Varun Warrier

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...

Excited to share our latest work on the factors that determine what genes we find (and don't find!) in GWAS and burden tests.

We describe a critical concept that we call *specificity*.

Led by Jeff Spence and Hakhamanesh Mostafavi:

Study reveals genetic and developmental differences in people with earlier versus later autism diagnosis Researchers find different genetic profiles related to two trajectories that autistic children tend to follow. One linked to early diagnosis, and communication

And an article for the general public by @universitypress.cambridge.org

www.cam.ac.uk/research/new...

Early- and late-diagnosed autism are genetically distinct Analyses of symptoms and genomic data indicate that autism that manifests in early childhood is distinct from autism that is diagnosed later in development.

And a very helpful and informative commentary on the paper by @tuckerdrob.bsky.social www.nature.com/articles/d41...

Polygenic and developmental profiles of autism differ by age at diagnosis - Nature A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

This was a fantastic collaboration with lots of people including @hilarycmartin.bsky.social @jakobgrove.bsky.social, Experts by Experience, and several others who I can't seem to find on this app.

Article: www.nature.com/articles/s41...

I add that earlier and later diagnosed autism are not valid diagnostic terms and what we are looking at is (one) gradient. Also genetics explains only a fraction of the variance, with most studied factors explaining < 10%. We have FAQs in the Supplementary where we address common questions.

Furthermore, the later diagnosed autism genetic factor is genetically more correlated with ADHD, depression, and PTSD, suggested complex gene-environment correlations and an urgent need for support.

In work led by the talented Xinhe Zhang out today in Nature, we challenge this idea. We show the developmental and genetic profile of autism differs substantially by age at diagnosis. Later diagnosed autism is not a milder version, but a different version who need acceptance and support.

It is now clear that more people are being diagnosed as autistic in their teens and as adults than in childhood. A prevailing theory is that those diagnosed later have "milder" form of autism, and later diagnosis entirely due to social factors.

🧬💥 Do the genetics that make you develop a disease also help you survive it? Not much.

Our new study in Nature Genetics including 9 disease and 7 biobanks shows:

• Susceptibility variants ≠ survival
• PRSs for onset weak at predicting progression
• Lifespan PRS predicts survival better

We are delighted to announce the launch of a new Master's Programme in Brain Health and Disease within the Department of Clinical Neurosciences at the University of Cambridge.

Applications are now open!

@camneurodept.bsky.social

www.clinical-neuroscience.cam.ac.uk/education/ta...

Ah yes, of course! I agree :)

Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations - PubMed The offspring of older fathers have higher risk of psychiatric disorders such as schizophrenia and autism. Paternal-age-related de novo mutations are widely assumed to be the underlying causal mechani...

Although, there is a lot of genetic confounding with parental age associations: increased genetic likelihood for autism -> finding a partner later in life -> having children later in life.

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

pubmed.ncbi.nlm.nih.gov/27213288/

We have an opening for a research assistant/associate to study the genetics of neurodevelopmental traits in the general population, and explore their overlap with neurodevelopmental diagnoses. Funds available until Jan 2027.

lnkd.in/eHEcccwC

Please circulate widely.

We are excited to share GPN-Star, a cost-effective, biologically grounded genomic language modeling framework that achieves state-of-the-art performance across a wide range of variant effect prediction tasks relevant to human genetics.
www.biorxiv.org/content/10.1...
(1/n)

Very nice method that exploits collider bias to identify independent contributors to outcomes.

Latest processing of UK Biobank brain imaging data - now with 82,000 usable first-scan datasets. Correlating brain IDPs with 13,000 non-imaging variables gives a rich manhattan-stye plot. 324,000 Bonferroni-significant associations.

Isn't genetics cool???

Within only 145 nucleotides(!) of a non-coding RNA (RNU4-2) - different variants in distinct regions / structures cause three distinct disorders!!! (all discovered within the last 18 months)

🤯🤓🧬❤️

Higher eQTL power reveals signals that boost GWAS colocalization Expression quantitative trait locus (eQTL) studies in human cohorts typically detect at least one regulatory signal per gene, and have been proposed as a way to explain mechanisms of genetic liability...

Excited to share this preprint from first author Jon Rosen, a postdoctoral fellow in the @klmohlke.bsky.social lab and my lab. We examine eQTL study sample size and how this affects signal discovery and rates of colocalization with GWAS.

www.biorxiv.org/content/10.1...

Interested in Network hubs, cortical hierarchies, and gradients? Ever wonder where they come from? Check our latest review, where we cover different approaches to mapping hubs, models for their evolution, and mechanisms for how they develop:

osf.io/preprints/os...

ECR Workshop: Proteomics & Mental Health 🧠
9 Oct | Edinburgh | £25

Hosted by @mqmentalhealth.bsky.social & @datamind.bsky.social in partnership with MHP.

Meet the Speakers! Programme & bios online – register: rebrand.ly/ecr-workshop

Science doesn’t need to be pretty and go according to plan; it just needs to lead to a discovery. If doesn’t have to be done alone or together with someone else; there just needs to be a discovery. It doesn’t need to happen fast or slow; just as long as there’s a discovery, then everybody is happy.

Our new paper is out today! 🎉 In it, we use administrative register data to document how psychiatric disorders are strongly linked to parental income, from childhood far into adulthood. Furthermore, we attempt to separate causation and selection using kinship-based models.
doi.org/10.1111/jcpp...

Psychiatric Genetics Beyond Heritability: Q&A with Michel Nivard We look for genes as a means to an end—biology, epidemiology, and etiology of complex human outcomes.

Psychiatric Genetics Beyond Heritability: Q&A with Michel Nivard ( @michelnivard.bsky.social )

“We look for genes as a means to an end—biology, epidemiology, and etiology of complex human outcomes.”

www.psychiatrymargins.com/p/psychiatri...

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...

🚨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 🧵👇

Antecedents and outcomes of a late attention deficit hyperactivity disorder (ADHD) diagnosis in females Females receive an attention deficit hyperactivity disorder (ADHD) diagnosis at an older age than males. We examined the antecedents and outcomes of later (age 12+) diagnosis in females using data fro...

New pre-print! ✨ Antecedents and outcomes of a late ADHD diagnosis in females: www.medrxiv.org/content/10.1...

TLDR: This study finds evidence that a delay in ADHD diagnosis has profound and clear consequences by adolescence and this disproportionately disadvantages females (people who are AFAB).

The Contribution of Common and Rare Genetic Variation to Emotional and Behavioural Symptoms in Childhood and Adolescence Genetic factors influence vulnerability to common mental health conditions, but their role in early-life mental health remains understudied. We analysed genotype array and exome sequence data from two...

New preprint!🚨
"“The Contribution of Common and Rare Genetic Variation to Emotional and Behavioural Symptoms in Childhood and Adolescence” is out on medRxiv.
www.medrxiv.org/content/10.1...

Thread 👇

Studying the genetics of intelligence measures can help us understand the neurobiology of cognition and neurodevelopmental conditions 🧬🧠

We estimated missing intelligence test scores in @ukbiobank.bsky.social to reduce bias and boost power.

Preprint: www.medrxiv.org/content/10.1...

Thread 👇

NHS England » NHS England responds to ADHD Taskforce interim report An independent taskforce set up to tackle challenges in attention deficit hyperactivity disorder (ADHD) care has published its interim report and recommendations today (Friday 20 June 2025). The repor...

I am proud to have led and contributes to the experts in evidence advisory group- alot of hard work went into this www.england.nhs.uk/2025/06/nhs-...