Teens’ Nuanced Views about Genetic Testing, at ESHG 2017

Posted by: Michael Dougherty, PhD, ASHG Director of Education

What do adolescents think about genetic testing – in particular, clinical recommendations to defer genetic testing for adult-onset conditions? We are beginning to have an answer, thanks to a research collaboration involving ASHG, Geisinger, and Sarah Lawrence College. Late last month, I had the opportunity to present our initial analysis at the 2017 European Human Genetics Conference (ESHG 2017) in Denmark.

Nyhavn waterfront, Copenhagen, Denmark. (Credit: Michael Dougherty)

First, for those who haven’t been to Copenhagen, it’s a beautiful city that I highly recommend. Deep history, friendly people (almost all of whom speak excellent English), and the convenient mass transit that is so typical of Europe. Walk along the canals or climb the external staircase to the top of Vor Frelser’s Kirke (Our Savior’s Church). An hour north of Copenhagen, Kronborg Castle, which is the model for Shakespeare’s Elsinore in Hamlet, is an especially nice day trip. If you’re adventurous, try the Danish national meal, ‘stegt flæsk,’ a delicious crispy pork dish, which came with the following warning in our restaurant’s menu: “Ask your waiter before ordering”! But now, back to the research.

Little is known about how adolescents view genetic testing, especially the psychosocial impacts of the benefits and harms frequently discussed by experts, yet clinical practice often involves decisions that may affect them. Our research used data from ASHG’s annual DNA Day Essay Contest entries to characterize adolescents’ views.

ASHG’s 2016 DNA Day Essay Contest question asked high school students to identify an adult-onset genetic condition and to defend or refute the recommendation in ASHG’s 2015 position statement to defer genetic testing until adulthood. Over 1,200 essays from 45 U.S. states and 22 non-U.S. countries were assessed using thematic, mixed-methods analysis. Students identified 100 conditions, but 75% chose one of five more familiar disorders, including Huntington disease, hereditary breast and ovarian cancer (e.g., BRCA), and Alzheimer’s. Across all conditions, roughly equal numbers of students chose to defer testing as to not defer.

We then dug deeper to examine students’ choices regarding specific conditions, such as testing for a BRCA predisposition to breast and ovarian cancer (BRCA) and for Alzheimer’s disease (AD), which differ considerably in medical actionability. Here some statistically significant differences began to emerge. With AD, nearly two-thirds of students chose to defer testing, whereas with BRCA, fewer than half chose to defer.

The reasons students gave to justify their decisions were sophisticated and often matched those reflected in clinical guidelines and ethical discussions. Reasons to defer often included risk of psychological harm to the minor or the uncertainty of predictions arising from test results (e.g., ApoE4). Reasons not to defer included the benefits of alleviating uncertainty and preparing for increased surveillance (e.g., early, regular mammograms).

The rich data provided in the students’ essays will be mined for additional insights that may inform the development of future recommendations, but even now it appears clear that the decisions of mature adolescents should be taken seriously by clinicians.

Michael J. Dougherty, PhD, is Director of Education at ASHG. This research collaboration’s work was presented at ESHG 2017 as a poster and featured in the meeting’s Best Posters Session.

Inside AJHG: A Chat with Eleazar Eskin

Posted by: Sara Cullinan, Deputy Editor, AJHG

Each month, the editors of The American Journal of Human Genetics interview an author of a recently published paper. This month, we checked in with Eleazar Eskin, PhD, former AJHG editorial board member and senior author of “Widespread Allelic Heterogeneity in Complex Traits”.

Eleazar Eskin, PhD
Eleazar Eskin, PhD, and recent ZarLab graduate Farhad Hormozdiari, PhD. (courtesy Dr. Eskin)

AJHG: How did you begin working on this project? 

