Evolving use of ancestry, ethnicity, and race in genetics research-A survey spanning seven decades.

To inform continuous and rigorous reflection about the description of human populations in genomics research, this study investigates the historical and contemporary use of the terms "ancestry," "ethnicity," "race," and other population labels in The American Journal of Human Genetics from 1949 to 2018. We characterize these terms' frequency of use and assess their odds of co-occurrence with a set of social and genetic topical terms. Throughout The Journal's 70-year history, "ancestry" and "ethnicity" have increased in use, appearing in 33% and 26% of articles in 2009-2018, while the use of "race" has decreased, occurring in 4% of articles in 2009-2018. Although its overall use has declined, the odds of "race" appearing in the presence of "ethnicity" has increased relative to the odds of occurring in its absence. Forms of population descriptors "Caucasian" and "Negro" have largely disappeared from The Journal (<1% of articles in 2009-2018). Conversely, the continental labels "African," "Asian," and "European" have increased in use and appear in 18%, 14%, and 42% of articles from 2009-2018, respectively. Decreasing uses of the terms "race," "Caucasian," and "Negro" are indicative of a transition away from the field's history of explicitly biological race science; at the same time, the increasing use of "ancestry," "ethnicity," and continental labels should serve to motivate ongoing reflection as the terminology used to describe genetic variation continues to evolve.

Human Genetics to Identify Therapeutic Targets for NAFLD: Challenges and Opportunities.

Non-alcoholic fatty liver disease (NAFLD) is a continuous progression of pathophysiologic stages that is challenging to diagnose due to its inherent heterogeneity and poor standardization across a wide variety of diagnostic measures. NAFLD is heritable, and several loci have been robustly associated with various stages of disease. In the past few years, larger genetic association studies using new methodology have identified novel genes associated with NAFLD, some of which have shown therapeutic promise. This mini-review provides an overview of the heterogeneity in NAFLD phenotypes and diagnostic methods, discusses genetic associations in relation to the specific stages for which they were identified, and offers a perspective on the design of future genetic mapping studies to accelerate therapeutic target identification.

2020 ASHG presidential address: the 'BIG TENT' of genetics/genomics and our world.

This article is based on the address given by the author at the 2020 virtual meeting of the American Society of Human Genetics (ASHG) on October 26, 2020. The video of the original address can be found at the ASHG website.

ASHG 2020 Curt Stern Award introduction: Fowzan Sami Alkuraya.

This article is based on the address given by the author at the 2020 virtual meeting of the American Society of Human Genetics (ASHG) on October 26, 2020. The video of the original address can be found at the ASHG website.

Assessing the Intention to Provide Human Genetic Resources: An Explanatory Model.

BACKGROUND: Human genetic resources are an important material component for life science research and have strategic significance for medical science and technological innovation. In this study, we employ frameworks from social psychology and the science of human behavior to study human genetic resource providers. AIMS: We used structural equation techniques to explain factors affecting the intention to provide human genetic resources and the mechanisms for providing such resources. METHODS: We conducted an online survey with respondents from ethnic minorities (n = 912). Our model integrates key variables informed by the theory of planned behavior (TPB), the theory of benefit and risk assessment (BRA), as well as variables that represent the policy and political system. RESULTS: Our results show that the factors affecting the intention to provide human genetic resources, ranked from highly influential to less influential, are perceived benefits, privacy risk, attitudes toward providing human genetic resources, perceived behavioral efficacy, psychological risk, subjective norms, and physical risk. The variables informed by the TPB all have a significant positive effect on the intention to provide human genetic resources. With the exception of physical risk, the variables informed by the theory of BRA have a significant effect on the intention to provide human genetic resources. Respondents with different health conditions have significantly different levels of physical risk. CONCLUSIONS: The results of our study provide insights into how to improve people's intention to provide human genetic resources. We also proposed ways to protect such resources globally.

Las ideas de Michael Sandel contra la visión transhumanista del perfeccionamiento de seres humanos / Las ideas de Michael Sandel contra la visión transhumanista del perfeccionamiento de seres humanos / Michael Sandel's ideas against transhumanist vision of the perfection of human beings / Michael Sandel's ideas against transhumanist vision of the perfection of human beings

Las tentadoras promesas del transhumanismo parecen estar cada vez más cerca, pero cabe preguntarse si no resultarán contraproducentes en algún sentido. El profesor Sandel expone los problemas sociales que conllevaría el desarrollo de seres humanos mejorados en nuestra concepción del mérito, la libertad y responsabilidad, el aprecio de la vida como un don, la inclinación a compartir nuestro destino con el de los demás y la concepción de los derechos individuales

Las tentadoras promesas del transhumanismo parecen estar cada vez más cerca, pero cabe preguntarse si no resultarán contraproducentes en algún sentido. El profesor Sandel expone los problemas sociales que conllevaría el desarrollo de seres humanos mejorados en nuestra concepción del mérito, la libertad y responsabilidad, el aprecio de la vida como un don, la inclinación a compartir nuestro destino con el de los demás y la concepción de los derechos individuales

The tempting promises of transhumanism seem to be getting closer and closer, but in some way counterproductive in some way. Professor Sandel presents the social problems that the development of improved human beings would entail in our understanding of merit, freedom and responsibility, the appreciation of life as a gift, the inclination to share our destiny with others and the conception of individual rights

The tempting promises of transhumanism seem to be getting closer and closer, but in some way counterproductive in some way. Professor Sandel presents the social problems that the development of improved human beings would entail in our understanding of merit, freedom and responsibility, the appreciation of life as a gift, the inclination to share our destiny with others and the conception of individual rights

The Ethics of Precision Rationing: Human Genetics and the Need for Debate on Stratifying Access to Medication.

