Tag: genome-wide association studies

Bioethics News

New Concerns Raised Over Value of Genome-Wide Disease Studies

June 21, 2017

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Compare the genomes of enough people with and without a disease, and genetic variants linked to the malady should pop out. So runs the philosophy behind genome-wide association studies (GWAS), which researchers have used for more than a decade to find genetic ties to diseases such as schizophrenia and rheumatoid arthritis. But a provocative analysis now calls the future of that strategy into question — and raises doubts about whether funders should pour more money into these experiments.

GWAS are fast expanding to encompass hundreds of thousands, even millions, of patients (see ‘The genome-wide tide’). But biologists are likely to find that larger studies turn up more and more genetic variants — or ‘hits’ — that have minuscule influences on disease, says Jonathan Pritchard, a geneticist at Stanford University in California. It seems likely, he argues, that common illnesses could be linked by GWAS to hundreds of thousands of DNA variants: potentially, to every single DNA region that happens to be active in a tissue involved in a disease.

In a paper published in Cell on 15 June1, Pritchard and two other geneticists suggest that many GWAS hits have no specific biological relevance to disease and wouldn’t serve as good drug targets. Rather, these ‘peripheral’ variants probably act through complex biochemical regulatory networks to influence the activity of a few ‘core’ genes that are more directly connected to an illness.

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Image via Flickr Attribution Some rights reserved by The Moonstone Archive

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The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

An Assessment of Mitochondrial Replacement Therapy

By: Alexa Woodward

Last year, a baby boy was born from an embryo that underwent mitochondrial replacement therapy (MRT). MRT was used to prevent this child from inheriting a mitochondrial disease from his mother, specifically infantile subacute necrotizing encephalomyelopathy – a disease that affects the central nervous system and usually results in death within the first few years of life. While controversial, assisted reproductive technologies (ARTs) such as MRT provide prospective parents with additional options and have the potential to improve the quality of human life by preventing disease.

This story is of bioethical interest because this technique results in germline modification, which is the alteration of DNA in the reproductive cells of humans that will be passed on to their offspring. Implementing MRT in humans has consequentially garnered much criticism, from simple health-related implications (such as unknown harms to potential offspring and eugenics concerns) to the futuristic next logical step of scientific intervention; directly editing the nuclear genome.

With MRT, modifications affect the mitochondrial genome (mtDNA), not the nuclear genome. Researchers emphasize the lack of bearing that mtDNA has on personal characteristics and the overall maintenance of “genetic integrity,” especially when compared to using the whole donor egg with an “unrelated” nuclear genome.1 Even so, additional concerns arise regarding the long-term anthropological effects, blurring the distinction between therapy and enhancement, and issues of resource allocation.

Mutations and deletions  in the mitochondrial genome can result in mitochondrial diseases affecting the neurological, musculoskeletal, cardiac, gastrointestinal, renal, and other systems, all of which are incurable.  MRT uses the intended parents’ nuclear DNA in conjunction with a donor’s mitochondria.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Research Ethics Roundup: Genome-Wide Association Studies Raise Diversity Concerns , India’s New Clinical Trial Guidelines, the European Medicines Agency’s Transparency Push, and Primate Research in the United Kingdom

This week’s Research Ethics Roundup examines new findings on who benefits from genome-wide association studies, India’s new informed consent provisions, the European Union’s new clinical study report policy, and British researchers’ arguments for non-human primate research.

The post Research Ethics Roundup: Genome-Wide Association Studies Raise Diversity Concerns , India’s New Clinical Trial Guidelines, the European Medicines Agency’s Transparency Push, and Primate Research in the United Kingdom appeared first on Ampersand.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

Solving the Lack of Diversity in Genomic Research

October 27, 2016

(MIT Technology Review) – A recent analysis published in the journal Nature revealed that 81 percent of participants in these genome-wide association studies were of European descent. Together, individuals of African, Latin American, and native or indigenous ancestry represent less than 4 percent of all genomic samples analyzed. While the overall diversity in genome-wide association studies has increased since 2009, when 96 percent of data was from people of European descent, much of the rise in diversity is due to large gains in Asian data and only marginal increases from other population groups.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Collaborative Science on Historically Burdened Concepts: Intelligence, Genetics, Race & Socio-economic Status

Image via Wikimedia: “Lithograph of a North American skull from Samuel Morton’s Crania Americana, 1839. Morton believed that intelligence was correlated with brain size and varied between racial groups”.

Charged Words

Intelligence is a highly charged word with ties to racist, classist, and eugenic narratives. In the United States, it has been used historically to assert and establish racial and class hierarchies, especially those between Blacks and Whites, and has long been linked to notions of biological difference.

In the early twentieth century, these notions were frequently explicit. As one example among many, Princeton psychologist Carl Campbell Brigham, creator of the SAT and member of the Advisory Council of the American Eugenics Society, wrote in 1922:

According to all evidence available…American intelligence is declining, and will proceed with an accelerating rate as the racial admixture becomes more and more extensive…There is no reason why legal steps should not be taken which would insure a continuously progressive upward evolution… The steps that should be taken to preserve or increase our present intellectual capacity must of course be dictated by science. (Brigham, 1922: 210)

Even in the years following World War Two, when overt claims of racial differences in intelligence were often muted, Nobel Laureate (in physics) William Shockley could openly argue:

I sincerely and thoughtfully believe that attempts to demonstrate that American Negro shortcomings are preponderantly hereditary is the action most likely to reduce Negro agony in the future… I propose a serious scientific effort to establish by how much the distribution of hereditary potential for intelligence of our black citizens falls below whites…If those Negroes with the fewest Caucasian genes are in fact the most prolific and also the least intelligent, then genetic enslavement will be the destiny of their next generation.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Cardiometabolic Disease: Big Data Tackles a Big Health Problem

More and more studies are popping up that demonstrate the power of Big Data analyses to get at the underlying molecular pathology of some of our most common diseases. A great example, which may have flown a bit under the radar during the summer holidays, involves cardiometabolic disease. It’s an umbrella term for common vascular and metabolic conditions, including hypertension, impaired glucose and lipid metabolism, excess belly fat, and inflammation. All of these components of cardiometabolic disease can increase a person’s risk for a heart attack or stroke.

In the study, an international research team tapped into the power of genomic data to develop clearer pictures of the complex biocircuitry in seven types of vascular and metabolic tissue known to be affected by cardiometabolic disease: the liver, the heart’s aortic root, visceral abdominal fat, subcutaneous fat, internal mammary artery, skeletal muscle, and blood. The researchers found that while some circuits might regulate the level of gene expression in just one tissue, that’s often not the case. In fact, the researchers’ computational models show that such genetic circuitry can be organized into super networks that work together to influence how multiple tissues carry out fundamental life processes, such as metabolizing glucose or regulating lipid levels. When these networks are perturbed, perhaps by things like inherited variants that affect gene expression, or environmental influences such as a high-carb diet, sedentary lifestyle, the aging process, or infectious disease, the researchers’ modeling work suggests that multiple tissues can be affected, resulting in chronic, systemic disorders including cardiometabolic disease.

The work, published in the journal Science and partially supported by NIH, was initiated by Johan L.M.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

International “Big Data” Study Offers Fresh Insights into T2D

Caption: This international “Big Data” study involved hundreds of researchers in 22 countries (red).

It’s estimated that about 10 percent of the world’s population either has type 2 diabetes (T2D) or will develop the disease during their lives [1]. Type 2 diabetes (formerly called “adult-onset”) happens when the body doesn’t produce or use insulin properly, causing glucose levels to rise. While diet and exercise are critical contributory factors to this potentially devastating disease, genetic factors are also important. In fact, over the last decade alone, studies have turned up more than 80 genetic regions that contribute to T2D risk, with much more still to be discovered.

Now, a major international effort, which includes work from my own NIH intramural research laboratory, has published new data that accelerate understanding of how a person’s genetic background contributes to T2D risk. The new study, reported in Nature and unprecedented in its investigative scale and scope, pulled together the largest-ever inventory of DNA sequence changes involved in T2D, and compared their distribution in people from around the world [2]. This “Big Data” strategy has already yielded important new insights into the biology underlying the disease, some of which may yield novel approaches to diabetes treatment and prevention.

The study, led by Michael Boehnke at the University of Michigan, Ann Arbor, Mark McCarthy at the University of Oxford, England, and David Altshuler, until recently at the Broad Institute, Cambridge, MA, involved more than 300 scientists in 22 countries.

