ASDs are a group of neurodevelopmental conditions characterized by impairments in social interaction, communication, and by restricted repetitive behaviors and interests (American Psychiatric Association, 2000). Diagnosis usually occurs in childhood and ASD diagnoses are usually extremely stable across the lifespan. The previous edition of the diagnostic statistical manual (DSM-IV, American Psychiatric Association 2000) distinguished the ASD subtypes autistic disorder, Asperger syndrome, and pervasive developmental disorder not otherwise specified (PDD-NOS). I The new DSM-5 edition, folds several subtypes into a single group called “autism spectrum disorder” (see www.​dsm5.​org). ASDs are more common in males, with a male to female ratio of about 4:1 (Fombonne, 2006), and they can occur in individuals across the full range of cognitive ability from very low to very high IQ (Fombonne, 2006).

It is well established that twin studies of narrowly defined autism reported monozygotic (MZ) twin pairs to be more similar than dizygotic (DZ) twins in their concordance for autism (Bailey et al., 1995; Folstein & Rutter, 1977; Ritvo, Freeman, Mason-Brothers, Mo, & Ritvo, 1985; Steffenburg et al., 1989). Table 2.1 outlines the twin studies of narrowly defined autism and ASD. In the original Folstein and Rutter study including 21 twin pairs (11 MZ and 10 DZ pairs) (Folstein & Rutter, 1977), MZ twins, who share all of their genes, were 36 % concordant—that is, in just over a third of pairs both twins had autism. In DZ twins, who share on average half their DNA, there was 0 % concordance—that is, all twin pairs were discordant for diagnosis: one had autism, the other did not. The concordance rates were not found to be explainable by biological hazards associated with the twins’ birth. Model fitting in a later paper estimated the heritability of autistic disorder as 91–93 % (Bailey et al., 1995). It was also found that when criteria were widened to include individuals who show some but not all of the features of autism, this “broader autism phenotype” (BAP, as described by Folstein & Rutter, 1977), the MZ concordance increased to 92 % and the DZ concordance increased to 10 %, respectively (Bailey et al., 1995) (see Table 2.1).

Since the twin studies of narrowly defined autism, there have now been four twin studies incorporating all autism spectrum disorders (see Table 2.1). The first two twin studies of ASDs reported high MZ concordances (88–95 %) and DZ concordances of 31 % (Rosenberg et al., 2009; Taniai, Nishiyama, Miyachi, Imaeda, & Sumi, 2008). These DZ concordances for ASD are notable for being higher than in any previous twin studies of autism, whereas the MZ concordances are similar to those reported in some of the previous studies. The first ASD twin study employed a sample of children with ASD from Japan who were diagnosed using DSM-IV criteria (Taniai et al., 2008). Because no structured interview was available in Japanese, the children were diagnosed using semi-structured summaries (case vignettes) of all available psychiatric and diagnostic information. Using the Childhood Autism Rating Scale as a quantitative assessment of autistic symptoms, this study reported heritability estimates of 73 % for males and 87 % for females. It is unknown how diagnoses made by case vignettes in Japan compare to the standard Western diagnostic instruments. Apart from methodological differences there may also be subtle cultural differences in the expression, diagnostic practice, and prevalence of ASDs (Grinker, 2007; Grinker et al., 2012; Kim et al., 2011). The second ASD twin study relied on parent report of ASD diagnoses through a US-based voluntary online register (Rosenberg et al., 2009). This is a less systematic or reliable ascertainment method than employed in the previous twin studies, but has the advantage of giving a large sample size (with 277 twin pairs it is the largest twin study of ASD published so far). The twin concordances from this second ASD twin study (MZ, 88 %; DZ, 31 %) are highly similar to those from the first ASD study from Japan, described above.

Finally, the more recent third and fourth twin studies of ASD are notable for having both relatively large and systematically obtained population samples from Sweden and California, respectively. Both studies reported concordances as well as liability threshold model-fitting analyses (Hallmayer et al., 2011; Lichtenstein, Carlström, Råstam, Gillberg, & Anckarsäter, 2010). In the Swedish study, the concordances for all ASDs (the measure did not distinguish different types of ASD) were 39 % for MZ twins and 15 % for DZ twins; liability model-fitting analyses suggested a heritability of 80 %, thus again indicating strong genetic influences on ASD (Lichtenstein et al., 2010). The Californian study (Hallmayer et al., 2011) distinguished strict autism from broader ASD and reported MZ and DZ twin concordance rates that were largely similar to previous studies. For narrowly defined autism, the MZ vs. DZ concordance rates were 58 % vs. 21 % (males) and 60 % vs. 27 % (females), compared with 77 % vs. 31 % (males) and 50 % vs. 36 % (females) for broader ASD. These concordance rates are remarkably similar to the rates reported by Rosenberg et al. (2009) and Taniai et al. (2008), with the exception of the relatively low concordance for broad ASD in MZ females (although the confidence intervals around this estimate were large due to limited sample size). Despite the similarities in concordance rate findings, the liability threshold model-fitting analyses employed by Hallmayer et al. (2011) produced a more modest heritability (37 % for autism and 38 % for ASD) and a large shared environmental component (55 % for autism and 58 % for ASD; Hallmayer et al., 2011). This is the first and only twin study to report substantial shared environmental influences on diagnosed autism or ASD. The contrasting results from this Californian twin study compared to all the other twin studies of autism and ASD that have included model-fitting analyses—in particular the finding of a large shared environmental component—require further explanation. Possible reasons for the different results in this study may involve the characteristics of the Californian twin sample or the specific assumptions employed in the modeling, including the ascertainment probability. The participation rate in this study was only 17 %, and although the authors could rule out various sources of potential ascertainment bias, it remains a question whether the sample under study was a true reflection of the Californian population as a whole. A notable characteristic of the Californian study was its use of the autism diagnostic observation schedule (ADOS) and autism diagnostic interview-revised (ADI-R) diagnostic tools to identify cases. The ADOS involves observational assessments of behavior, and the combination of these two instruments has come to be considered one of the most well-respected methods of diagnosing ASD in recent years.

