ground truth, MR-link-2 is the only method that finds the causal relationship between pyruvate and citrate, a key citric acid cycle link. As well as other very compelling examples.

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

And MR-link-2 is very competitive in discriminating between direct reactions and reactions that are super far away (Negative distance).

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

Here, we find that MR-link-2 is better at identifying the correct causal effect estimate between substrates and products (should be positive) than other MR-methods

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Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

Metabolic pathways

We used 4 metabolite QTL studies, and 3 metabolic pathway references to build a network of reactions that an MR method is supposed to detect.

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

Now, you may be wondering, sounds like something cool, but how ever would you prove that it works?

We spent a lot of time on to build ground truth in human causality. We compiled ground truth causality from metabolic pathways, biomarker-disease pairs and cell types and marker genes.

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

The trick is that we use all the SNPs in an associated region, compared to other methods that usually only use one SNP.

Diagrams of conventional Mendelian randomization, compared to the MR-link-2 method. The MR-link-2 method uses correlated SNPs in an associated region to estimate a causal effect, and pleiotropy.

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

We developed MR-link-2, an MR method robust to pleiotropy. The unique bit is that it only requires a single associated region for it to work. Interested?

Have a look at the code and examples on the github!
github.com/adriaan-vd-g...

Adriaan @adriaan-vd-graaf.bsky.social · Jul 4

Our paper, MR-link-2 has just been published! Offering pleiotropy robust Mendelian randomization from a single region! www.nature.com/articles/s41...

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Reposted by Adriaan

Tabea Schoeler @tabeasch.bsky.social · May 19

Happy to share our new study on genetic & environmental contributors to age-related decline in ~100K UK Biobank participants!

Here, we used simulation work + longitudinal GWAS and downstream analyses to explore risks involved in cognitive/physical decline
(1/)🧵🧵

shorturl.at/99gqL

Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline - Nature Communications

Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Bioban...

shorturl.at

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Reposted by Adriaan

Dr. Lucky Tran @luckytran.com · Apr 28

Deaths from heart disease down 75%, that’s NIH.

Deaths from stroke down 75%, that’s NIH.

HIV/AIDS no longer a death sentence, that’s NIH.

99% of FDA approved drugs in the last decade, that’s NIH.

Please show this video to anyone who doesn’t understand why the NIH is so important.

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