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Genetic factors account for most of the risk of autism

New analysis of previous family study data estimates ASD heritability to be 83%

Louise Prime

Wednesday, 27 September 2017

A new analysis* of data from a previous study of the familial risk of autism spectrum disorder (ASD) has dramatically increased the estimate of its heritability, from about 50% up to 83%, meaning that genes might account for most of the risk for ASD. A separate new investigation has also found that having a sister with ASD is associated with greater additional risk than having a brother with ASD.

The authors of the research letter, published today in JAMA, said it has long been realised that ASD tends to aggregate in families. Previous research had estimated its heritability to be 50%. However, they argued that the methodology used in the original investigation from which this estimate is taken, which used a data set created to take into account time-to-event effects in the data, could have reduced the heritability estimates. So, they re-analysed the data underlying the original study, but using an alternative method to calculate the heritability of ASD – a method that, they pointed out, has been used by other studies in this area.

Those data came from a cohort of children born in Sweden between 1982 and 2006, and followed up for ASD until the end of 2009. Among these children were 37,570 twin pairs; 2,642,064 full sibling pairs; and 432,281 maternal and 445,531 paternal half-sibling pairs.

During follow up, ASD was diagnosed in 14,516 of these children. The researchers tested several models and, using the best-fitting one, estimated ASD heritability at 83% and non-shared environmental influence as 17%.

They commented: “This estimate [83%] is slightly lower than the approximately 90% estimate reported in earlier twin studies and higher than the 38% estimate reported in a California twin study, but was estimated with higher precision. Like earlier twin studies, shared environmental factors contributed minimally to the risk of ASD.”

The researchers pointed out that the method initially chosen for calculating heritability in the previous study led to a lower estimate of heritability of ASD. They explained: “The current estimate, using traditional methods for defining ASD discordance and concordance, more accurately captures the role of the genetic factors in ASD. However, in both analyses, the heritability of ASD was high and the risk of ASD increased with increasing genetic relatedness.”

Separate research,** published this week in JAMA Pediatrics, confirmed previous findings that boys have a notably higher risk of ASD than girls (overall prevalence 1.96% vs. 0.50%); and that ASD is more common among children with a sibling has ASD. But it also found that, for both boys and girls, having a sister with ASD appears to confer a greater additional risk than having a brother with ASD. The study authors reported: “When a male was associated with risk in the family, ASD was diagnosed in 4.2% of female siblings and 12.9% of male siblings; whereas when a female was associated with risk in the family, ASD was diagnosed in 7.6% of female siblings and 16.7% of male siblings.

They said: “Our study provides more specific guidance for the screening and counselling of families and may help inform future investigations into the environmental and genetic factors that confer risk of ASD.”


* Sandin S, Lichtenstein P, Kuja-Halkola R, et al. The heritability of autism spectrum disorder. JAMA 2017; 318(12): 1182–1184. doi:10.1001/jama.2017.12141.

** Palmer N, Beam A, Agniel D, et al. Association of sex with recurrence of autism spectrum disorder among siblings. JAMA Pediatr. Published online September 25, 2017. doi:10.1001/jamapediatrics.2017.2832.

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