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Last but definitely not least is our Neurodiverse Advisory Committee (NAC) consisting of autistic citizens and scientists. In partnership with autismtreeproject.org we have assembled the NAC to provide us with the stakeholders perspective on autism research!

autismtreeproject.org

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We will also investigate how environmental factors influence clinical outcome of genes in ASD. Samples of many thousands are needed to identify G. Capturing the effects of GxE requires sample sizes of millions. Juicy preliminary data will be posted soon to medrxiv. It takes a village, come join us!

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As a novel approach to causal inference, we will use collider effects to find genetic evidence to SUPPORT a causal role of environmental exposure. If E has a strong effect that is uncorrelated with G in the population, genes will explain LESS of the variance in the explosed group!

Our 2022 paper in NG illustrates one example: the observed association of parental age with ausism consists of a mixture of causal pathway E → de novo mutation → ASD; and noncausal pathway Parental age ← polygenic score → ASD

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We will use a multi-pronged approach to causal inference using data on G and E in >2 million people, including association, MR and GxE exploring the interplay of exposures with rare and common variation that contributes to ASD, and we will rigorously evaluate rGE in family and population

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THE major challenge in epidemiological studies of the environment in autism is the pervasive passive correlation of genes and environment (rGE) that happens in the population, also known horizontal pleiotropy. There are causal effects to be found, but we need to separate correlation from causation

Jonathan Sebat @sebatlab.bsky.social · 26/09/2025

Autism has a strong genetic basis, 100 genes have been identified and we e have multiple independent genetic predictors that have very strong signals in the population. If you are going do and epidemiological study of E, you need to account for G and GxE! pmc.ncbi.nlm.nih.gov/articles/PMC...

pmc.ncbi.nlm.nih.gov

A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex

The genetic etiology of autism spectrum disorder (ASD) is multifactorial, but how combinations of genetic factors determine risk is unclear. In a large family sample, we show that genetic loads of rar...

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Jonathan Sebat @sebatlab.bsky.social · 26/09/2025

We are proud to be one of the 13 projects funded by the NIH Autism Data Science Initiative. Our project: "Elucidating the Interplay of Genes and Environment in Autism Using Genomic and Exposure Data from Large Populations" 🧵https://www.nytimes.com/2025/09/26/health/autism-research-trump-kennedy.html

nytimes.com

Despite False Claims, Trump Funnels Millions Into Credible Autism Research

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Jonathan Sebat @sebatlab.bsky.social · 19/09/2025

Today's ACIP meeting had a presentation on the genetics of myocarditis following COVID vaccine based on Whole exome sequencing of 50 cases. See time stamp 2:26 www.youtube.com/live/_9ChY9S...

youtube.com

Advisory Committee on Immunization Practices (ACIP) - September 19, 2025 – Day 2 of 2

YouTube video by Centers for Disease Control and Prevention (CDC)

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Jonathan Sebat @sebatlab.bsky.social · 15/09/2025

Pfff, big deal. My social media accounts are powered by edibles

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Jonathan Sebat @sebatlab.bsky.social · 01/09/2025

If it’s not an exaggeration, and if the shoe fits, wear it. Worst case scenario, someone might actually read your paper

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Reposted by Jonathan Sebat

MwahahahahahadScientist @mads100tist.bsky.social · 30/08/2025

This is it. I cannot explain it, but this is it. This is how -and why- we should be doing science

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Jonathan Sebat @sebatlab.bsky.social · 16/08/2025

Bad ass mom of the year 🤘. This was NOT an easy coffee ride. This was the Saturday Cadence Cyclery ride in SD.

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Reposted by Jonathan Sebat

Brain and Mind Centre @brainandmindcentre.bsky.social · 11/06/2025

Great turnout! Decoding Genetics of Autism Speakers: Prof Jonathan Sebat - UCSD Prof Lilia Lakoucheva - UCSD Dr. Alan Ma - Children’s Hosp Westmead, Prof. Katrina Williams - @MonashUni Hosted by BMC/Child Neurodevelopment team @adamguastella.bsky.social

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Reposted by Jonathan Sebat

Hank Green @hankgreen.bsky.social · 28/07/2025

I doubt that there is a single family in America that hasn’t benefitted directly from the NIH.

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Jonathan Sebat @sebatlab.bsky.social · 28/07/2025

True story, as an undergrad I did an experiment with green Anole lizards where I kept a constant number of flies in their cage by running a hose from my scuba tank through a jar of flies and into the tank. Lizards really are the mothers of invention

Jonathan Sebat @sebatlab.bsky.social · 28/07/2025

Leaf blowers on lizards is pretty innovative if you ask me

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Jonathan Sebat @sebatlab.bsky.social · 28/07/2025

Not the most accurate analogy. In this example there is a real difference between the 4th percentile and the 15th percentile

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I'm pretty sure that there would not be any context in my chatGPT conversations in which the chatbot would inclined to say "Hail Satan". I'm really missing out.

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Agreed. Theres alot to learn from single cell LR-WGS of somatic tissues!

TL;DR LRs boost detection of de novo and inherited coding SVs and longer TRs, which boosts detection of causal variants. But long reads are game changer WRT to resolving complex genetic variation and its functional consequences and regulatory effects.

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Power is limited in N=243. But the signal is quantifiable. Rare SVs, TRs and rare SNVs combined explained 7.6% of the heritability. We will need larger samples to get precise estimates, but the combined common and rare is starting to reach a substantial fraction.

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Gray zone carriers typically look like panel E. Only FMR1 methylation is skewed. X chromosome inactivation is not skewed. The one exception (panel D) was a girl that carried an X-linked dominant mutation in DDX3X a gene that escapes XCI and, for unknown reasons, is know to cause skewed XCI

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Skewed methylation was a characteristic of all "gray zone" alleles of FMR1 (>35 repeats). But in all but one sample, the skewing was specific to FMR1. X chromosome inactivation was NOT skewed. 10/N

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In the fragile X repeat FMR1, we went full long-read nerd with PHASED repeats AND methylation. Phased reads in one female (REACH365) shows random methylation (red) on the X. In another female (REACH561) with an expanded 49 repeat allele, methylation was totally skewed to expanded haplotype H2 9/N

Where long reads really shine is when you need to map out and assemble large complex SVs. In doing so, we found a class of duplication/deletion events (TAN-DUP-DEL and INV-DUP-DEL) events. They also produce distinct signatures in short read coverage data

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Phase information of individual reads ends up being useful for a variety of purposes including assembling SVs, genotyping and detection of de novo and mosaic SVs and TRs (more to come on this) 6/N

De novo SVs have been bread-and-butter of ASD genetics, and LRs detect novel de novo and somatic MOSAIC coding SVs. In this example, a de novo in-frame duplication, was present on most (but not all) reads on the H2 haplotype in the offspring and coverage also showed copy number of 2.5 instead of 3.

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