Rising prices for new, transformative therapies are challenging health systems around the world, leading many payers and providers to begin rationing access to treatments, even in the countries that have been most resistant to doing so. This is the case for direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV). However, little attention has been paid to the increasing role that human genetics might play in rationing decisions. Researchers have already proposed that genetic markers associated with spontaneous HCV clearance could be used to restrict DAA access for some patients, although treatment would be medically beneficial for those patients. Would such forms of rationing present a form of genetic discrimination? And what of the public health implications of these approaches? Here we present an ethical analysis of such proposals for "precision rationing" and raise 4 key areas of concern. We argue that ethical issues arising in this area are not substantively different from the pressing ethical issues regarding rationing and discrimination more broadly, but provide important impetus for motivating broad public debate to find ethically sound ways of managing genomics and new expensive medications.

The SNP-Based Heritability - A Commentary on Yang et al. (2010).

I write this commentary as a part of a special issue published in this journal to celebrate Nick Martin's contribution to the field of human genetics. In this commentary, I briefly describe the background of the Yang et al. (2010) study and show some of the unpublished details of this study, its contribution to tackling the missing heritability problem and Nick's contribution to the work.

Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies.

Neuropsychiatric disorders are frequently complicated by aggressive behaviors. For some individuals, existing behavioral and psychopharmacological treatments are ineffective or confer significant side effects, necessitating development of new ways to treat patients with severe aggression. Nicotinic acetylcholine receptors (nAChRs) are a large and diverse family of ligand-gated ion channels expressed throughout the brain that influence behaviors highly relevant for neuropsychiatric disorders, including attention, mood, and impulsivity. Nicotine and other drugs targeting nAChRs can reduce aggression in animal models of offensive, defensive, and predatory aggression, as well as in human laboratory studies. Human genetic studies have suggested a relationship between the CHRNA7 gene encoding the alpha-7 nAChR and aggressive behavior, although these effects are heterogeneous and strongly influenced by genetic background and environment. Here we review animal, human genetic, and clinical studies supporting a consistent role of nicotine and nAChR signaling in modulation of aggressive behaviors. We integrate findings from recent studies of aggression neuroscience, discuss the circuitry that may be involved in these effects of nAChRs, and identify multiple key questions that must be answered prior to safe and effective translation for human patients. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.

Next-generation drug repurposing using human genetics and network biology.

Drug repurposing has attracted increased attention, especially in the context of drug discovery rates that remain too low despite a recent wave of approvals for biological therapeutics (e.g. gene therapy). These new biological entities-based treatments have high costs that are difficult to justify for small markets that include rare diseases. Drug repurposing, involving the identification of single or combinations of existing drugs based on human genetics data and network biology approaches represents a next-generation approach that has the potential to increase the speed of drug discovery at a lower cost. This Pharmacological Perspective reviews progress and perspectives in combining human genetics, especially genome-wide association studies, with network biology to drive drug repurposing for rare and common diseases with monogenic or polygenic etiologies. Also, highlighted here are important features of this next generation approach to drug repurposing, which can be combined with machine learning methods to meet the challenges of personalized medicine.

Asia Pacific Society of Human Genetics (APSHG) from conception to 2019: 13 years of collaboration to tackle congenital malformation and genetic disorders in Asia.

Putting together the reports in this issue that come from a representation of the different countries in Asia presents an opportunity to share the unique story of the Asia Pacific Society of Human Genetics (APSHG), which has provided the authors of many of these articles. This paper, authored by the Past Presidents of the Society, shares glimpses of how medical genetics activities were first organized in the Asia Pacific region and provides interesting corollaries on how under-developed and developing countries in this part of the world had developed a unique network for exchange and sharing of expertise and resources. Although APSHG was formally registered as a Society in Singapore in 2006, the Society has its origins as far back as in the 1990s with members from different countries meeting informally, exchanging ideas, and collaborating. This treatise documents the story of the experiences of the Society and hopes it will provide inspiration on how members of a genetics community can foster and build a thriving environment to promote this field.

The Future of Genomic Studies Must Be Globally Representative: Perspectives from PAGE.

The past decade has seen a technological revolution in human genetics that has empowered population-level investigations into genetic associations with phenotypes. Although these discoveries rely on genetic variation across individuals, association studies have overwhelmingly been performed in populations of European descent. In this review, we describe limitations faced by single-population studies and provide an overview of strategies to improve global representation in existing data sets and future human genomics research via diversity-focused, multiethnic studies. We highlight the successes of individual studies and meta-analysis consortia that have provided unique knowledge. Additionally, we outline the approach taken by the Population Architecture Using Genomics and Epidemiology (PAGE) study to develop best practices for performing genetic epidemiology in multiethnic contexts. Finally, we discuss how limiting investigations to single populations impairs findings in the clinical domain for both rare-variant identification and genetic risk prediction.

Spinning the Genome: Why Science Hype Matters.

There is a growing body of literature that describes both the degree to which science is hyped and how and why that hype happens. Hype can be described as an inappropriate exaggeration of the significance or potential value of a particular study or area of science. Evidence tells us that this spin happens throughout the science translation process. There is hype in research grants, peer-reviewed publications, scientific abstracts, institutional press releases, media representations, and, of course, in the associated marketing of a new product. There is also evidence that it has played a particularly significant role in the area of genetic research. Science hype is a complex phenomenon that involves many actors. And it is, at least to some degree, the result of systemic pressures imbedded in the current incentives associated with biomedical research. This article reviews what the evidence says about the sources of hype, the social and scientific harms, and what can be done to nudge us in the right direction.