Autistic disorder (OMIM 209850) is a disease with a significant genetic component of a complex nature. 1 Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (15q11-13) have been described in several individuals with autism. 1 For this reason, markers across this region have been screened for evidence of linkage and association, and a marker (155CA-2) in the ␥-aminobutyric acid type-A receptor 3 subunit gene (GABRB3) has been associated in one study 2 but not others. [3][4][5] We completed an association analysis with 155CA-2 using the transmission disequilibrium test (TDT) in a set of 80 autism families (59 multiplex and 21 trios). We also used four additional markers (69CA, 155CA-1, 85CA, and A55CA-1) localized within 150 kb of 155CA-2. The use of multi-allelic TDT (MTDT) (P < 0.002), as well as the TDT (P < 0.004), demonstrated an association between autistic disorder and 155CA-2 in these families. Meiotic segregation distortion could be excluded as a possible cause for these results since no disequilibrium was observed in unaffected siblings. These findings support a role for genetic variants within the GABA receptor gene complex in 15q11-13 in autistic disorder. Molecular Psychiatry ( Autism is a development disorder characterized by impairments in three domains: communication, reciprocal social interactions, and repetitive or stereotyped behaviors and interests (for review see TagerFlusberg et al 1 ). The concordance rate for monozygotic twins is much higher than that of dizygotic twins, which indicates that genetic factors play an important role in the etiology of autism. In addition, family studies indicate that the recurrence risk to siblings, estimated from multiple studies at 1-3%, is profoundly higher than the risk to the general population, which has been estimated at ෂ0.5-2 per 1000. The mode of inheritance of autism appears to be complex; latentclass analyses suggest that 3-10 genes may underlie the disorder, 6 although an interpretation of at least one genome-wide linkage analysis has argued for Ͼ10 genes underlying the disorder. 7 Cytogenetic studies have demonstrated that duplications within the 15q11-q13 region can be associated with autism (for review see Tager-Flusberg et al 1 ). Moreover, symptoms of autism can be associated with both Prader-Willi and Angelman syndromes, both of which involve alterations in the 15q11-q13 region. Because of this, the15q11-q13 region has been examined for genetic linkage to autism. A mapping of nine markers spanning a region of ෂ2 Mb within this region in 132 families demonstrated linkage disequilibrium at a marker within the GABRB3 gene, 155CA-2. 2 An additional locus within GABRB3 that is ෂ150 kb away from 155CA-2 (D15S97) did not demonstrate linkage disequilibrium.A genome-wide scan involving 51 autistic multiplex families demonstrated a broad peak with a LOD score of about 1 over the GABRB3 region. 8 Similarly, multipoint analyses over the region in 63 families demonstrated a peak Z-score of 1.78 in the region, near the marker ...
BackgroundThe emergence of dissemination and implementation (D&I) science has driven a rapid increase in studies of how new scientific discoveries are translated and developed into evidence-based programs and policies. However, D&I science has paid much less attention to what happens to programs once they have been implemented. Public health programs can only deliver benefits if they reach maturity and sustain activities over time. In order to achieve the full benefits of significant investment in public health research and program development, there must be an understanding of the factors that relate to sustainability to inform development of tools and trainings to support strategic long-term program sustainability. Tobacco control programs, specifically, vary in their abilities to support and sustain themselves over time. As of 2018, most states still do not meet the CDC-recommended level for funding their TC program, allowing tobacco use to remain the leading cause of preventable disease and death in the USA. The purpose of this study is to empirically develop, test, and disseminate training programs to improve the sustainability of evidence-based state tobacco control programs and thus, tobacco-related health outcomes.MethodsThis paper describes the methods of a group randomized, multi-phase study that evaluates the empirically developed “Program Sustainability Action Planning Training” and technical assistance in US state-level tobacco control programs. Phase 1 includes developing the sustainability action planning training curriculum and technical assistance protocol and developing measures to assess long-term program sustainability. Phase 2 includes a group randomized trial to test the effectiveness of the training and technical assistance in improving sustainability outcomes in 24 state tobacco control programs (12 intervention, 12 comparison). Phase 3 includes the active dissemination of final training curricula materials to a broader public health audience.DiscussionEmpirical evidence has established that program sustainability can improve through training and technical assistance; however, to our knowledge, no evidence-based sustainability training curriculum program exists. Therefore, systematic methods are needed to develop, test, and disseminate a training that improves the sustainability of evidence-based programs.Trial registrationNCT03598114. Registered 25 July 2018—retrospectively registered.
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