The Collaborative Study on the Genetics of Alcoholism: Overview.

Alcohol use disorders (AUD) are commonly occurring, heritable and polygenic disorders with etiological origins in the brain and the environment. To outline the causes and consequences of alcohol-related milestones, including AUD, and their related psychiatric comorbidities, the Collaborative Study on the Genetics of Alcoholism (COGA) was launched in 1989 with a gene-brain-behavior framework. COGA is a family based, diverse (~25% self-identified African American, ~52% female) sample, including data on 17,878 individuals, ages 7-97 years, in 2246 families of which a proportion are densely affected for AUD.

The collaborative study on the genetics of alcoholism: Brain function.

Alcohol use disorder (AUD) and related health conditions result from a complex interaction of genetic, neural and environmental factors, with differential impacts across the lifespan. From its inception, the Collaborative Study on the Genetics of Alcoholism (COGA) has focused on the importance of brain function as it relates to the risk and consequences of alcohol use and AUD, through the examination of noninvasively recorded brain electrical activity and neuropsychological tests. COGA's sophisticated neurophysiological and neuropsychological measures, together with rich longitudinal, multi-modal family data, have allowed us to disentangle brain-related risk and resilience factors from the consequences of prolonged and heavy alcohol use in the context of genomic and social-environmental influences over the lifespan.

Predicting Alcohol-Related Memory Problems in Older Adults: A Machine Learning Study with Multi-Domain Features.

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (the memory group) were compared with a matched control group who did not have memory problems.

Copy Number Variant Risk Scores Associated With Cognition, Psychopathology, and Brain Structure in Youths in the Philadelphia Neurodevelopmental Cohort.

Importance: Psychiatric and cognitive phenotypes have been associated with a range of specific, rare copy number variants (CNVs). Moreover, IQ is strongly associated with CNV risk scores that model the predicted risk of CNVs across the genome. But the utility of CNV risk scores for psychiatric phenotypes has been sparsely examined.

Stability of polygenic scores across discovery genome-wide association studies.

Polygenic scores (PGS) are commonly evaluated in terms of their predictive accuracy at the population level by the proportion of phenotypic variance they explain. To be useful for precision medicine applications, they also need to be evaluated at the individual level when phenotypes are not necessarily already known. We investigated the stability of PGS in European American (EUR) and African American (AFR)-ancestry individuals from the Philadelphia Neurodevelopmental Cohort and the Adolescent Brain Cognitive Development study using different discovery genome-wide association study (GWAS) results for post-traumatic stress disorder (PTSD), type 2 diabetes (T2D), and height.

What genes are differentially expressed in individuals with schizophrenia? A systematic review.

Schizophrenia is a severe, complex mental disorder characterized by a combination of positive symptoms, negative symptoms, and impaired cognitive function. Schizophrenia is highly heritable (~80%) with multifactorial etiology and complex polygenic genetic architecture. Despite the large number of genetic variants associated with schizophrenia, few causal variants have been established.

Genetic liability for substance use associated with medical comorbidities in electronic health records of African- and European-ancestry individuals.

Polygenic risk scores (PRS) represent an individual's summed genetic risk for a trait and can serve as biomarkers for disease. Less is known about the utility of PRS as a means to quantify genetic risk for substance use disorders (SUDs) than for many other traits. Nonetheless, the growth of large, electronic health record-based biobanks makes it possible to evaluate the association of SUD PRS with other traits.

Polygenic Risk of Psychiatric Disorders Exhibits Cross-trait Associations in Electronic Health Record Data From European Ancestry Individuals.

Background: Prediction of disease risk is a key component of precision medicine. Common traits such as psychiatric disorders have a complex polygenic architecture, making the identification of a single risk predictor difficult. Polygenic risk scores (PRSs) denoting the sum of an individual's genetic liability for a disorder are a promising biomarker for psychiatric disorders, but they require evaluation in a clinical setting.

Characteristics of youth with reported family history of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort.

Little is known about the impact of family history of psychosis on youth from community samples. To fill this gap, we compared youth with a first-degree relative with psychosis spectrum symptoms (i.e.

Harnessing Progress in Psychiatric Genetics to Advance Population Mental Health.

