Our findings indicated that AFD is not specifically associated with alcoholism but rather is correlated with a broad range of indicators of disinhibited behavior and psychopathology. Moreover, individuals who first drink at a relatively early age manifest elevated rates of disinhibitory behavior and psychopathology before they first try alcohol. Taken together, these findings suggest that the association of AFD with alcoholism reflects, at least in part, a common underlying vulnerability to disinhibitory behavior. Whether an early AFD directly influences risk of adult alcoholism remains unclear.

Previous reviews of the literature have suggested that shared environmental effects may be underestimated in adoption studies because adopted individuals are exposed to a restricted range of family environments. A sample of 409 adoptive and 208 non-adoptive families from the Sibling Interaction and Behavior Study (SIBS) was used to identify the environmental dimensions on which adoptive families show greatest restriction and to determine the effect of this restriction on estimates of the adoptive sibling correlation. Relative to non-adoptive families, adoptive families experienced a 41% reduction of variance in parent disinhibitory psychopathology and an 18% reduction of variance in socioeconomic status (SES). There was limited evidence for range restriction in exposure to bad peer models, parent depression, or family climate. However, restriction in range in parent disinhibitory psychopathology and family SES had no effect on adoptive-sibling correlations for delinquency, drug use, and IQ. These data support the use of adoption studies to obtain direct estimates of the importance of shared environmental effects on psychological development.

Our findings indicated that AFD is not specifically associated with alcoholism but rather is correlated with a broad range of indicators of disinhibited behavior and psychopathology. Moreover, individuals who first drink at a relatively early age manifest elevated rates of disinhibitory behavior and psychopathology before they first try alcohol. Taken together, these findings suggest that the association of AFD with alcoholism reflects, at least in part, a common underlying vulnerability to disinhibitory behavior. Whether an early AFD directly influences risk of adult alcoholism remains unclear.

A detailed understanding of the genome-wide variability of single-nucleotide germline mutation rates is essential to studying human genome evolution. Here, we use ~36 million singleton variants from 3560 whole-genome sequences to infer fine-scale patterns of mutation rate heterogeneity. Mutability is jointly affected by adjacent nucleotide context and diverse genomic features of the surrounding region, including histone modifications, replication timing, and recombination rate, sometimes suggesting specific mutagenic mechanisms. Remarkably, GC content, DNase hypersensitivity, CpG islands, and H3K36 trimethylation are associated with both increased and decreased mutation rates depending on nucleotide context. We validate these estimated effects in an independent dataset of ~46,000 de novo mutations, and confirm our estimates are more accurate than previously published results based on ancestrally older variants without considering genomic features. Our results thus provide the most refined portrait to date of the factors contributing to genome-wide variability of the human germline mutation rate.

T he Enrichment Study (ES) was designed to extend the Minnesota Twin Family Study (MTFS)by oversampling 11-year-old twins at especially high risk for substance use disorders by virtue of having a childhood disruptive disorder. The sample was ascertained from Minnesota birth records. To identify high-risk twins, we conducted telephone screening interviews for parent-reported symptoms of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as well as indications of academic disengagement. Twins who exceeded a predetermined threshold were invited to participate. To facilitate comparison with the previously ascertained MTFS participants, a random sample of 11-year-old twins was also recruited. As part of the ES study, 499 twin pairs, and their parents, visited the University of Minnesota, where each participant completed a clinical interview, psychophysiological evaluation, and thorough assessment of environmental risk. We were highly successful in recruiting at-risk twins; 52% of the screened male twins and 41% of the screened females met criteria for a diagnosis of ADHD, CD, or oppositional defiant disorder (ODD). At the pair level, 63% of the screened pairs had at least one member with a childhood disruptive disorder. This article provides an overview of the study design and includes a review of recent findings using this sample of twins.