News, literature, and events in the ethical, social, and legal implications of psychiatric, neurologic, and behavioral genetics. 
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   No.7            September 2014


In the Literature 

Anticipate and Communicate: Ethical Management of Incidental and Secondary Findings in the Clinical, Research, and Direct-to-Consumer Contexts
By Christine Weiner
This critique of the recent Presidential Commission for the Study of Bioethics' report argues that a consensus has not been reached on the protocols needed to anticipate and communicate incidental findings in genomic population research. A protocol-by-protocol approach makes sense for both investigators and IRBs as the research community thinks through the implications of genomic research. 

Genetics and intelligence differences: five special findings.
By Robert Plomin & Ian J. Deary
This study highlights five genetic findings that are special to intelligence differences and that have important implications for its genetic architecture and for gene hunting expeditions. These five findings arose primarily from twin studies. They are being confirmed by the first new quantitative genetic technique in a centuryGenome-wide Complex Trait Analysis, which estimates genetic influence using genome-wide genotypes in large samples of unrelated individuals.

Common Genetic Variants Associated with Cognitive Performance Identified Using the Proxy-Phenotype Method
By Cornelius A. Rietveld, Tõnu Eskoc, & Gail Davies et al.
This article features a genome-wide association study of educational attainment in a large sample, which produced a set of 69 education-associated SNPs. Then using independent samples it measures the association of these SNPs with cognitive performance. Three SNPs are significantly associated with cognitive performance after correction for multiple hypothesis testing. 

Uncovering the Hidden Risk Architecture of the Schizophrenias: Confirmation in Three Independent Genome-Wide Association Studies
By Javier Arnedo,  Dragan M. Svrakic, & Coral del Val et al.
In a large genome-wide association study of cases, the authors of this paper found that schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes. 

Gene×Environment Interactions in Early Externalizing Behaviors: Parental Emotional Support and Socioeconomic Context as Moderators of Genetic Influences?
By Amanda K. Cheung, Kathryn Paige Harden, & Elliot M. Tucker-Drob
This study uses two longitudinal population-based samples of young siblings to examine the effects of two hypothesized moderators of early externalizing behaviors: parental emotional support and family socioeconomic status. Results suggest that strong, positively correlated contextual factors may alter different genetic influences on distinct externalizing behaviors. 

Candidate Genes for Aggression and Antisocial Behavior: A Meta-analysis of Association Studies of the 5HTTLPR and MAOA-uVNTR
By Courtney A. Ficks & Irwin D. Waldman
A meta-analysis of associations of two genes, 5HTTLPR and MAOA-uVNTR, with aggression and antisocial behavior was conducted to determine: (1) the overall magnitude of effects for each polymorphism, (2) the extent of heterogeneity in effect sizes across studies and the likelihood of publication bias, and (3) whether sample-level or study-level characteristics could explain observed heterogeneity across studies. 

Problems and Pit-Falls in Testing for G×E and Epistasis in Candidate Gene Studies of Human Behavior
By Lindon Eaves & Brad Verhulst
Conclusions about the genetic architecture of a phenotype relating to the contributions of genetic dominance, epistasis, or genotype × environment interaction, depend upon the statistical and distributional properties of the measured trait. This dependence is frequently ignored in contemporary genetic studies and can radically change the conclusions that may be drawn from the data. 

Genotype-Environment Correlation in the Era of DNA
By Robert Plomin
An important implication of genotype-environment correlation is its shift from a passive model of the environment imposed on individuals to an active model in which individuals actively create their own experiences in part on the basis of their genetic propensities.

Interactive Effects of the COMT Gene and Training on 
Individual Differences in Supervisory Control of Unmanned Vehicles

By Raja Parasuraman et al.
Methods are needed for selection and training of human operators who can effectively supervise multiple unmanned vehicles (UVs). This study examined whether a gene known to influence dopamine availability in the prefrontal cortex is associated with individual differences in learning a supervisory control task. Individuals with the COMT Met/Met genotype can acquire skill in executive function tasks, such as multi-UV supervisory control, to a higher level and/or faster than other genotype groups.

