Really excited to share our metabolite ratio QTL work Friday!

- 25% more findings from already existing QTL studies

- We proxy enzymatic activity that is otherwise unmeasured

- We implicate ABCG2 as a PFOS 'forever chemical' transporter

Come by the poster and say hi!

Hi #ASHG2025, the Lausanne team made it to Boston ! Excited to present our latest discoveries — come say hi and learn more about our research! @samuelmoix.bsky.social @rjhfmstr.bsky.social

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

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.

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

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

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

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

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.

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.

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

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