The finding that autism has many causes (Happé and Ronald, 2008) should direct attention to improved means of differentially diagnosing its personalized bases. This process, in turn, centers on determining what adaptive neural and psychological systems has been altered, and how, to result in some set of autistic traits in some individual. Autistic phenotypes have been linked, for example, to increased protein synthesis at synapses (Bourgeron, 2009), higher excitatory to inhibitory neurotransmission (Rubenstein and Merzenich, 2003), enhanced local compared to global processing and connectivity (Happé and Frith, 2006), a bias toward systemizing over empathizing (Baron-Cohen, 2009), and enhanced perceptual functioning (Mottron et al., 2006).

Four studies have used data from the Psychiatric Genetics Consortium (PGC) on polygenic risk for autism (Cross-Disorder Group of the Psychiatric Genomics Consortium, 2013) to assess overlap of autism risk alleles (identified from over 5000 cases) with alleles for aspects of cognitive ability and intelligence. All four of these studies, which used diverse, independent populations and tests (or correlates) of cognitive abilities, have reported significant, substantial genetically-based positive associations of autism risk with intelligence, notably including full-scale IQ and a PCA-based measure of g (Clarke et al., 2015), childhood IQ, college attendance, and years of education (Bulik-Sullivan et al., 2015), cognitive function in childhood and educational attainment (Hill et al., 2015), and verbal-numerical reasoning and educational level reached (Hagenaars et al., 2016). These studies indicate that polygenic, small-effect size alleles that increased risk of autism are also associated with increased intelligence (and strong correlates of intelligence, such as education level; Davies et al., 2016) among neurotypical individuals.

Large brain size and head circumference, especially in childhood but also adulthood, represent some of the best-substantiated phenotypic correlates of autism (e.g., Fukumoto et al., 2011; Foster et al., 2015; meta-analysis in Sacco et al., 2015). Autism-linked increases in brain size have been shown to involve higher numbers of neurons (Courchesne et al., 2013), a thicker cortex (Hardan et al., 2006; Karama et al., 2011; Ecker et al., 2013; Smith et al., 2016), increased hippocampus volume (Barnea-Goraly et al., 2014; Maier et al., 2015), increased brain growth rates in early childhood (Campbell et al., 2014), increased rate of cortical thinning in adolescence (Hardan et al., 2009; Mak-Fan et al., 2012), a combination of “accelerated expansion in early childhood” with “accelerated thinning in in later childhood and adolescence” (Zielinski et al., 2014), and increased processing of more-local, detailed information (White et al., 2009).