Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank.
Chloe X Yap, Gail A Alvares, Anjali K Henders and 31 others
PMID 33568206WHAT IT FOUND
Genetic risk scores for autism were higher in the biobank cohort than in population controls, but did not predict individual diagnosis or autism severity.
Scores for IQ and sleep chronotype did predict those traits, though only in specific groups.
Key findings
01Participants with autism had significantly higher polygenic risk scores for autism than UK Biobank controls, but there was no significant difference between the autism group and the undiagnosed siblings or unrelated controls within the biobank.
02Polygenic risk scores for autism did not predict diagnostic status or autism-related phenotypes like ADOS severity, likely because the underlying genome-wide association study was underpowered.
03Polygenic scores for IQ predicted measured IQ in parents and undiagnosed siblings/controls, but showed no significant correlation with IQ in the autism group.
STILL TO COME
How it was doneWhat they found
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What it does not show
The sample size was relatively small, particularly for sibling and unrelated control groups, limiting the power to detect subtle genetic effects. The genome-wide association study used to calculate autism polygenic scores was underpowered, which likely explains the failure to predict individual diagnosis or severity. The unrelated control group had minimal exclusion criteria, potentially introducing heterogeneity that affects comparisons. CNV detection relied on SNP arrays rather than whole-genome sequencing, limiting resolution and sensitivity for rare variants.
Declared interests
Funded by the Cooperative Research Centre for Living with Autism, the National Health and Medical Research Council, the Australian Research Council, Mater Research, and the Mater Foundation.
The easy way to misread this
Do not interpret the higher average polygenic risk in the autism group as evidence that genetic testing can currently diagnose autism or predict severity in individual patients. The study explicitly states that autism polygenic scores failed to predict diagnostic status or phenotype severity, and the authors note the underlying genetic data was too underpowered for individual prediction.