Context Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins. Objective To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment. Design, Setting, and Participants Twin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004were identified through the California Department of Developmental Services. Main Outcome Measures Structured diagnostic assessments (Autism Diagnostic Interview–Revised and Autism Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance rates were calculated and parametric models were fitted for 2 definitions, 1 narrow (strict autism) and 1 broad (ASD). Results For strict autism, probandwise concordance for male twins was 0.58 for 40 monozygotic pairs (95% confidence interval [CI], 0.42–0.74) and 0.21 for 31 dizygotic pairs (95% CI, 0.09–0.43); for female twins, the concordance was 0.60 for 7 monozygotic pairs (95% CI, 0.28–0.90) and 0.27 for 10 dizygotic pairs (95% CI, 0.09–0.69). For ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95% CI, 0.65–0.86) and 0.31 for 45 dizygotic pairs (95% CI, 0.16–0.46); for female twins, the concordance was 0.50 for 9 monozygotic pairs (95% CI, 0.16–0.84) and 0.36 for 13 dizygotic pairs (95% CI, 0.11–0.60). A large proportion of the variance in liability can be explained by shared environmental factors (55%; 95% CI, 9%–81% for autism and 58%; 95% CI, 30%–80% for ASD) in addition to moderate genetic heritability (37%; 95% CI, 8%–84% for autism and 38%; 95% CI, 14%–67% for ASD). Conclusion Susceptibility to ASD has moderate genetic heritability and a substantial shared twin environmental component.

We are performing whole genome sequencing (WGS) of families with Autism Spectrum Disorder (ASD) to build a resource, named MSSNG, to enable the sub-categorization of phenotypes and underlying genetic factors involved. Here, we report WGS of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible in a cloud platform, and through an internet portal with controlled access. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertion/deletions (indels) or copy number variations (CNVs) per ASD subject. We identified 18 new candidate ASD-risk genes such as MED13 and PHF3, and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (p=6×10−4). In 294/2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried CNV/chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.

The Vineland Adaptive Behavior Scales (2nd edition; Vineland-II) is the most widely used scale for assessing day-to-day "adaptive" skills. Yet, it is unknown how much Vineland-II scores must change for those changes to be regarded as clinically significant. We pooled data from over 9,000 individuals with ASD to show that changes of 2-3.75 points on the Vineland-II Composite score represent the "minimal clinically-important difference." These estimates will help evaluate the benefits of potential new treatments for ASD.

Introduction Multiple studies associate prenatal and perinatal complications with increased risks for autism spectrum disorders (ASDs). The objectives of this study were to utilize a twin study design to 1) Investigate whether shared gestational and perinatal factors increase concordance for ASDs in twins, 2) Determine whether individual neonatal factors are associated with the presence of ASDs in twins, and 3) Explore whether associated factors may influence males and females differently. Methods Data from medical records and parent response questionnaires from 194 twin pairs, in which at least one twin had an ASD, were analyzed. Results Shared factors including parental age, prenatal use of medications, uterine bleeding, and prematurity did not increase concordance risks for ASDs in twins. Among the individual factors, respiratory distress demonstrated the strongest association with increased risk for ASDs in the group as a whole (OR 2.11, 95% CI 1.27–3.51). Furthermore, respiratory distress (OR 2.29, 95% CI 1.12–4.67) and other markers of hypoxia (OR 1.99, 95% CI 1.04–3.80) were associated with increased risks for ASDs in males, while jaundice was associated with an increased risk for ASDs in females (OR 2.94, 95% CI 1.28–6.74). Conclusions Perinatal factors associated with respiratory distress and other markers of hypoxia appear to increase risk for autism in a subgroup of twins. Future studies examining potential gender differences and additional prenatal, perinatal and postnatal environmental factors are required for elucidating the etiology of ASDs and suggesting new methods for treatment and prevention.

OBJECTIVE: Patient registries can effectively collect data over a long period of time to provide a better understanding of the typical presentation of specific conditions. The autism spectrum disorders (ASDs) have experienced a marked increase in reported prevalence over the past 20 years for reasons that are not completely clear. The Autism Treatment Network (ATN) Registry was established to facilitate investigations into a variety of questions critical to expanding our understanding of ASDs. Here we describe the establishment of the registry, its components, some of its findings to date, and opportunities for further use of this data. METHODS:Participants are eligible for enrollment into the ATN registry if they are between the ages of 2.0 and 17.6 years at the time of enrollment and meet criteria for ASD as determined by clinical consensus on the basis of specific diagnostic measures (Autism