Advances in genomics and neuroscience have ushered in unprecedented opportunities to increase our understanding of the biological underpinnings of mental disorders, yet there has been limited progress in translating knowledge on genetic risk factors to reduce the burden of these conditions in the population. We describe the challenges and opportunities afforded by the growth of large-scale population health databases, progress in genomics, and collaborative efforts in epidemiology and neuroscience to develop informed population-wide interventions for mental disorders. Future progress is likely to benefit from the following efforts: expansion of large collaborative studies of mental disorders to include more systematically ascertained multiethnic samples from biobanks and registries, harmonization of phenotypic characterization in registry and population samples to extend clinical diagnosis to transdiagnostic concepts, systematic investigation of the influences of both specific and nonspecific environmental factors that may combine with genetic susceptibility to confer increased risk of specific mental disorders, and implementation of study designs that can inform gene-environment interactions.

Real-time Mobile Monitoring of the Dynamic Associations Among Motor Activity, Energy, Mood, and Sleep in Adults With Bipolar Disorder.

Importance: Biologic systems involved in the regulation of motor activity are intricately linked with other homeostatic systems such as sleep, feeding behavior, energy, and mood. Mobile monitoring technology (eg, actigraphy and ecological momentary assessment devices) allows the assessment of these multiple systems in real time. However, most clinical studies of mental disorders that use mobile devices have not focused on the dynamic associations between these systems.

Sex differences in estimated brain metabolism in relation to body growth through adolescence.

The human brain consumes a disproportionate amount of the body's overall metabolic resources, and evidence suggests that brain and body may compete for substrate during development. Using perfusion MRI from a large cross-sectional cohort, we examined developmental changes of MRI-derived estimates of brain metabolism, in relation to weight change. Nonlinear models demonstrated that, in childhood, changes in body weight were inversely related to developmental age-related changes in brain metabolism.

Parental Age and Offspring Psychopathology in the Philadelphia Neurodevelopmental Cohort.

Objective: Increasing evidence implicates advanced paternal age at offspring birth in neuropsychiatric disorders. Advanced maternal age has also been associated with schizophrenia and other neurodevelopmental disorders, whereas younger maternal age has been linked with behavioral disorders. Few studies have considered the specificity of the associations with respect to comorbidity.

Neurocognitive performance as an endophenotype for mood disorder subgroups.

Background: There is growing evidence that neurocognitive function may be an endophenotype for mood disorders. The goal of this study is to examine the specificity and familiality of neurocognitive functioning across the full range of mood disorder subgroups, including Bipolar I (BP-I), Bipolar II (BP-II), Major Depressive Disorders (MDD), and controls in a community-based family study.

Methods: A total of 310 participants from 137 families with mood spectrum disorders (n=151) and controls (n=159) completed the University of Pennsylvania's Computerized Neurocognitive Battery (CNB) that assessed the accuracy and speed of task performance across five domains.

The phenotypic manifestations of rare genic CNVs in autism spectrum disorder.

Significant evidence exists for the association between copy number variants (CNVs) and Autism Spectrum Disorder (ASD); however, most of this work has focused solely on the diagnosis of ASD. There is limited understanding of the impact of CNVs on the 'sub-phenotypes' of ASD. The objective of this paper is to evaluate associations between CNVs in differentially brain expressed (DBE) genes or genes previously implicated in ASD/intellectual disability (ASD/ID) and specific sub-phenotypes of ASD.

The phenotypic manifestations of rare CNVs in schizophrenia.

There is compelling evidence for the role of copy number variants (CNVs) in schizophrenia susceptibility, and it has been estimated that up to 2-3% of schizophrenia cases may carry rare CNVs. Despite evidence that these events are associated with an increased risk across categorical neurodevelopmental disorders, there is limited understanding of the impact of CNVs on the core features of disorders like schizophrenia. Our objective was to evaluate associations between rare CNVs in differentially brain expressed (BE) genes and the core features and clinical correlates of schizophrenia.

Summaries of oral sessions at the XXI World Congress of Psychiatric Genetics, Boston, Massachusetts, 17-21 October 2013: state of the field.

The XXI World Congress of Psychiatric Genetics (WCPG), sponsored by the International Society of Psychiatric Genetics (ISPG), took place in Boston, Massachusetts, on 17-21 October 2013. Approximately 900 participants gathered to discuss the latest findings in this rapidly advancing field. The following report was written by student travel awardees.

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk.

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants.