Recap: ASHG-AJHG Webinar on Polygenic Risk Scores

Posted By: Ann Klinck, Communications & Marketing Assistant, ASHG

With growing interest in polygenic risk scores (PRS) and questions arising about its clinical relevance, ASHG and The American Journal of Human Genetics (AJHG) hosted the webinar The Development and Application of Polygenic Risk Scores. The archived video is now available for viewing.

Bruce Korf, AJHG editor and webinar moderator, was joined by Eimear Kenny, PhD, Director of the Center for Genomic Health at the Icahn School of Medicine at Mount Sinai, and Sekar Kathiresan, MD, Director of the Center for Genomic Medicine at Massachusetts General Hospital, and Director of the Cardiovascular Disease Initiative at the Broad Institute.

Origins of Polygenic Risk Scores

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Eimear Kenny, PhD (provided by Dr. Kenny)

With much research leading to the growth of PRS, Dr. Kenny believes the research paper The Correlation between Relatives on the Supposition of Mendelian Inheritance (1918) from R.A. Fisher was a huge contributor to the modern-day field complex trait genetics. Fisher defined the term variance, introduced the analysis of variance to partition observed variation into underlying casual factors, and theorized that several genes could contribute to variation using mendelian segmentation. This work led to understanding the genetic architecture and the prediction of complex traits.

 

Dr. Kenny went into further detail on the background of PRS, which you can see in the archived webinar (skip to 4:53).

What is a PRS? 

A PRS is defined as “a genetic prediction of an individuals’ phenotype. It is calculated by summing across the products of a genome-wide association study (GWAS) effect sizes and number of trait-increasing alleles.” Dr. Kenny said that the ultimate goal of a PRS is to predict the phenotype in an out of sample individual who does not have a recorded phenotype.

So, Where Does GWAS Fit In?

Dr. Kenny emphasized that the explosion of GWAS was a tipping point for risk prediction and has expanded in both number of studies and size. GWASs provide evidence supporting Fisher’s theory that most heritable variation is due to thousands of genetic variants each with a tiny marginal effect.

In other words, the genetic architecture of complex traits is almost always highly polygenic. Essentially, the expansion of PRS and GWAS go hand-in-hand.

Where is PRS Being Seen in the Field?

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Sekar Kathiresan, MD (courtesy Dr. Kathiresan)

PRS are influencing a variety of subject areas including epidemiology, statistics, public health, social science, and medicine. Dr. Kathiresan shared the real-world case of a 42-year-old male patient, who suffered a heart attack after being told six months prior that he had only a 1.7% chance of having a heart attack within the next ten years. In this case, other methods of predicting heart attack risk like cholesterol, triglycerides, or blood pressure were not helpful preventatives. As the current heart attack risk prediction model is largely driven by age, heart attack in people under 55 is difficult to predict.

“For early-onset disease, stratifying individuals based on inborn DNA variation is an important option, being as most diseases have an inherited component,” Dr. Kathiresan noted. What this could lead to is earlier interventions outside of lifestyle changes, like the use of a statin medication.

Essentially, over the last 15 years, it’s been found that using a polygenic risk model can identify other at-risk individuals. Dr. Kathiresan believes that in the next five years, polygenic risk will start to be incorporated when calculating a patient’s heart attack risk.

To hear more about the work on heart attack risk and other common complex diseases, check out the full webinar (skip to 35:02).

Representing the Global Population

Though there are millions of GWAS participants, most databases driving the GWAS and PRS research are of European ancestry, while only one-seventh of the world’s population has European ancestry. PRS can be adjusted for ancestry, but if based on current data, scores may not be as accurate for non-European populations.

Dr. Kenny described increasing diversity amongst genetic study participants as a multi-pronged issue (skip to 1:00:12). There are many efforts to recruit diverse populations, not only in ancestry, but in community type and socioeconomic status. Still, there is a lot of work to be done. Dr. Kenny believes that increasing diversity in the scientific community as a whole will allow labs to think about participant diversity more clearly.