Seminar on Ethical, Legal and Social Implications of Genetics

"Some Nice Parting Gifts: Why Current Human Biological Research Governance Is both Unsustainable and Undesirable"

Misha Angrist, PhD
Wednesday, October 1, 2014  4-5pm
Rm 405A and B, Educational Center, Irving Institute for Clinical and Translational Research
10th Floor, Presbyterian Hospital (PH) Building
622 W. 168th Street

To contribute a news item, an academic article, or an event on the ethical, legal, and social implications of psychiatric, neurological, and behavioral genetics research please email us.

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On July 31, the FDA announced it was considering expanding its mandate to regulate laboratory developed tests (LDTs).  Wendy Chung argues that such a plan would be “an unprecedented bureaucratic expansion” that “will reduce access to life-saving tests.” In reply, Rachel Sachs argues that the proposal would enable the FDA to collect much needed clinical utility data on tens of thousands of LDTs, which in turn “could improve patient care,” and that the carve outs in the proposed regulation would protect rather than stifle innovation.

In the News

‘Smart Genes’ Prove Elusive
 Study of more than 100,000 people finds three genetic variants for IQ, but their effects are minuscule. Experts admit that a study of more than 1 million people will be needed to confidently identify even a small genetic influence on intelligence and other behavioral traits.

Brain Genetics Paper Retracted
A study that identified genes linked to communication between different areas of the brain has been retracted by its authors because of statistical flaws. 

Mice Become Smarter With Addition of Single Human Gene
Researchers spliced a human brain gene into lab mice, and it made them smarter. Mice genetically modified to carry a human gene associated with speech and language, called Foxp2, learned how to find a reward in a maze significantly faster than normal mice. These findings reveal clues about how this particular gene contributes to humans’ unique intellectual abilities.

The Ethics of How to Manage Incidental Findings 
As advanced medical technologies have been increasingly applied in research and clinical care, researchers and clinicians should anticipate and plan for incidental findings. Acting on findings discovered incidentally during clinical tests or imaging for research purposes can have beneficial or harmful consequences for patients.

Multitasking Gene May Help Drone Operators Control Robotic Swarms
A genetic variant that keeps dopamine levels high could lead to personalized training and also benefit personnel in ERs and air traffic control towers.


The Stupidity of the “Smart Gene”
This commentary from the Center for Genetics and Society uses the "smart gene" as an example of the problems that come from overemphasizing the effect of individual genes on large, sweeping behavioral outcomes. 

Life Is Random
This article from Slate discusses how biologists now realize that “nature vs. nurture” misses the importance of random noise. The result is that two genetically identical cells in the same environment will sometimes behave in dramatically different ways.

Misbehaving Science

In Misbehaving Science, Aaron Panofsky traces the field of behavior genetics back to its origins in the 1950s, telling the story through close looks at five major controversies. In the process, Panofsky argues that persistent, ungovernable controversy in behavior genetics is due to the "archipelagic" structure of the field. 

Book Review

By Jonathan Anomaly
Anomaly discusses the tension between our responsibility as academics and as citizens in reviewing A Troublesome Inheritance by Nicholas Wade. 

In the Literature 

Rare Copy Number Variation in Treatment-Resistant Major Depressive Disorder
By Colm O’Dushlaine et al.
While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so this study assessed their association with treatment-resistant depression (TRD). It concluded that the contribution of rare CNVs to TRD appears to be modest, individually or in aggregate.

Genetic Studies of Major Depressive Disorder: Why Are There No Genome-Wide Association Study Findings and What Can We Do About It?
By Douglas F. Levinson et al.
This commentary examines why progress has been so difficult in gathering insights into the biological pathways involved in disease susceptibility for major depressive disorder through the genome-wide association study method, which has yielded significant insights into pathways for both schizophrenia and bipolar disorder. 

Humanized Foxp2 Accelerates Learning by Enhancing Transitions from Declarative to Procedural Performance
By Christiane Schreiweis, Ulrich Bornschein, & Eric Burguière et al. 
The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. When two substitutions of the endogenous gene related to language acquisition in humans are introduced to mice, learning and striatal neuroplasticity are affected. 
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