Illustration by Laurène Boglio

Many tweets in the autism research space this week discussed a study exploring the role of rare variants in 22 complex traits. The work, published earlier this month in Nature, featured “a new method and insights from nearly 400,000 exomes,” tweeted study investigator Daniel Weiner, a graduate student in Elise Robinson’s lab at Harvard Medical School.

How will rare genetic variation inform our understanding of common disease?

Today in @Nature, we’re excited to share our answer to this question,

with a new method and insights from nearly 400,000 exomes:https://t.co/H3gXTSK6IC

???? (1/15):

— Dan Weiner (@danweiner92) February 8, 2023

The researchers developed tools to glean heritability and genetic correlations from exome-sequencing data and found that, on average, rare variants contribute to about 1 percent of the 22 traits’ heritability, compared with 13 percent for common variants, Weiner explained.

Genome-wide association studies (GWAS) have long shown how common genetic variants contribute to complex human traits and disease. The new work suggests that “rare variants are enriched in the same candidate genes identified by GWAS,” noted Todd Brusko, professor of pathology, immunology, and laboratory medicine at the University of Florida in Gainesville.

An important paper regarding rare vs common variants for complex diseases like diabetes. One important take away-rare variants are enriched in the same candidate genes identified by GWAS. https://t.co/HYf40QBdG6

— Todd M. Brusko (@Bruskolab) February 9, 2023

In a tweet summarizing the paper’s takeaways, Stephen Waggoner, associate professor of pediatrics at Cincinnati Children’s Hospital in Ohio, wrote, “Rare coding variants will contribute only modestly to missing heritability and population risk stratification.”

Rare coding variants will implicate a tractable number of large-effect genes, common & rare associations are mechanistically convergent, and rare coding variants will contribute only modestly to missing heritability and population risk stratificationhttps://t.co/kkD38646Ad https://t.co/PSR2fsVEcQ

— Waggoner Lab (@LabWaggoner) February 8, 2023

Even so, Weiner tweeted that he and his colleagues remain “optimistic about rare variants informing understanding of common disease biology.”

???? Reason 1: Common + rare variants = convergent:

Drugs targeting RV associated genes can benefit many patients, not only the few who carry specific mutations

???? Reason 2: RV genetic architecture less polygenic -> Disease mechanisms involve attainable number of genes

(14/15)

— Dan Weiner (@danweiner92) February 8, 2023

Another paper turning heads on Twitter this week explored how reactive microglia adjust their microtubule cytoskeleton, which entails “remodeling from acentrosomal to centrosomal arrays,” tweeted the study’s lead investigator Francesca Bartolini, professor of biochemistry at Columbia University.

Best Valentine gift ever????! A wonderful journey in collaboration with @SAngelantonio team and many others without whom this work would have not been possible????
Microglia reactivity entails microtubule remodeling from acentrosomal to centrosomal arrays https://t.co/lfXonZfANI

— Bartolini Lab (@BartoliniLab) February 14, 2023

When microglia become reactive in response to inflammation or injury, they change their shape dramatically. Spectrum has previously covered the link between autism and microglia and microtubule biology.

Ghazaleh Eskandari-Sedighi, a postdoctoral researcher at the University of Alberta in Canada, tweeted that it’s great to see how this work connects her first love from when she started studying the brain — microtubules — with her most recent one: microglia.

Microtubules were the first proteins I started my adventurous journey of studying brain with, and ever since then I’ve been closely tracking the amazing work of @BartoliniLab. It’s great to see how their latest work connects my first love with the most recent one (microglia)! https://t.co/Pf5LOcZoqM

— Ghazaleh Eskandari-Sedighi (@GhazalehEsk) February 14, 2023

Meng-meng Fu, assistant professor of cell biology, development and physiology at the University of California, Berkeley, called the paper a “must read for microtubule and microglia enthusiasts.”

Golgi outposts in microglia!

Must read paper for microtubule and microglia enthusiasts alike ???? https://t.co/hwbztI4OE1

— Meng-meng Fu (@Meng2Fu) February 14, 2023

Lastly, scientists weighed in on Spectrum’s Deep Dive about how remote autism assessments developed during the COVID-19 pandemic may help solve a persistent problem: the long wait families endure to get a diagnosis in the United States.

“Great reading about Telehealth development assessments,” tweeted Adam Guastella, professor of child and youth mental health and a clinical psychologist at the University of Sydney in Australia. “The next 5 years will see new innovative approaches transforming the science of assessment that overcome disadvantage, isolation and cost for families.”

Great reading about Telehealth development assessments @Spectrum

The next 5 years will see new innovative approaches transforming the science of assessment that overcome disadvantage, isolation and cost for families@becsutherlandSP @alistair_mcewan https://t.co/mj5R7rdFQ7

— Adam Guastella (@Adam_Guastella) February 15, 2023

But others cautioned that telehealth should not replace in-person evaluations entirely. “It may be a useful additional adjunct, but there is so much more to holistic assessment,” tweeted Michael Absoud, honorary reader in women and children’s health at King’s College London in England.

I worry about this replacing in person assessments— it may be a useful additional adjunct, but there is so much more to holistic assessment…

— Michael Absoud (@MAbsoud) February 15, 2023

That’s it for this week’s Community Newsletter! If you have any suggestions for interesting social posts you saw in the autism research sphere, feel free to send an email to [email protected].

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Cite this article: https://doi.org/10.53053/RYHL4670