Our paper about how ancestral recombination graphs can be used to detect "phantom" genetic interaction signals (that arise due to the genealogy, rather than "real" epistasis) is out in Genetics! Nice thread here by @linoafferreira.bsky.social

academic.oup.com/genetics/adv...

Thank you!

We hope this approach will enable others to search for (and perhaps find!) epistatic effects in cis, and through this to learn more about the genetic basis of complex phenotypes.

Thanks for reading! (end 🧵)

In contrast, our method only requires publicly available WGS data for samples of similar ancestral background (we use 1KGP) whose information is efficiently encoded in the form of an ARG. This makes it applicable in settings where WGS data is not available (including for non-human species).

it was very difficult to rigorously test for such effects.

WGS data or dense imputation panels allowed for checking whether any neighbouring variant accounted for a putative interaction but only if this data was available for the same sample in which the epistasis testing was done.

evidence *against* the existence of a problematic variant.

This allows us to quantify the observed evidence either for or against a potential interaction being real.

Epistasis between variants in cis could be common (or at least less rare than that between variants farther apart) but until now...

the genealogy (in the form of an ARG).

We first derive the conditions that a problematic variant would have to satisfy to yield a significant interaction in the first place. We then look for clades within the ARG that might harbour such a variant or, conversely, for clades that provide...

But (by definition) we don't observe the possible hidden variants that might be driving the putative interaction. So how can we test for the existence of a variant that we don't see?

In the paper, we derive tests for whether phantom epistasis is likely to arise between two variants due to...

effect of a third, unobserved variant. This has been called "phantom epistasis" and, far from being a theoretical issue, has led to the retraction of a high-profile paper.
www.nature.com/articles/s41...

Given a potential interaction, we would like to know if it might be a "phantom" effect...

Genetic interactions are hard to find, and very few have been identified for humans. One challenge to their detection is that we can't reliably test for interactions between neighbouring variants: if we see that two variants in LD interact, their interaction may actually be tagging the *additive*...

Epistasis happens when two genetic variants have a combined effect on a phenotype that is different (greater or lesser) than the sum of their effects when present in isolation: the whole is more (or less) than the sum of its parts. See this great thread for an overview:
bsky.app/profile/sash...

Delighted to see this paper with @anaignatieva.bsky.social now published in Genetics!
academic.oup.com/genetics/adv...

We tackle a thorny issue arising in statistical tests for genetic interactions (epistasis) using ancestral recombination graphs (ARGs)... 🧵

Excited to have this out there! Comments are very welcome.

📣 Two ERC-funded positions are available in the lab! If you are interested in exploring the mechanisms underlying mutation, we’d love to hear from you.

PhD: shorturl.at/Oc04N
Postdoc: shorturl.at/1ShHB

RPs and shares would be greatly appreciated!
🧪🧬🖥️ #ScienceJobs #PostdocJobs

The Hinch lab is looking for an enthusiastic statistician, mathematician or physicist to join us as a post doc!

If you'd like to use big data to decode the inner workings of our cells, apply now: germlinegenomics.web.ox.ac.uk

Please re-post and thanks!
#PhDjobs #Postdocs #STEM #meiosis #genomics

Congratulations to Carl Veller on the publication of his article on confounding in population and family GWAS
journals.plos.org/plosbiology/...

Beautiful figures and slides!

a generous stipend (+ a 50k research grant!) and choose their own supervisor from among a long list of amazing researchers, and all this in Oxford.

If you know of anyone interested in doing a PhD in genetics, encourage them to apply!

My PhD programme, the 'DPhil in Genomic Medicine and Statistics' at the Wellcome Centre for Human Genetics in Oxford, is accepting applications for next year!

I'm coming to the end of my studies after four years and feel so fortunate to have been part of it. Students get...

First post on this celestial platform to mark a happy occasion: I've submitted my PhD thesis!

I've celebrated and rested well and am now back to working on research after all the writing... Excited for what's to come!