Dr. Kathiresan agrees and pointed out that participant diversity is important for not only common disease genetics, but also for rare disease genetics in terms of who has been sequenced and the ability to then interpret rare variation.

Conclusions

PRS is a fast-moving area of interest but is just one developing approach to genomics and health, and there are many others such as transcriptional risk scores, epigenetics, and copy-number variation.

“I am optimistic about our ability as a field to really tackle these questions, problems, and challenges,” said Dr. Kenny in conclusion. “There are reasonable solutions, and we can pursue them. I’m hopeful we as a scientific community engage a lot more with the public, clinicians, and other stakeholders that think about these similar questions.”

Next Webinar:

Exploring the Responsibility to Recontact

Six Months in as an Education Fellow: My Experience So Far

Posted by: Dyanna Christopher, MPH, ASHG/NHGRI Genetics Education & Engagement Fellow

My first few months as a Genetics Education & Engagement Fellow, which have included rotations at the National Human Genome Research Institute (NHGRI) and ASHG, have been full of lessons, new experiences, and opportunities to increase my skill set.

2019-2020 Education Fellow
Dyanna Christopher, MPH, ASHG/NHGRI Genetics Education & Engagement Fellow (courtesy Ms. Christopher)

At NHGRI, I’ve learned more about government agencies and how they work. I’ve begun to develop partnerships across the National Institutes of Health (NIH) and the surrounding community, and have seen that the NIH is a collaborative environment, and how small the genetics community is in the DC area. At ASHG, I have discovered some of the roles of scientific societies and the importance of member relationships. I have seen the behind-the-scenes work required to build a community and plan valuable events. I’ve had the opportunity to participate in and even spearhead events helping to increase genetic understanding and health literacy in different communities.

My major project while at NHGRI was the NBC4 Health and Fitness Expo. This project required immense collaboration and preparation. Though weekend snow covered the streets of the district, we were still able to educate and engage over 200 community members and talk to them about genetic risk assessment, direct-to-consumer genetics, basic genetics and genomics, and some of the things that happen at NHGRI. Seeing the public converse about how genetic health history impacts their lives was a highlight for me. It’s so important to show those who may not have a vested interest in science how it impacts them and affects their day-to-day lives.

This was not my only project that focused on facilitating and increasing genetics education and engagement. Shortly after starting my rotation at ASHG, I was able to help find and develop tools for ASHG members that aid them in answering questions about genetics and genomics from nonscientific communities. ASHG is a trusted source for up-to-date genetics information and my hope is that members of ASHG can locate resources that help them answer and respond to public inquiries.

I have also had the opportunity to speak with budding scientists through an event organized by the Johns Hopkins Center for Talented Youth program. I served as a panelist and talked to gifted high school students about my career and educational experiences in the field. This event allowed me to speak on the importance of genetics, genomics, and health literacy, and to bring awareness to the importance of understanding these topics. It was great to see so many young people excited about science and the influx of different career options available to budding scientists. I’ve also had the opportunity to help increase diversity at NHGRI by helping to find and recruit committee members from diverse populations who have a vested interest in genetics and genomics.

The fellowship is just getting started. I know that there will be even more opportunities to learn, serve, and develop as a scientist and educator.

Interested in the intersection of genetics with education and public engagement? Consider applying for the ASHG/NHGRI Genetics Education & Engagement Fellowship!  Applications are open through April 19, 2019.

DNA Day on April 25: An Opportunity to Engage

Posted By: Ann Klinck, Communications and Marketing Assistant, ASHG

National DNA Day started in 2003 to commemorate the completion of the Human Genome Project and engage communities with science. Last month, ASHG hosted the webinar “Take Initiative: DNA Day Engagement and You,” which covered how to get involved, resources, and best practices.

Listeners were joined by moderator Maurice Godfrey, Incoming Chair of ASHG’s Information & Education Committee; Carla Easter, Chief of Education and Community Involvement at the National Human Genome Research Institute (NHGRI); and Christina Vallianatos, Founder and co-Director of Michigan DNA Day.

Importance of Science Engagement

Public engagement with science is imperative every day, but DNA Day provides the opportunity to make it a priority. Christina explained that her organization’s mission helps demystify science for students, and that “Many scientists’ careers aren’t linear. The simple act of awareness can help students know what other fields are out there in science outside of doctors and nurses.”

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Michigan DNA Day has grown tremendously in a short time, showing that not only is science engagement important, but people enjoy it! (courtesy Ms. Vallianatos)

Ways to Get Involved

The speakers outlined numerous ways and resources for involvement:

National Events: Carla described larger DNA Day-related events that NHGRI oversees. Students are able to visit the NIH Campus and go on lab tours, and NHGRI facilitates interactive programming with the Smithsonian Institute, a lecture, and a seminar series. Past events are listed online, and 2019 events should be available soon.

Maurice encouraged listeners to get involved in ASHG’s Annual DNA Day Essay Contest. This year’s contest addresses the disclosure of a genetic diagnosis to one’s family. Participating students can win cash prizes and funding for their science programs at school.

Local Events: Christina’s program is localized to Michigan, but many other states offer events like it. If your state does not have an organization in place, scientists could simply reach out to their local schools and offer to speak with them for one class period. Teachers should also not be hesitant to reach out to professors at local colleges. Christina said, “Keep it simple! If you just make one contact at one school, it was worth the effort, because it will have an impact.”

Resources & Best Practices

The speakers provided several resources, including:

An overarching theme was to make your interactions as hands-on as possible. Christina says that when engaging with students, it should be “less about teaching and more about the interaction with science.” If students are given something physical to do, it’s more likely to stick with them.

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Michigan DNA Day’s scientists out in a high school classroom.(courtesy Ms. Valliantos)

Similarly, Maurice kept activities hands-on and interactive when developing a DNA Day program for the Omaha Zoo and Aquarium’s “Key to Diversity in Animals and People Festival,” a larger event that lasted a whole weekend.

Want to get involved or find more resources? Email ASHG at dnaday@ashg.org, NHGRI at dnaday@nih.gov, or Michigan DNA Day at midnaday@gmail.com.

Submissions for the ASHG DNA Day Essay Contest are due March 8, 2019! If you’re a member of ASHG and interested in getting involved in science engagement, sign up for the Genetics Engagement & Education Network or contact education@ashg.org.

Announcing: The Genetics Engagement & Education Network

Posted by: Alexis Norris, PhD, Member of ASHG Information & Education Committee

I’m pleased to share that the ASHG Information & Education (I&E) Committee has revamped the previous Genetic Education Outreach Network (GEON) program as the Genetics Engagement & Education Network. The purpose of this program is to create a network for ASHG members to engage and educate. Members of the network will receive a quarterly newsletter, have access to a toolkit of educational resources vetted by the I&E Committee, and have their name added to the Network directory. The directory can be used by ASHG members to find speakers and collaborators, and by the public to connect with members about human genetics-related questions. Questions often range from visiting a classroom, to hosting a field trip, to offering academic and schooling advice.

In our world of wide-reaching, fast paced, and bite-sized communication, we are faced with communicating our science to many audiences, from fellow scientists in our field to the lay public. It is challenging to share information in a way that it is both approachable and understandable. Engaging in education outreach can improve your science communication, through the experience of deconstructing complex concepts into their digestible parts, and identifying what sparks the audience’s interest.

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Hands-on activities using real world examples, such as this one on identifying fish species using DNA sequences collected in Atlantic Ocean, help students understand genetics and genomics concepts. (courtesy Dr. Norris)

The toolkit and newsletter will also give members access to new ideas about how to communicate and educate. ASHG members can enroll in the Network through the ASHG portal indicating their geographical region and outreach audiences of interest (e.g., high school, college, or general public).

