Thread by @thatdnaguy

#ASHG21 JS: Jonathan Sebat.
a phenotypic spectrum of autisim attributable to... [ too fast I missed it ]

#ASHG21 JS: combined 3 cohorts. Two WGS cohorts and the SPARK study. 11k families. 37,375 individuals. Called with GATK best practices. Imputed genotypes from SPARK combined with PLINK. Calculated polygenic scores.

#ASHG21 JS: autism enriched in de novo mutations, rare inherited variants, and increased PRS scores.

#ASHG21 JS: Effect sizes for rare and common variant risk scores very similar in general. A female protective effect seen for common and rare variants.

#ASHG21 JS: See the same effect for rare and common variant PRS. More genetic load in females than males in both cases and controls.

#ASHG21 JS: inverse variation of rare variant and common variant risk. [ that's interesting ]

#ASHG21 JS: consistent with a liability threshold that differs by sex. All genetic risk factors contribute of variation across the phenotypic spectrum [i.e. different features or behaviors of the autism spectrum ]

#ASHG21 JS: De novo mutations have a strong effect on motor function, but the polygenic scores don't.

#ASHG21 JS: Do not see a constant male biased effect across phenotypes. Male biased effect on social communication. Other factors show some female bias. The parental age effect shows sex bias.

#ASHG21 JS: genetic basis of parental age is multifactorial. paternal bias of de novo mutation. maternal bias of PRS both rare and common with maternal age.

#ASHG21 JS: Look at 114 GWAS genes and 115 genes implicated by rare variant exome sets. But sets are enriched in fetal brain (cortex esp) categories. Most dramatic for the rare variant (rare, larger effect) genes.