Eleazar: This project originated when we observed a surprising result in a previous study, which was also published in AJHG. In our paper, “Colocalization of GWAS and eQTL Signals Detects Target Genes,” published in the December 2016 issue, we observed that for many loci which had both an observed expression quantitative loci (eQTL) signal as well as a GWAS signal, the actual variant responsible for these signals was different in the two studies. This was very surprising and was counter to the intuition of the field. We conjectured that what was going on was that many of the eQTL loci had multiple causal variants, referred to as allelic heterogeneity, and what could explain the observation is that the variants we are observing in the eQTL studies are only some of the variants affecting expression.

AJHG: What about this paper most excites you? 

Eleazar: The method that we developed can identify alleleic heterogeneity even when we can’t pinpoint the actual causal variants. We also showed that alleleic heterogeneity is very prevalent; the primary reason we haven’t been able to detect if more frequently is that our studies are under-powered.

AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?

Eleazar: Our study suggests that many variants are affecting each locus. Our result informs attempts to understand the mechanism underlying GWAS loci by providing a better understanding of how variants affect expression. In addition, this study helps us understand why we have, to date, been unable to detect colocalization of many GWAS and eQTL variants.

AJHG: What advice do you have for trainees/young scientists?

Eleazar: My main advice is to write up your research quickly. So much time is spent inefficiently in the writing process. On my lab website, zarlab.cs.ucla.edu, I have a series of blog posts with writing tips to help young scientists get their research published faster.

AJHG: And for fun, tell us something about your life outside of the lab.

Eleazar: I love to cook using traditional ethnic ingredients. I also love training for triathlons.

Eleazar Eskin, PhD, is a Professor of Computer Science and Human Genetics at UCLA. He has been a member of ASHG since 2006.


Reflecting on APHMG 2017

Posted by: Kathryn Garber, PhD, Chair of the ASHG Communications Committee

I’m just back from the annual meeting of the Association of Professors of Human and Medical Genetics (APHMG), and, as always, my head is swimming with ideas. For those not familiar with APHMG, it is a group that promotes human and medical genetics education in graduate and medical schools across North America. It’s a meeting where we spend most of our time talking about teaching and learning, but the fact that we are all geneticists means that we have a common understanding of the science we need to teach. We also discuss more practical issues of program design and oversight, particularly for medical students, residents and fellows.

APHMG 2017 attendees take a break from presentations for a pirate ship excursion. (courtesy Dr. Garber)

The focus of this year’s meeting was adult learning. Hope Ricciotti from Beth Israel Deaconess Hospital kicked things off with some valuable hints on interacting with millennial learners, including ideas on how to structure feedback to members of the “trophy generation”, who often aren’t used to negative feedback. Kadriye Lewis from Children’s Mercy Hospital in Kansas City then put adult learning in perspective through illustrations of different learning theories and their implementation. Next, Sarah Farrell and members of her team from Apple Education demonstrated tools and resources for use in education, including eBooks and courses that can be created or used by faculty, and apps that can foster interactivity in the classroom.

The second day of the meeting had a scientific focus on big data. Mike Murray from Geisinger described their approach to return of results to participants in their population-based GenomeFIRST project. He was followed by Sarah Elsea from Baylor, who discussed the use of large scale metabolomic profiles to identify inborn errors of metabolism. Finally, Piero Rinaldo from the Mayo Clinic argued passionately that we should stop using reference cutoffs to interpret biomarkers for metabolic disease, and should replace this approach with an assessment of the likelihood that an individual’s biomarker profile is more consistent with a normal or disease profile, based on large numbers of previously tested samples.

As usual, the annual meeting also included workshops by three special interest groups (SIGs), each one focused on a different set of trainees: medical genetics residents, medical students, and clinical laboratory fellows. I attended the medical student education workshop, which this year was co-sponsored by the Association of Biochemistry Educators (ABE). This allowed us to focus on topic integration across the undergraduate medical curriculum, and we had a productive small group session in which biochemists and geneticists worked together to develop teaching cases that integrate the two subjects. Later in the day, we brainstormed the inclusion of ethics in integrated medical curricula, as well as approaches to bringing the basic sciences into the clinical curriculum.

For me – and I think for many others – the most valuable part of the APHMG meeting is getting to know people who are teaching genetics at medical schools and hospitals across the country. We share ideas, create materials together, and establish collaborative projects that continue throughout the year. One of the key products of these interactions in recent years has been the sharing of resources that can be used broadly within the SIGs, including cases, assessments, evaluations, competency frameworks, and curricula. The Genetics Education Resource Exchange houses a number of these resources focused on undergraduate medical education. If your institution is an APHMG member, you can access this valuable resource. (Full disclosure: I was a member of the group that initiated this resource and was the founding curator of the resource exchange, a job that now belongs to Andrew Sobering from St. George’s University.)

If you want to meet and learn from people who are passionate about genetics education, this is the place, and I encourage you to join this supportive and collaborative group at our meeting in Santa Fe next spring. As you can see in the picture of our pirate ship excursion, we also make time for fun. Now, I’m off to take all of the great ideas that were sparked at the meeting and work on my syllabus for next semester.

Kate Garber, PhD, is an Associate Professor at Emory University. She is involved in designing and implementing human genetics training for physician assistants, genetic counselors, and medical students. Read more about Kate’s career.

How I Work: Brian Shirts

Posted By: Elisabeth Rosenthal, PhD, Member of the ASHG Communications Committee

We sat down with ASHG member Brian Shirts, MD, PhD, to learn more about his work at the cutting edge of clinical genetic diagnostics, including how his work intersects with his faith.

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Brian Shirts, MD, PhD. (courtesy Dr. Shirts)

ASHG: Tell us about your position and how it fits into your institution and its goals.

Brian: I am Assistant Professor of Laboratory Medicine at the University of Washington. Being in a clinical department means part of my job is doing clinical genetic testing in patients. Since I am at a university, the other part of my job is teaching and doing research. In order to have this position, I did medical school and doctoral training in human genetics. Then I did specialty training to be board certified in Clinical Pathology and Molecular Genetic Pathology. When I started graduate training, I did not know that the position I currently have existed. When I first met a physician who specialized in genetic diagnosis, I quickly realized, “That is what I wanted to do all along!”

Working at a university, I need to be on the cutting edge of clinical genetic diagnostics. I specialize in hereditary cancer testing and understanding the health effects of extremely rare genetic variants. When I say “extremely rare”, I mean genetic variants that I may see for the first time when I look at the results of a patient receiving clinical genetic testing, or a variant that may have only been seen in one or two other people in the world. In cancer risk genes, these variants are usually inherited and clustered in families, so I like to call them family-specific variants.

I am lucky because my research interests and my clinical work go well together. I spend over half of my time doing research and developing translational applications that will allow myself and others to apply my research discoveries to clinical diagnostics.

ASHG: How do you keep up with the latest in genetics science and use this in your work?

Brian: I try to attend the ASHG Annual Meeting and the Association for Molecular Pathology meeting as often as I can, as I think these are the best forums for the latest in genetics science and genetic diagnostics, respectively. I also read several journals and go to journal club presentations as often as I can.

ASHG: What are your favorite genetics websites?

Brian: I have to give a plug for my website on family studies for rare variant classification: findmyvariant.org. Some of my other favorite genetics websites for non-geneticists are: Genetics Home ReferenceLearn.Geneticsmy46, and Genetic Alliance.

ASHG: What are you currently reading/thinking about?

Brian: I am always thinking about how to apply population genetics principles to clinical diagnostics. For something completely different, I like to read the best books that my kids are reading. I am currently reading “Mr. and Mrs. Bunny–Detectives Extraordinaire!” by Polly Horvath.

ASHG: What everyday thing are you better at than everyone else? What’s your superpower?

Brian: When I go to church, others tell me that I have an extraordinary talent for asking appropriate yet thought provoking questions during Sunday School. Being an outspoken scientist in a faith community can be difficult to navigate, but communicating with people from different backgrounds is a really important skill to develop.

Brian Shirts, MD, PhD, is Assistant Professor of Laboratory Medicine at the University of Washington. He has been a member of ASHG since 2004.

