Monday, September 19, 2011

Twin spin

Autism spectrum disorder (ASD), while once considered to be induced by ‘bad’ parenting, is now considered a prototype complex genetic disorder on the basis of twin, family, and other genetic studies. Consistently, the heritable liability in ASD is estimated as between 80-90% (reviewed by Ronald & Hoekstra, 2011). However, not all ASD cases are inherited, and de novo (non-inherited or ‘sporadic’) mutations contribute to 5-20% of ASD cases (Marshall et al., 2008; Sebat J et al., 2007; Zhao X et al., 2007; Pinto et al., 2010; Levy D et al., 2011).  Factors such as parental age, multiple births, and foetal infection may increase the risk of de novo mutations (see Blog entry: Vaccination preventing autism).
            A recent twin study, which received a large amount of coverage in the popular press, has calculated a lower heritability estimate for ASD and a greater non-inherited contribution (Hallmayer J et al., 2011).  Hallmayer and colleagues (2011) therefore suggested that the non-inherited risk factors (environmental ‘triggers’) such as parental age, multiple births, and/or foetal infections, contribute to ASD aetiology.  Other perinatal risk factors for ASD have been suggested by recent data (see ARA Blog entry from Saturday, July 16, 2011), while previous studies highlighted a role for parental age and multiple births as factors increasing the risk of sporadic (rather than familial) ASD (Croen LA et al., 2002; Gardener H et al., 2009).
            However, the concordance data in the Hallmayer and coworkers study (2011) does not differ markedly from that of other ASD studies and, as a result, the methodology employed has been criticized by experts in the field (see SFARI comments at:  There is also concern that exclusion from their dataset of patients with some types of ASD may likewise affect their findings.
            This paper has been reviewed in detail on other blog sites:
            Therefore, while ASD is a prototypic complex genetic disorder, and the exact percentage contribution of non-heritable prenatal factors to selected ASD populations (compared to the contribution of heritable factors) varies, it also appears that these values can also vary depending on the statistical methods employed to analyze the data.

by Naomi Bishop

Key Reference:
Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen LA, Ozonoff S, Lajonchere C, Grether JK, Risch N.
Arch Gen Psychiatry 2011, Jul 4 [Epub ahead of print]

1 comment:

  1. Thanks for this Naomi. I saw your recent presentation at APAC and found it to be of great interest,
    kind regards