Objective To elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (< 13 years) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46×10-6 and 2.66×10-6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and improve statistical power for identifying genetic variants.

BackgroundThe Prevalence and persistence of ADHD have not been described in young Australian adults and few studies have examined how conduct problems (CP) are associated with ADHD for this age group. We estimate lifetime and adult prevalence and persistence rates for three categories of ADHD for 3795 Australian adults, and indicate how career, health and childhood risk factors differ for people with ADHD symptoms and ADHD symptoms plus CP.MethodologyTrained interviewers collected participant experience of ADHD, CP, education, employment, childhood experience, relationship and health variables. Three diagnostic definitions of ADHD used were (i) full DSM-IV criteria; (ii) excluding the age 7 onset criterion (no age criterion); (iii) participant experienced difficulties due to ADHD symptoms (problem symptoms).ResultsPrevalence rates in adulthood were 1.1%, 2.3% and 2.7% for each categorization respectively. Persistence of ADHD from childhood averaged across gender was 55.3% for full criteria, 50.3% with no age criterion and 40.2% for problem symptoms. ADHD symptoms were associated with parental conflict, poor health, being sexually assaulted during childhood, lower education, income loss and higher unemployment. The lifetime prevalence of conduct problems for adults with ADHD was 57.8% and 6.9% for adults without ADHD. The greatest disadvantage was experienced by participants with ADHD plus CP.ConclusionThe persistence of ADHD into adulthood was greatest for participants meeting full diagnostic criteria and inattention was associated with the greatest loss of income and disadvantage. The disadvantage associated with conduct problems differed in severity and was relevant for a high proportion of adults with ADHD. Women but not men with ADHD reported more childhood adversity, possibly indicating varied etiology and treatment needs. The impact and treatment needs of adults with ADHD and CP and the report of sexual assault during childhood by women and men with ADHD also deserve further study.

Background Substance use disorder (SUD) remains a significant public health issue. A greater understanding of how genes and environment interact to regulate phenotypes comprising SUD will facilitate directed treatments and prevention. Methods The literature studying the neurobiological correlates of SUD with a focus on the genetic and environmental influences underlying these mechanisms was reviewed. Results from twin/family, human genetic association, gene-environment interaction, epigenetic literature, phenome-wide association studies are summarized for alcohol, nicotine, cannabinoids, cocaine, and opioids. Results There are substantial genetic influences on SUD that are expected to influence multiple neurotransmission pathways, and these influences are particularly important within the dopaminergic system. Genetic influences involved in other aspects of SUD etiology including drug processing and metabolism are also identified. Studies of gene-environment interaction emphasize the importance of environmental context in SUD. Epigenetic studies indicate drug-specific changes in gene expression as well as differences in gene expression related to the use of multiple substances. Further, gene expression is expected to differ by stage of SUD such as substance initiation versus chronic substance use. While a substantial literature has developed for alcohol and nicotine use disorders, there is comparatively less information for other commonly abused substances. Conclusions A better understanding of genetically-mediated mechanisms involved in the neurobiology of SUD provides increased opportunity to develop behavioral and biologically based treatment and prevention of SUD.

Twin children from Australia, Scandinavia and the USA were assessed for inattention, hyperactivityimpulsivity and reading across the first three school years. Univariate behavior-genetic analyses indicated substantial heritability for all three variables in all years. Longitudinal analyses showed one genetic source operating across the time span and a second entering in the second school year for each variable, though possibly not reliable for inattention. Other analyses confirmed previous findings of pleiotropy (shared genes) between inattention and reading, and showed that this genetic overlap is in place from kindergarten onwards and is restricted to one of the genetic sources that affect reading and inattention. The results extend previous conclusions about the developmental trajectories of inattention, hyperactivity-impulsivity, and reading and their relationships. Limitations of this studyare discussed, as are educational implications.We are conducting a longitudinal twin study of early literacy, language, and aspects of behavior to identify genetic and environmental influences on these processes, on their developmental trajectories, and on their interactions. Data come from monozygotic (MZ) and dizygotic (DZ) twin pairs in Australia, Norway, Sweden and the United States starting in the children's final preschool year and continuing through kindergarten, Grade 1 and Grade 2. We refer to the project as the International Longitudinal Twin Study (ILTS). The focus of the current paper is the behavioral measures of attention and hyperactivity-impulsivity, treated as continuous variables rather than as clinical categories. The questions that we address are (1) the genetic and environmental influences on these constructs in each of the first three school years, (2) Correspondence concerning this article should be addressed to Jane L. Ebejer, School of Behavioral, Cognitive and Social Sciences, University of New England, Armidale, Australia 2351. jebejer@une.edu.au or Erik G. Willcutt, Department of Psychology, University of Colorado, Boulder, Colorado 80309. Erik.Willcutt@Colorado.edu. NIH Public Access Author ManuscriptSci Stud Read. Author manuscript; available in PMC 2011 July 1. Published in final edited form as:Sci Stud Read. 2010 July ; 14(4): 293-316. doi:10.1080/10888430903150642. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript developmental change and continuity in them across this time span, and (3) the relationship between these constructs and early reading. Relevant Findings from the ILTSAt the preschool level, we have shown that the composite measures of phonological awareness, rapid naming, and verbal memory that we developed are each subject to substantial genetic influence (Byrne et al., 2002;Samuelsson et al., 2005), and so are measures of inattention and hyperactivity-impulsivity derived from parent endorsements of ADHD symptoms . Print knowledge, vocabulary and grammar/morphology, in contrast, are more subject to influence from factors in twins' shared envir...