Make Your ASHG 2017 Abstract Shine

Posted by: Emily Greene, MS, ASHG Meetings Program Coordinator

Watch our 2-minute video of tips to translate your great work into an equally great abstract.

ASHG 2017 abstracts are due in just a few weeks, and every year, abstract authors have the same question: How do I get my abstract programmed? The Rules & Policies and Step-by-Step Submission contain important information about how to conform to ASHG standards and avoid rejection, but today I’ll share some more nuanced tips to help abstract authors rise to the top of the pile.

Include the Most Relevant Information

First and foremost, write a clear, concise abstract that specifies what you did and why it’s exciting. If you sent your abstract to a friend in a distantly related genetics field, could he or she easily identify the work’s purpose, methods used, and key results? If not, then it’s back to the drawing board (or computer, in this case). You may think the information is self-evident, but abstract reviewers each read 150-200 of the >3000 abstracts submitted and will appreciate clarity – they are not mind readers!

Abstracts with broad scientific appeal and new information are more likely to be chosen for talks, especially for the Plenary Sessions. When asked their main reason for attending, most meeting attendees want “to hear about cutting-edge science.” Avoid using general language and clearly state what new information you will present, even if part of your work has been published. It is tempting to recycle language from old abstracts, but keeping your science fresh requires constant updating and a critical eye. Spending an extra hour on writing can reap big rewards if you are awarded a coveted speaking slot.

Remember: your abstract must report scientific findings. Abstracts are not the proper place to announce the availability of a new resource or service, or to advertise a particular product. Discussion of commercial products is permitted and colleagues from industry are encouraged to present, but remember to present objective information about those products, based on generally accepted scientific evidence. Presenting your work as “X product works better than Y product” is a sure way to score poorly during review.

Help Reviewers Classify Your Work

Once you have perfected your abstract and are ready to submit, you may be wondering which main topic and subtopic to select. In 2016, the topics were reorganized for the first time in many years. Authors now choose one main topic and one subtopic indicating what clinical phenotype, related trait, or biological system is being studied, rather than a single topic that might inaccurately describe the research. Of course, given the rise of interdisciplinary and collaborative studies, some authors will still struggle with this classification system. A good rule of thumb is to choose the topic and subtopic that are most appropriate for review. The number of talks chosen from each topic is scaled to the number of submissions, so your abstract has an equal chance of being chosen for a talk regardless of topic. Be sure to tag keywords in your abstract to help the reviewers and Program Committee identify exciting research and build themed sessions.

Follow these tips and submit by June 7, 2017 to have your work considered for ASHG 2017. Then, check out the overview of ASHG’s abstract review process and register to see all your colleagues’ impressive research.

Emily Greene, MS, is the Meetings Program Coordinator at ASHG. She works with the Program Committee and Meetings department to put together the scientific program for the ASHG Annual Meeting.

How I Work: Kathryn Garber

Posted by: Staff

We sat down with ASHG member Kathryn (Kate) Garber, PhD, to learn more about her unusual, three-part job and how she keeps up with it all (hint: superpowers are involved).

ASHG: Tell us about your position and how it fits into your institution and its goals.

Kathryn (Kate) Garber, PhD. (courtesy Dr. Garber)

Kate: I have three main pieces to my job: teaching, working in a clinical genetic testing lab, and writing for The American Journal of Human Genetics (AJHG). The typical tenure-track academic job wasn’t right for me, but I love academia, and I’ve managed to evolve my job into something that suits me and that fills a niche in our department. Emory has a medical school and training programs for physician assistants and genetic counselors, and all of these students are required to learn human genetics during their training. I have been involved in the design and implementation of each of these programs, and I teach in all three every semester. As I’ve gained more experience, I’ve also been involved in oversight of the medical school program, which has been a great learning opportunity for me.

In the clinical genetic testing lab, I am a variant analyst, which means that I classify DNA sequence variation as being pathogenic (disease-causing) or not before it is reported back to the ordering physician and patient. I also respond to clients who have questions about a variant classification and regularly discuss our classifications with other testing laboratories to help ensure consistency between labs. This job involves a lot of computer work and reading, and I’m constantly learning about new genes and new conditions. To me, it feels like solving puzzles, and I find it very interesting.