In sum, since the original twin studies showed the high heritability of autistic disorder, three new studies have reported twin concordances or model-fitting results to suggest a high heritability for ASD, while one study has suggested that shared environment may play a prominent role in ASD.

Findings from broader autism phenotype studies in first-degree relatives of people with autism (Sucksmith et al., 2011) revealed that these relatives may show elevated rates of behavioral and personality traits characteristic of ASDs. Quantitative scales assessing these so-called autistic traits, such as the Childhood Autism Spectrum Test (CAST; Williams et al., 2008), Autism-Spectrum Quotient (AQ; Baron-Cohen, Wheelwright, Skinner, Martin, & Clubley, 2001), and Social Responsiveness Scale (SRS; Constantino, 2002), are continuously distributed in community samples throughout the normal range to the clinical extreme and show high internal consistency (e.g., Hoekstra, Bartels, Cath, & Boomsma, 2008; Skuse, Mandy, & Scourfield, 2005). Relatives of individuals with ASDs show, on average, elevated levels of autistic traits compared to control families (e.g., Bishop, Maybery, Wong, Maley, & Hallmayer, 2006; Constantino et al., 2006) suggesting that subclinical autistic traits share familial influences with diagnosed ASD. Since common genetic variants (that are, by definition, present in a significant proportion of the general population) are thought to play a role in the etiology of autism (e.g., Alarcón et al., 2008; Anney et al., 2010; Ronald, Butcher, et al., 2010; Wang et al., 2009; Weiss et al., 2009), it is argued that understanding the etiology of individual differences in autistic traits in the general population may aid our understanding of the causes of clinically diagnosed autism.

Table 2.2 describes twin studies of autistic traits assessed in general population and community samples. These studies report that autistic traits, as assessed using quantitative scales such as the CAST, AQ, and SRS, show heritability estimates ranging from 36 to 90 % in twin samples ranging from age 2 to age 18. The general trend is for heritability to vary between 60 and 90 % for parent- and teacher-rated autistic traits in middle childhood and older (Constantino & Todd, 2000, 2005; Lundström et al., 2012; Robinson et al., 2011; Ronald, Happé, Bolton, et al., 2006; Ronald, Happé, & Plomin, 2005; Ronald, Happé, & Plomin, 2008; Skuse et al., 2005), with self-report assessments of autistic traits giving more moderate heritability estimates (32–57 %; Hoekstra, Bartels, Verweij, & Boomsma, 2007; Lundström et al., 2011; Ronald, Happé, et al., 2008). The two twin studies of early childhood, on 2-year-olds, also reported moderate heritabilities (40 and 44 %) of parent-rated autistic traits (Edelson & Saudino, 2009; Stilp, Gernsbacher, Schweigert, Arneson, & Goldsmith, 2010).

Shared environmental influences are the environmental influences common to both twins that make children growing up in the same family more similar. Some studies in middle-to-late childhood report modest shared environmental influences ranging from 10 to 32 % (Constantino & Todd, 2000, 2003, 2005; Ronald, Happé, et al., 2008), but the majority find no significant effects (see Table 2.2). All studies report modest to moderate influences of the nonshared environment, defined as environmental influences that make children growing up in the same family different, and which by default include measurement error in their term.

Twin research has demonstrated the magnitude of the role of both genetic and environmental influences on autistic traits across development, both measured in the general population and in the extremes of this population. Extremes analyses (presented by Lundström et al., 2012; Robinson et al., 2011; Ronald, Happé, Price, Baron-Cohen, & Plomin, 2006; see Table 2.2) consistently suggest that there is a genetic link between ASDs, impairments at the quantitative extreme of the distribution of autistic traits, and variation in autistic traits in the general population. For example, in a recent UK study, the high heritability of autistic traits at age 12 did not differ for extreme 5, 2.5, and 1 % quantitatively defined extreme-scoring groups (Robinson et al., 2011). In a Swedish sample, similar findings were reported and cross-twin cross-cut-off correlations suggested considerable genetic overlap across varying severity thresholds for autistic symptoms (Lundström et al., 2012).