For teachers, inviting an ASHG member to their classroom has immediate and clear benefits for their students. First, the activity can be timed to coincide with genetics lessons, thus reinforcing concepts and their applications. The ASHG member also provides a tangible example of a career path in genetics, and a potential resource and networking connection for the students.

Why I Find Genetics Outreach Rewarding and Impactful

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Students at Fort Hill High School in Allegheny County, MD, participate in an outreach activity. (courtesy Dr. Norris)

I got involved with genetics outreach during my graduate training. Over the last eight years of outreach in high schools across the state of Maryland, I have found that I have the biggest impact on students in rural regions that are far from research institutions, where the students have limited exposure and access to genetics research. At the ASHG Annual Meeting in San Diego last fall, I spent two days before the meeting in Ms. Heather Gastill’s biology classes at the local Mission Bay High School. I had the students identify fish by DNA sequences on paper slips, using real sequencing data from Thomsen et al. For thirty minutes, the students helped each other decode the 100 sequences, creating a barplot of the frequency of different fish species on the classroom whiteboard.

My favorite moment was when each class: (1) calculated the time it would have taken them to go identify the full dataset (millions of sequences), (2) laughed at the absurdity of how long it would take them, and then (3) was mesmerized by my slide that showed how I did it in a couple of hours on my laptop with just a few sentences of bioinformatics code. After each class, a few students would ask me how they can become a bioinformatician. That is why I love genetics outreach.

Ready to join the Genetics Engagement & Education Network? Learn more on the ASHG website.

Alexis Norris, PhD, joined the ASHG Information & Education (I&E) Committee during her postdoctoral training at the Johns Hopkins School of Medicine. She is currently a Bioinformatician at the Food and Drug Administration (FDA).

Inside AJHG: A Chat with Elizabeth Wright

Posted By: Sara Cullinan, PhD, 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 check in with Elizabeth Wright to discuss her paper ‘Practical and ethical considerations of using the results of personalized DNA ancestry tests with middle-school-aged learners’.

Elizabeth Wright, PhD
Elizabeth Wright (photo courtesy Dr. Wright)

AJHG: What prompted you to start working on this project?

Elizabeth: I could give you a long answer about being a former middle school science teacher and what drove me to get a PhD in Science Education, but simply put, I am committed to finding ways for each and every student to see themselves connected to science and each other, and supporting teachers in that work.

AJHG: What about this paper/project most excites you?

Elizabeth: I am equally thrilled and cautious about having adolescents use their own personal DNA to explore who they are genetically, genealogically/socioculturally, and intentionally. We are not all of one thing and none of another. We can use what we know about pieces of ourselves to imagine something new and amazing. We can reveal these pieces of ourselves to our families and friends and see how we are connected to each other and the grander tree of life.

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

Elizabeth: In the previous question I mentioned a bit about what thrills me. I am cautious because the privacy issues surrounding over-the-counter, direct-to-consumer DNA testing are monumental, and ever-shifting. It is both exciting and nerve-wrecking to ask, and watch, young scholars to embark on this intellectual journey. The engagement and electricity in the classroom when young scientists encounter themselves in new and unique ways keeps me going.

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

Elizabeth: I think the most important thing I would say is: you belong here. You belong in science. Your voice, your experiences, your viewpoint are all incredibly important. If you feel left out or unwelcome, create your own community and persevere because you are going to change things.

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

Elizabeth: I’m a Red Sox season ticket holder and I love the game of baseball. I’ve been to baseball games in 27 different MLB parks, and 3 AAA baseball parks. Also, I love Orangetheory Fitness! Base-Push-All Out, that’s good advice.

Elizabeth Wright, PhD, is a postdoctoral fellow in the Jablonski laboratory at Pennsylvania State University.

DNA Day Wins ASAE Power of A Award

Posted By: Mona Miller, ASHG Executive Director

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We are pleased to share that our National DNA Day Essay Contest has received an ASAE Power of A Silver Award. These awards recognize a select number of organizations annually that distinguish themselves with innovative, effective, and broad-reaching programs that positively impact the United States and the world.