Finally, I write a monthly column called “This Month in Genetics” for AJHG. I scan the literature each month to find articles that I think will be of interest to the human genetics community, and then I write a short summary for each. Although sometimes it feels like the deadlines come faster and faster, I can’t think of a better opportunity to stay widely-read and to work on my writing skills. Some of my favorite days are spent scanning tables of contents looking for papers that catch my eye. Although translating that excitement into a few short sentences can be tricky, it is great practice for me in delivering complex information succinctly.

ASHG: How do you keep up with the latest in genetics science and use this in your work?

Kate: My work with AJHG really helps with that! But I also use GenomeWeb to monitor what’s going on. Attending seminars on a wide variety of topics is also something I find valuable, particularly for keeping up with techniques.

ASHG: What are your favorite genetics websites?

Kate: OMIM (Online Mendelian Inheritance in Man) and GeneReviews. Both are go-to websites for me on a daily basis. OMIM does such a great job summarizing the literature on disease genes and is a quick reference for inheritance patterns and to find the phenotype associated with a gene. GeneReviews is a great place to find overviews written by experts that summarize clinically relevant information for a variety of genetic conditions. Both are extremely valuable sources of information for the work that I do.

ASHG: What are you currently reading/thinking about?

Kate: Chromatin domains and other higher order ways to control genes. And because of some of my classes, I’ve been thinking a lot about the latest and greatest treatment strategies for genetic disease, such as RNA-based therapies and gene therapy.

An example of Kate’s PowerPoint pedigrees. (courtesy Dr. Garber)

ASHG: What everyday thing are you better at than everyone else? What’s your superpower?

Kate: It’s not a broadly applicable skill, but useful for a geneticist: drawing pedigrees in PowerPoint.

Kathryn (Kate) Garber, PhD, is an Associate Professor at Emory University and Chair of the ASHG Communications Committee. She has been a member of ASHG since 2007.

A New Policy Platform for ASHG

Posted by: Derek Scholes, PhD, ASHG Director of Science Policy

We are delighted to announce that ASHG has a new policy platform! Developed with the help of members and approved by the Board of Directors, the platform articulates where ASHG stands on a variety of policy issues – which issues are of key importance and our positions on those issues. It will provide direction for the Society’s policy and advocacy activities, and will be essential for communicating our policy perspectives to lawmakers and other stakeholders.

The platform covers four different policy categories that collectively capture the broad scope of ASHG’s policy interests. They are the conduct of genetics research, genetics in healthcare practice, societal uses of genetics, and the teaching of genetics and genetic literacy. Within each of these categories are highlighted a number of key issues, together with relevant statements that the Society has published. We define key issues as those that are consistent with our mission and where we can have an influential role.

Altogether, 17 key issues are listed. Of course, it will not be possible to address all of these at the same time. Rather, we’ll focus our energies according to the evolving policy environment and the prevailing needs of members. For example, in the past month, we’ve partnered with other societies within the Federation of American Societies for Experimental Biology to advocate for increased funding for biomedical research on Capitol Hill, especially timely given proposed cuts to NIH funding by the Trump Administration. We have also been drumming up opposition to the Preserving Employee Wellness Programs Act (H.R.1313), a bill introduced last month that would fundamentally undermine important provisions in the Genetic Information Nondiscrimination Act. Plus, we’ve been speaking out about the potential impact of proposed new travel restrictions to the U.S. on the international scientific community and the research enterprise.

In order to be successful in any of these advocacy activities, we need your help! To facilitate this, we have created a new Take Action page. Currently, you can visit the page to sign on to a letter opposing H.R.1313 and also let us know how the proposed immigration restrictions are impacting you. We’ll keep you updated as we continue to develop this.

Derek Scholes, PhD, is ASHG’s Director of Science Policy. For questions regarding ASHG’s policy and advocacy activities, email policy@ashg.org.