Angelica Ronald

@angelicaronald.bsky.social

Professor of Psychology and Genetics at University of Surrey

PGS explain 3-6% of variance in walking. 11 GWS independent loci. Effect sizes range from 0.06 months to 0.23 months. One locus associated with RBL2 via eQTL. Associated with Brunet-Wagner (hypotonia, motor impairments, unsteady or absent walking).

Age of onset at walking - varies between 8-18 months. Complex and highly heritable. Combines a lot of different factors (motivation, muscles, coordination). Delays are often viewed as a red flag.

Now Geli Ronald will talk about a genome wide association study of age at onset walking. Why study this age? Critical period for environment, rapid onset of developmental milestones and brain changes. Arguably under appreciated in common variant genetics.

(8/9) To conclude, due to inconsistent associations and limited generalizability, we underscore that the autism polygenic score does not have clinical utility and should only be applied for scientific purposes, with improvements needed for a deeper understanding of autism’s polygenic underpinnings

(7/9) We show that the autism polygenic score, as a standalone variable associates consistently with autism diagnostic status but is unable to capture the spectrum’s complex phenotypical and etiological differences and its genetic overlap with other traits and conditions.

(6/9) Associations with outcomes other than those mentioned above were inconclusive and effect sizes generally small (median r = 0.03). Hence, our results suggest the autism polygenic score may lack the statistical power to adequately capture polygenic effects.

(5/9) Our systematic review also revealed evidence for associations with social behavior, depression, motor skills and physical activity, although these results show incongruency over samples.

(4/9) A meta-analysis of nine studies revealed strong evidence for an association between the autism polygenic score and autism diagnosis in independent cohorts (meta-analytic r = 0.158 (95% CI 0.067 – 0.249)), which supports the polygenic score’s specificity.

(2/9) 🧬Genetic factors play a substantial role in the etiology of autism and its co-occurrence with other conditions and traits. We aimed to clarify the associations between the autism polygenic score and autism diagnosis, autistic traits, and related behavioral and neurobiological traits

Very excited about this important piece of work with @angelicaronald.bsky.social characterising gene associations with age of walking onset. We also show using dHCP data that these are related to volume in key brain motor regions (like the deep grey nuclei and cerebellum) even as a newborn infant

Angelica Ronald@angelicaronald.bsky.social · last yr.

Our gene discovery project on age at onset of walking is out today! Find the paper here www.nature.com/articles/s41... Huge thanks to the cohorts, collaborators & coauthors, in particular first author Dr Anna Gui 1/n