News, literature, and events in the ethical, social, and legal implications of psychiatric, neurologic, and behavioral genetics. 
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   Vol. 2, No. 2         March 2015


In the Literature

Ethical and Public Policy Challenges for Pharmacogenomics
By Elliot S. Gershon, Ney Alliey-Rodriguez, & Kay Grennan
Policy and ethical issues exist on consent for large-scale genomic pharmacogenomic data collection, public vs. corporate ownership of genomic research results, testing efficacy and safety of drugs used for rare genomic indications, and accessibility of treatments based on costly research that is applicable to relatively few patients. In major psychiatric disorders and intellectual deficiency, rare and de novo deletion or duplication of chromosomal segments (copy number variation), in the aggregate, are common causes of increased risk. This implies that the policy problems of pharmacogenomics will be particularly important for the psychiatric disorders.

Evaluating a Unique, Specialist Psychiatric Genetic Counseling Clinic: Uptake and Impact
By Angela Inglis et al.
The authors opened the first specialist psychiatric genetic counseling (GC) clinic of its kind, for individuals with non-syndromic psychiatric disorders and their families. Prior to GC and at a standard 1-month follow-up session, clinical assessment tools are completed, specifically, the GC outcomes scale (GCOS, which measures empowerment, completed by all clients) and the Illness Management Self Efficacy scale (IMSES, completed by those with mental illness). Mean GCOS and IMSES scores increased significantly after GC, indicating increases in empowerment and self-efficacy.

Genetic Investigation of Autism-Related Social Communication Deficits
By Daniel B. Campbell
Autism spectrum disorder includes a deficit in social communication as one of its underlying elements or endophenotypes. Endophenotypes are elements of a disorder that are thought to arise from a specific cause, usually a genetic variation. The chromosome 8 linkage loci identified in this study join five other genetic loci with genome-wide significant association to autism diagnosis. Two of these loci are also associated with quantitative social communication phenotypes in large general population samples, indicating that multiple genes contribute to autism-related endophenotypes. Researchers will need to look beyond the exome—the 2% of the human genome that encodes proteins—to identify genetic elements that contribute to autism spectrum disorder risk.

IQ and Schizophrenia in a Swedish National Sample: Their Causal Relationship and the Interaction of IQ With Genetic Risk
By Kenneth S. Kendler, Henrik Ohlsson, Jan Sundquist, & Kristina Sundquist
The authors sought to clarify the relationship between IQ and subsequent risk for schizophrenia. IQ was assessed at ages 18–20 in 1,204,983 Swedish males born between 1951 and 1975.
A robust interaction was seen between genetic liability to schizophrenia and IQ in predicting schizophrenia risk. Genetic susceptibility for schizophrenia had a much stronger impact on risk of illness for those with low than high intelligence. In this large, representative sample, there was no evidence for a link between genius and schizophrenia. Co-relative control analyses showed that the association between lower IQ and schizophrenia is not the result of shared familial risk factors and may be causal. High intelligence substantially attenuates the impact of genetic liability on the risk for schizophrenia.

Genetic and Environmental Influences on Obesity-Related Phenotypes in Chinese Twins Reared Apart and Together
By Bin Zhou et al.
The relative importance of genetic and environmental influences on obesity-related phenotypes remains unclear, and few studies have targeted the Chinese population. This study used Chinese twins reared apart and together to explore genetic and environmental influences on body mass index, waist circumference and waist–height ratio. Phenotype heritability was calculated using the structural equation model in 11,401 twin pairs aged 25–85 years. The correlated environment had a greater influence on the phenotypes than the rearing environment, especially on waist circumference and weight to height ratio, indicating that more correlated environment actions should be taken to prevent the rising trend of abdominal obesity.

FAAH Genetic Variation Enhances Fronto-Amygdala Function in Mouse and Human
By Iva Dincheva et al.
Cross-species studies enable rapid translational discovery and produce the broadest impact when both mechanism and phenotype are consistent across organisms. These researchers developed a knock-in mouse that biologically recapitulates a common human mutation in the gene for ​fatty acid amide hydrolase (​FAAH). This common polymorphism impacts the expression and activity of ​FAAH, thereby increasing ​anandamide (a neurotransmitter) levels. Here, the authors show that the mouse gene and human variant allele carriers exhibit parallel alterations in biochemistry, neuro-circuitry and behavior. These results suggest a gain in fear regulation and may indicate for which anxiety symptoms ​FAAH inhibitors or exposure-based therapies will be most efficacious, bridging an important translational gap between the mouse and human.