ASHG’s DNA Day Essay Contest began in 2005 and is open to students in grades 9-12 around the world. Participants are encouraged to work with their teacher to write a 750-word essay responding to the year’s question. The question is selected with the goal of pushing students to examine, question, and reflect on important concepts in genetics, which are not normally covered in a typical high school biology curriculum. The goal of the question is for students to expand their knowledge of human genetics and to use evidence-based critical thinking in their response.

The contest has grown from around 300 essay submissions in its first years to over a thousand submissions in 2018. This year, ASHG received essays from 43 U.S. states and 23 countries who explored how genetics is informing, shaping, and changing our lives, after which more than 350 ASHG members evaluated the results for accuracy, creativity, and writing.

The contest also engages our members, who act as reviewers and judges for the contest, in an activity that ties them to public outreach and creating the next generation of geneticists. Each year, around 500 members volunteer for this rewarding and worthwhile experience.

The DNA Day Essay Contest has become a signature of ASHG and we are proud of the high number of participants and member volunteers, the satisfaction of our volunteers, and the chance to expand students’ education of human genetics.  We are thrilled to have been recognized for this long-standing program that is an embodiment of ASHG engagement and creativity.

A big thank you to all teachers, students, and member volunteers who have participated over the years!

 

Genetics Outreach and Donations at Calvin Coolidge Senior High School

Posted By: Kanika Pulliam, Senior Manager, Education and Career Development Programs

On the overcast and rainy morning of May 10, the ASHG Education Team (Kelly Ventura, Senior Director of Education and Membership; Karen Hanson, Senior Manager, Education Programs; Evelyn Mantegani, Education Coordinator; and myself) headed to Calvin Coolidge Senior High School, a public school in northwest Washington, DC. The school houses an Academy of Health Sciences, which prepares students for college and careers in health-related professions.

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The ASHG Education Team talked genetics and related careers with students at Calvin Coolidge Senior High School in Washington, DC. (courtesy Kelly Ventura)

As ASHG was preparing to move our main offices to a new building, we discovered a lot of new and gently used lab equipment and supplies in our storage room. There were things like a PCR machine, water bath, and DNA gel electrophoresis items. The supplies were previously purchased to facilitate experiments with educators who developed lesson plans for high school students. With no future plans for the supplies, we decided to donate them to a local high school, and identified Coolidge High School with the help of former ASHG Genetics Education and & Engagement Fellow Teresa Ramirez.

The day of the visit, Kelly and Karen graciously drove in their monster cars for us to load up and transport the many boxes to the school. We were greeted by Zakiya Edens, Coordinator of the Career Academy. She led us to the Academy of Health Sciences room, where we discussed the science program and its strategy to motivate students to come to class and maintain good grades. Students in this special academy participate in additional classes and programs on top of their regular curriculum to prepare for college.

We then met with some academy students, followed by a biology class that was discussing basic genetic concepts and the structure of DNA. Karen and I talked about our roles at ASHG to give the students an idea of career options in the sciences beyond traditional professions like scientist or medical doctor. I shared how they can use their background and love for research to educate scientists and clinicians interested in human genetics. Karen connected to the students by discussing her role as a genetic counselor for the past 25 years and showed them how genetic counselors work with a team of medical professionals to offer the best advice to patients.

We enjoyed the experience of chatting with teachers, administrators, and students. We are now working with Coolidge High School to organize a visit from an ASHG Genetics Education Outreach Network (GEON) volunteer member, to help the teachers go through the donated items and plan experiments for the new school year. GEON is a network of ASHG members who volunteer their time to assist science teachers in building understanding of human genetics among students and the general public.

Kanika Pulliam, PhD, is Senior Manager of Education and Career Development Programs at ASHG. For more on ASHG’s programs for science students, visit our K-12 education website.