Gregor Gorjanc

An interesting rabbit hole that I have yet dug into is that population structure alone cannot drive genetic variance inflation in the estimates. We did a spatial simulation exhibiting a very strong isolation-by-distance pattern. The estimated variance components are consistent.

Very very happy that this work is out. Led by the brilliant @epigenci.bsky.social and other fab collaborators! I have been thinking about this for years, but couldn’t do it without the team;) Enjoy the reading!

Darn, too much to read;)

Am I the only person to read teaspoon as teasposons 😂😂

In deeper pedigrees, the estimand pertains to the founders of the population. In SNP LMMs, do you know who these are?

Genetic variance of a population is a random variable and not a parameter. It becomes one only if you condition on a particular population in space and time. Given this choice, the variance of other populations is still left as a random variable.

How do genetic association studies rank genes? Genome-wide association studies and rare-variant burden tests reveal complementary aspects of trait biology.

@hakha.bsky.social and I wrote a Research Briefing (with a lay summary + "behind the scenes") of our paper on how genes are prioritized by GWAS and rare variant burden tests. 🧬🧪

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

Wonderful story from a young scientist about his experience with @official-smbe.bsky.social and competing in GHIST. I'm so glad to see the next generation thriving.

Jaison is an author on the GHIST paper, and the 2025 competition ends in 14 days. Now's your chance to dive in and join! ghist.bio

Haseman-Elston regression is bit of an irony for massive biobanks because it throws away the statistical precision that was gained by accounting for more samples. You might be able to analyze more data, but you don't get more information out of it.

Lots in Evolution and similar journals, no?

I still give this advice routinely for students looking for career advice. Write and learn in public.

One thing I missed in this post is CONSISTENCY.

As with athletic pursuits, people overestimate what you can accomplish in a week and underestimate what you can do in a year. Writing is the same.

Specificity, length and luck drive gene rankings in association studies - Nature Genetic association tests prioritize candidate genes based on different criteria.

How do GWAS and rare variant burden tests rank gene signals?

In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!

🧬🧪🧵

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

This tells us that population structure itself, which does not contribute to "directional" allele frequency stratification, can't create fixed effects. What happens there is selection? well that I think is still an open question.
(8/8).

This makes PCs obsolete as a means to handle fixed genetic contributors. Of course, there are non-genetic contributors aligning with genetic factors so PCs might have role, but it has nothing to do with genetics.
(7/n)

Kinship estimation bias carries over to heritability estimation bias using variance components Abstract. Heritability is a fundamental parameter of diseases and other traits, quantifying the contribution of genetics to that trait. Kinship matrices ar

I greatly appreciate Ochoa group's long-lasting effort to define the quantity first and trying to estimate it. They've been stressing that PCs are unnecessary in LMMs are in fact harmful in certain cases. I have some thoughts.
(1/n)

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

Every time one anti-vaxxer is quoted in the media, one million scientists and healthcare workers should also be quoted in support of vaccines.

False equivalence in the media is killing us.

This developmental process could be a growth curve or any more involved process.

Surely part of variance in the developmental outcomes is driven by genetics and environment. The way I see this developmental process is more about how phenotypes are generated from genetic and environmental inputs, which act at every? stage of the process.

Love this thread. I like the developmental process concept to create a mental model of where variation is coming from. But, as with any process there are “factors” that drive its variance of outcomes.

I think what you are calling stochastic developmental variation is the outcome of unmeasured environmental perturbations and genetic-environmental interactions on a highly complex and possibly chaotic system, and definitely contributes to the observed non-genetic variance. :)

Is it possible to download the whole tree from the math genealogy project?

From the MapPorn community on Reddit: I made a map of the tides of Europe [OC] Explore this post and more from the MapPorn community

Parts of France and U.K. have large tide difference www.reddit.com/r/MapPorn/co... see also tidesandcurrents.noaa.gov/faq.html#08

Our work w/ two co-first authors Drew DeHaas and Ziqing Pan is now published. GRG allows large amounts of WGS polymorphism data to be analyzed in RAM via graph traversal & algebra operations & has some intrinsic connection w/ popgen data generating process & is different from ARG

IGD: A simple, efficient genotype data format Motivation While there are a variety of file formats for storing reference-sequence-aligned genotype data, many are complex or inefficient. Programming language support for such formats is often limit...

Our work (by Drew DeHaas) on an extremely simple yet efficient binary genotype format - designed to facilitate scalable bioinformatics tool development. www.biorxiv.org/content/10.1...

Fast Phenotype Simulation for Genotype Representation Graphs Motivation The Genotype Representation Graph (GRG) [[DeHaas et al., 2025][1]] is a graph representation of whole genome polymorphisms, designed to encode the variant hard-call information in phased wh...

Very proud of this manuscript with two talented undergraduate students, Aditya Syam and Chris Adonizio. We are continuing to push towards more scalable statistical genetics with Genotype Representation Graphs, and this is the start. www.biorxiv.org/content/10.1...

Method works from simple and complex scenarios in jointly estimating epoch time, population size, migration rate (symmetric or asymmetric), growth rate, and admixture proportion. Software integrated with msprime, demes, tsinfer/tsdate, relate, and singer. github.com/aprilweilab/...

Inference of complex demographic history using composite likelihood based on whole-genome genealogies Accurate parametric inference on complex demographic models is a continuing challenge in population genetics. Ancestral recombination graphs (ARGs) provide richer information than simple population ge...

Excited to preprint our latest work (w/ Drew DeHaas, Zhibai Jia, Leo Speidel) on using ARGs for demographic inference. w/ applications using data from 1000 Genomes Project. www.biorxiv.org/content/10.1...

Staff Scientist About EMBL-EBI EMBL’s European Bioinformatics Institute is a data powerhouse, utilised on a global scale to advance scientific discovery through bioinformatics and solutions to some of the world’s mos...

I am hiring! - looking for a Staff Scientist to co-run my research group with me. Staff Scientist is a senior professional scientist role at EMBL. Please forward to people you might know who could be interested! embl.wd103.myworkdayjobs.com/en-US/EMBL/j...

I want to try something again at #ASHG25 this year: I'll block some time on Thursday and Friday afternoons to meet with trainees who would be interested to chat on any topic.

I did this last year and it was great to meet a whole bunch of new people, at all career stages!

On ARGs, pedigrees, and genetic relatedness matrices Abstract. Genetic relatedness is a central concept in genetics, underpinning studies of population and quantitative genetics in human, animal, and plant se

Our paper (Brieuc Lehmann is the first author) is now online in Genetics.

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