Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.
Rui Chen, Lea K Davis, Stephen Guter and 7 others
PMID 28344757WHAT IT FOUND
When autism families were split by blood serotonin, genes hit by new variants in probands with normal serotonin lined up with known autism risk genes; genes in high-serotonin probands lined up with a different biological group.
No treatment or clinical test was studied.
Key findings
01In the 116 analysed families, no gene had recurrent loss-of-function de novo variants, but combining these variants with larger autism datasets supported USP15, FOXP1 and KDM5B as candidate autism genes.
02In the 67 normal-serotonin and 30 high-serotonin probands, loss-of-function de novo genes in the normal group were enriched in known autism risk gene sets, while the high group showed no enrichment there but network enrichment with DAWN-1.
03Rare recessively acting variant burden did not differ between probands and parents, but recessively acting genes in the high-serotonin group were enriched in a 33-gene autism risk list, including ETFB and RELN.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
The sample was small for gene discovery, and no gene had recurrent loss-of-function de novo variants within the 116 analysed families. The serotonin groups used cut-points of z-score above 1.75 and below 1, and 10 probands with scores between 1 and 1.75 were not used in group comparisons. The authors reported nominal p values without correcting for multiple testing, so some gene set results may be unstable. The recessive-variant analysis was restricted to a Western European subset, and this made the sample smaller. The study did not test therapy, communication, motor, sensory, or functional outcomes, so it cannot guide clinical treatment. Some recurrence findings depended on combining these variants with external autism sequencing datasets.
Declared interests
Funders named were the National Institutes of Health and the Center for Inherited Disease Research.
The easy way to misread this
Do not read this as evidence that blood serotonin testing can guide autism therapy. The study used serotonin to group families for genetic discovery, and it did not test communication, motor, sensory, or treatment outcomes.