Vaccines don't cause autism - so what does?

There isn't just science that shows it's not vaccines, there's science that shows in detail what the genetic causes are

In the wake of the rocky hearings for Robert F. Kennedy Jr.’s likely confirmation as Secretary of Health and Human Services this week, the question of whether autism is caused by vaccines continued to generate heated discussion. Kennedy would not say that he agreed that vaccines are not the cause, even when pressed by Senator Bill Cassidy who was seen as a swing vote. Cassidy later voted for Kennedy in committee, making his confirmation likely.

The evidence that vaccines do not cause autism is copious; here is an excellent roundup by STAT on many of the studies. Unfortunately, all that evidence doesn’t seem to be able to carry the day, mostly for reasons that have nothing to do with the evidence itself. Still, one thing to add into the mix is the answer to the question: if vaccines don’t cause autism, what does? Well, we know a lot about that.

There are many great papers on genome wide association studies in twins that show a large genetic contribution to autism, possibly as high as 90%. In addition, studies of brain tissue of autistic individuals of many ages allows for genetics studies on single cells. Last year, we published an extraordinary package of papers called PSYCHENCODE2 that took advantage of a large repository of brain tissue samples in analyzing single cells for multiple neurodevelopment conditions.

Here is one of those papers on autism:

Title: Molecular cascades and cell type–specific signatures in ASD revealed by single-cell genomics

Authors: BRIE WAMSLEY, LUCY BICKS, YUYAN CHENG, RIKI KAWAGUCHI, DIANA QUINTERO, MICHAEL MARGOLIS, JENNIFER GRUNDMAN, JIANYIN LIU, SHAOHUA XIAO, NATALIE HAWKEN, SAMANTHA MAZARIEGOS, AND DANIEL H. GESCHWIND

Here’s the abstract:

Genomic profiling in postmortem brain from autistic individuals has consistently revealed convergent molecular changes. What drives these changes and how they relate to genetic susceptibility in this complex condition are not well understood. We performed deep single-nucleus RNA sequencing (snRNA-seq) to examine cell composition and transcriptomics, identifying dysregulation of cell type–specific gene regulatory networks (GRNs) in autism spectrum disorder (ASD), which we corroborated using single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) and spatial transcriptomics. Transcriptomic changes were primarily cell type specific, involving multiple cell types, most prominently interhemispheric and callosal-projecting neurons, interneurons within superficial laminae, and distinct glial reactive states involving oligodendrocytes, microglia, and astrocytes. Autism-associated GRN drivers and their targets were enriched in rare and common genetic risk variants, connecting autism genetic susceptibility and cellular and circuit alterations in the human brain.

Single-cell genomics reveals cell type–specific and laminar changes in ASD: These changes prominently affect layers 2 and 3 interhemispheric and callosal-projecting excitatory (Ex) neurons, superficial SST interneurons, and reactive glial states in the frontal cortex (FC). By defining gene regulatory networks (GRNs; red, up-regulated; blue, down-regulated) and integrating them with ASD genetic risk variants, we discerned candidate drivers of the transcriptional changes and genetic susceptibility acting in specific cell types. OPCs, oligodendrocyte progenitor cells; INTs, inhibitory neurons; WM, white matter; DEGs, differentially expressed genes.

So, not only do we know what happens with all these genes, but we can see it in single cells in brains. For the people who want to “see the data,” we really hope they’ll take a look. Spoiler alert: we have the data.

As always, if you see something in the paper that doesn’t seem right, let us know at science_data@science.org.