The results from two related studies were combined to produce this work. One is called the Genetics of Type 2 Diabetes (GoT2D), which receives substantial NIH funding and included people from the United Kingdom, Sweden, Finland, and Germany.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Data Sharing in Clinical Trials: Webinar Follow-Up

By Samia Rizk, MD, professor of clinical pathology at Cairo University

Open data refers to “data that can be freely used, shared, and built-on by anyone, anywhere.” Data which is considered “open” is further required to be legally acceptable, technically readable, and available to others. The many potential benefits attributed to data sharing are combined with its many challenges: assuring privacy and security, the autonomy of participants as it relates to their ability to give valid consent, population and cultural issues, measures for appropriate governance, commercialization, and sustainability of databases.

With no binding requirement, it is a scientist’s decision whether or not to share data. Since transparency, openness, and reproducibility are considered part of the scientific method in research, data sharing aligns with those tenets.

In response to the need for a universal framework as to how, when, and what types of data should be shared, the Institute of Medicine’s Committee on Strategies for Responsible Sharing of Clinical Trial Data, recently reported guiding principles and a practical framework to implement data sharing across the research enterprise. To advance understanding of this issue, PRIM&R held a webinar titled, Maximizing Benefits to Research with Human Subjects Through Data Sharing, during which speakers discussed the Committee’s recommendations as they apply to those who review research with human subjects, and addressed data sharing in a research environment and the culture of data sharing at academic institutions.

Many initiatives for data sharing have been driven by funders and research sponsors in order to maximize the usefulness of data gathered.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Universal Newborn Genome Sequencing and Generation Alpha

I have been struggling with why the idea – and likely coming reality – of universal newborn genome sequencing disturbs me. It’s finally crystallized: the practice could create a genetic underclass.

On the day that genome sequencing of all newborns begins, a cohort of individuals about whom a tremendous amount of personal information exists will be instantly created. At the same time, the practice will establish a shrinking cohort of most of the rest of us who do not know our genome information.

A century from now, possibly everyone will have access to her or his genome data. But until then, how can we prepare to handle the avalanche of information of what I’d call, if I were a science fiction writer, “generation Alpha?”

My idea of the Alphas is inspired by the 1992 dystopian novel The Children of Men, by P.D. James. In 1994, all human sperm suddenly die, and 1995 becomes Year Omega. After that, populations plummet in the face of global infertility, with the last remaining people, the Omegas, struggling towards inevitable extinction.

What will happen in our world as the Alphas age? For now, mining sequenced genomes is experimental and seeks to end the “diagnostic odysseys” endured by patients, typically children with rare or one-of-a-kind diseases . But just as opening a magazine can reveal much more than the article one is looking for, a genome sequence provides hundreds of thousands of gene variants that might mean something about a person’s health. And so the American College of Medical Genetics and Genomics lists 56 “actionable” secondary (“incidental”) conditions, a minimal menu of conditions which doctors can prevent or treat.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Mining the Big Data Mountain

Cartoon of three men mining mountains of data

Credit: Chris Jones, NIH

Biomedical researchers and clinicians are generating an enormous, ever-expanding trove of digital data through DNA sequencing, biomedical imaging, and by replacing a patient’s medical chart with a lifelong electronic medical record. What can be done with all of this “Big Data”?

Besides being handy for patients and doctors, Big Data may provide priceless raw material for the next era of biomedical research. Today, I want to share an example of research that is leveraging the power of Big Data.

NIH-funded researcher Atul Butte of Stanford University recently mined mountains of existing data to find new links among genes, diseases, and traits. In this instance, traits are defined as any detectable physical or behavioral characteristic, such as cholesterol levels or other blood chemistries; bone density; or body weight. Butte reasoned that a trait that was closely linked to a disease through specific genes might be useful as a predictive marker of disease risk.

To discover these new links, he tapped into the VARiants Informing MEDicine (VARIMED) database, a resource that he began building in 2008 to interpret the clinical consequences of DNA variation in patients [1]. To create VARIMED, Butte and his colleagues read scientific papers on human genetics—including many genome-wide association studies (GWAS), which identify common genetic variants that are associated with disease risk—and noted the genes, variations, and traits mentioned in each paper and the connections between them. Over the years, the privately funded database grew; today it contains findings from more than 9,000 studies.

In their most recent study, Butte’s team examined the genetic architecture of each disease—all of the genetic variations that influence disease risk—and made a list of the gene-disease pairs.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.