In sum, twin studies of autistic traits have been important in supporting the notion of autism as a continuously distributed trait, a position that has been championed by a number of autism researchers (Baron-Cohen et al., 2001; Constantino & Todd, 2003; Gillberg, 1992; Hoekstra et al., 2008; Ronald, Happé, Bolton, et al., 2006; Ronald & Hoekstra, 2011; Skuse et al., 2005).

Twin studies of autism, broader ASDs, and autistic traits consistently demonstrate that nonshared environment plays a modest but potentially important causal role. MZ twins are not 100 % similar on autism, broader ASDs, BAP, or autistic traits. The most effective way to identify nonshared environmental influences is to employ an MZ differences design. Because MZ twins are genetically identical at the DNA sequence level (but may show differences in gene expression due to, e.g., differences in DNA methylation levels; Jirtle & Skinner, 2007), any differences between two identical twins are due to nonshared environment.

Nonshared environmental influences are defined as environmental influences that make children growing up in the same family different and can include epigenetic processes, gene expression, illnesses, intra- and extrauterine environment, and measurement error. If de novo mutation events (e.g., rare de novo copy number variants, e.g., Sebat et al., 2007) or single nucleotide variants (Neale et al., 2012; O’Roak et al., 2012; Sanders et al., 2012) which have been linked to autism took place after the MZ twins separated, thus inducing differences between the twins, these effects will also be included in the nonshared environmental component. As such interpretations of nonshared environmental effects should always be considered in light of this definition.

A handful of studies have used structural MRI methods to report brain differences between MZ twins discordant for a narrow definition of autism.¹ Fourteen MZ pairs, nine of whom were clinically discordant for strictly defined autism, were examined and some neuroanatomical differences associated with this discordance (such as cerebellar volume) were reported. There was however also strong concordance across these pairs, for example, in cerebral gray and white volumes (Kates et al., 2004). Recently specific brain regions including the prefrontal cortex, amygdala, and hippocampus were examined, again finding that the degree of within-pair neuroanatomical concordance varied by brain region (Mitchell et al., 2009). The same sample has also been used to explore gyrification (cortical folding) patterns (Kates, Ikuta, & Burnette, 2009). Further research that attempts to replicate these interesting findings is needed.

One of the most well-replicated associations, in terms of putative risk factors, is between ASD and perinatal obstetric complications (Kolevzon, Gross, & Reichenberg, 2007; Ronald, Happé, Dworzynski, Bolton, & Plomin, 2010). Perinatal obstetric complications could be a result of preexisting genetic abnormalities in individuals who later develop ASD, could be a causal environmental risk factor, or could be both. To address whether perinatal obstetric complications could be an environmental risk factor for autistic traits, MZ twins in the UK-based TEDS sample who were discordant for postnatal birth complications (e.g., one twin had been in intensive care, the other had not) were compared on their later autistic trait scores. In some cases, significant correlations were observed between the two “difference” scores, that is, the twin with more postnatal birth complications had more autistic traits at a later age compared to their co-twin (Ronald, Happé, et al., 2010). In the Swedish CATSS sample, a co-twin control design was used to show that birth weight was modestly associated with autistic traits and risk of ASDs (Losh, Esserman, Anckarsäter, Sullivan, & Lichtenstein, 2012). These findings do not rule out that some birth weight and postnatal birth complications associated with autism or autistic traits could be due to genetic factors, but, if replicated, suggest that birth weight and postnatal complications can have a causative influence on a child’s later autistic traits and risk of ASD, above and beyond the influence of a child’s DNA code. This would fit with the predictions from twin studies, which consistently find evidence for nonshared environmental effects on autism and autistic traits.

Finally, a sample of three MZ pairs discordant for ASD diagnoses (one twin in each pair had autism; the other had some autistic traits and was described as “not quite autistic” or “broad spectrum”) has been studied in relation to their gene expression profiles (Hu, Frank, Heine, Lee, & Quackenbush, 2006; Sarachana, Zhou, Chen, Manji, & Hu, 2010) and their methylation profiles (Nguyen, Rauch, Pfeifer, & Hu, 2010). Both gene expression and epigenetic changes can occur as a result of genetic or environmental influences. The combination of phenotypically discordant genetically identical MZ twins and gene expression or epigenetic profiling allows for the discovery of biological mechanisms underlying nonshared environmental influences on autism (because DNA code is controlled for in the MZ differences design). Because MZ twins discordant for ASD are relatively rare, an inherent challenge of these MZ differences studies is how to employ a sample that has more participants than measured variables. Two options are to collaborate by combining samples and to study autistic traits rather than diagnosed ASD (see, e.g., Ronald, Happé, et al., 2010). Nevertheless, this is a promising field for further research.