Fitting Procedures for Novel Gene-by-Measured Environment Interaction Models in Behavior Genetic Designs
By Hao Zheng & Paul J. Rathouz
For quantitative behavior genetic studies (e.g., twin), Purcell proposed a novel model for testing gene-by-measured environment (GxM) interactions while accounting for gene-by-environment correlation. Rathouz et al. expanded this model into a broader class of non-linear biometric models for quantifying and testing such interactions. This study proposes a novel factorization of the likelihood for this class of models, and adopts numerical integration techniques to achieve model estimation, especially for those without close-form likelihood. The new procedures are illustrated in a twin study analysis of the moderating effect of birth weight on the genetic influences on childhood anxiety. Both the extant GxM models and the new non-linear models critically assume normality of all structural components, which implies continuous, but not normal, manifest response variables.

In the News

Scientists Spot Gene Tied to Severe Autism in Girls
Researchers say they've discovered a new genetic cause of autism, singling out a rare gene mutation that appears to hamper normal brain development early on. The gene, CTNND2, provides instructions for making a protein called delta-catenin, which is crucial to the nervous system. The genomes of 13 girls with autism were sequenced and then compared to genes carried by people who did not have autism from a public database. The investigators detected four potential culprit genes for autism, including CTNND2.

Genetic Studies Yield New Insights into Obesity
Complex traits like obesity probably involve hundreds of low-volume genetic risk factors, each with a small effect that remains difficult to detect with our current techniques. Some genetic changes that promote obesity also elevate risk of high cholesterol, cardiovascular disease, and diabetes—but not equally so.

Your Genes Help Determine How Much Money You Save
A new paper connects data from the Swedish Twin Registry, a repository of information on fraternal and identical twins, to individual wealth data that the Swedish Tax Agency makes available to researchers. The researchers found that identical twins—who share the exact same genes—are significantly more similar in their savings behavior than fraternal twins. In fact, they conclude that genetic differences explained roughly 33% of the variations in individual savings rates.

Genetics of Altruism: Is Blood Really Thicker Than Water?
The outcome of a duel between mathematical models supports the reigning theory of the genetics of altruism. Called inclusive fitness, it says altruism is competitive if it benefits relatives carrying the same gene as the selfless individual.

Autism Detection Improved by Multimodal Neuroimaging
A new article published in Cortex is the first to combine three different measures of the brain — anatomy, the connectivity between different brain regions, and levels of a neurochemical — to distinguish people with autism spectrum disorder from matched, typically developing peers. This preliminary study needs to be validated with a larger sample, but it emphasizes that the brain abnormalities in autism may not be confined to a single area. Rather, they are distributed across different areas at multiple levels and layers.


One Brain Network for All Mental Illness
This blog post critiques a recent JAMA Psychiatry article by Goodkind et al. suggesting that a common neurobiological substrate may exist across mental illnesses. It argues that specific patterns of deficits in executive functioning for persons with mental illnesses differ depending on the psychiatric condition. It goes on to describe some of the different ways in which brain architecture operates and suggests a comprehensive review of imaging, genetic, and post-mortem neuroanatomical studies of brains from people who lived with schizophrenia, bipolar disorder, major depression, addiction, obsessive compulsive disorder, and anxiety. 

Informed Consent Literature

Enduring and Emerging Challenges of Informed Consent
By Christine Grady
Grady summarizes emerging standards for informed consent as the underpinning of ethical research in humans.

Customizing Informed Consent Procedures for People with Schizophrenia in India
By Sudipto Chatterjee et al.
There is little information on how the ethical and procedural challenges involved in the informed participation of people with schizophrenia in clinical trials are addressed in low- and middle-income countries (LMICs). The informed consent procedure used in the collaborative community care for people with schizophrenia in India (COPSI) was developed keeping these challenges in mind. The authors describe the feasibility of conducting the procedure from the trial, researcher and participants perspectives, and describe the reasons people consent or refuse to participate in the trial. The COPSI consent procedure demonstrates preliminary, observational information about the feasibility of customizing informed consent procedures for people with schizophrenia LMIC contexts.  

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