After becoming a parent, I realized that all parents want their children to have a wonderful life. If we could choose, many parents would want them to have the perfect job, the perfect kids and ultimately a long healthy life. As our kids grow, we hope that our kids do not have the same health issues or mental health problems that may run in our families.
At the same time, genomic information often has been seen as being deterministic for our health: that our genetics define who we are and that our future is fully determined by the tiny pieces of information that our parents passed to us. We know that while genetics can be a helpful guide, there are so many other factors that contribute to our health, from what we eat, to what bacteria we have in our guts, to the social and economic environments we live in.
To that end, in the past few years, we have started to see the power of big data in the genomic space. Many groups have published information on how to use polygenetic risk scores to better understand our underlying risk factors which hopefully will lead to treatments or the tools to live a longer healthier life.
Now, companies are starting to use modern genetic tools to predict risk for common diseases in our children. At-home kits are available that try to predict a parent’s risk for passing along certain risk factors for diseases like stroke, diabetes, schizophrenia, heart disease or cancer to their children. Some parents want to know the risk factors they carry and want to try to reduce the chances that their kids will have to face those concerns.
A Brief PRS (Polygenic Risk Scores) Explanation
Polygenetic risk scores, or PRS, are estimates of an individual’s chance, based on their genetics, to develop a multifactorial disease. Multifactorial diseases are those that are caused by a combination of genetic, lifestyle and environmental factors. Most PRS only look at the genetics piece of the puzzle, and only represent some of the genetics pieces. That is because there are often hundreds, even thousands, of genetic variants that can play a part in multifactorial disease, and we don’t yet understand all of them. Essentially, PRS may have a fairly small overall estimation of risk for someone actually getting a disease. Social or environmental factors may have a much greater impact on risk for future children. That said, if we could do something to mitigate risk as a parent, would we, and what actions should we take?
In-Vitro Fertilization with Preimplantation Genetic Testing
In-vitro fertilization (IVF) is the process where we retrieve eggs and fertilize them with sperm outside of the body. After five days of development, we can take cells from a growing embryo and analyze the cells to look for genetic variants. This testing is called preimplantation genetic testing (PGT). Currently, PGT is available to test for many diseases with a known single genetic variant (we call these monoallelic diseases). More often, this technology is used to screen embryos for chromosome abnormalities that most often result in failed IVF cycles or miscarriage. At the present time, the testing will only look at a limited amount of genetic information in the embryo but will not alter or change it in any way. Therefore, the testing does not to change what the embryo has, but instead gives us more information. It would be up to the parents and providers to discuss the results and whether or not the risk factors found would be suitable for transfer.
When considering testing for multifactorial conditions using PGT, as a society we must begin to have the conversation around these and likely many other important topics.
- Inequity in access to data for PRS and availability of testing for all: Current databases are insufficient to provide equitable scoring and PRS tests for all patients therefore this resource is inherently not universally able to be used by all patients.
- Chromosome issues: Outside of the IVF world, it is not well understood that a significant proportion of embryos have aneuploidy (the wrong number of chromosomes). Therefore, in any IVF cycle, there are only a small number of embryos that could result in a viable baby.
- Cost of IVF: The cost of IVF is prohibitive for many people. In addition, each IVF cycle only produces a small number of euploid (correct number of chromosomes and therefore likely viable) embryos. For us to harness the power of PRS in embryos, in many cases, we would need a significant number of embryos to choose from. In most cases, multiple IVF cycles likely would need to be done in order to proceed with finding the embryo with the ‘best’ potential outcome via PRS.
- Sequencing DNA from embryos: In most cases, we are not reading or sequencing the DNA at the embryo level. Because of the very small amount of DNA, there is concern for genetic content to be overlooked or misidentified. While this likely will be a technicality that can be overcome with scientific advancements, there is always going to be some concern about how accurate the sequencing is going to be when we start with so little DNA.
- What would you pick: This is likely the biggest concern. Even if we have lots of embryos to pick from, we solve the sequencing problems and IVF is freely available for everyone--it still comes down to what would you pick for your child. As a parent, would I rather have a child with an increased risk for diabetes or schizophrenia? Stroke or cancer? How would I pick? And who decides what is the best outcomes? Is it totally up to us as parents? Who does the counseling prior to making those decisions and does picking one risk over the other have any long term financial or emotional risks?
- Justice, ethics and societal concerns: It is critically important to take a step back and also consider the ethics of this testing. First, most of the studies that have identified genetic variants that are part of PRS were done in primarily white populations. So, any technology that incorporates PRS can potentially create a class system where only white people would have access to the technology. In addition, because of the cost of IVF, this testing would be too expensive for most of society. Finally, there may be long term harm. For example, how would a child process that their parents selected them to be at an increased risk for a certain disease, because the parents thought it was better than another disease or condition?
There is power in information and many parents are concerned about these multifactorial conditions for their children. Accessing more information about their children or potential children could be both a blessing and a curse. With these technologies, it is important for parents to have help working through whether they want or should act upon the information for multifactorial diseases. Genetic counselors are uniquely trained to have these complex conversations with families. They also will include familial information in the conversation because there is more to family risk and inherited dynamics than just a genomic profile.
If you are reading this and have questions that are unanswered, please find a local genetic counselor through findgeneticcounselor.com.
Our understanding of the genome will continue to expand. These technologies are only in their infancy. What is important is that we continue to look at both the benefits and harms this information may have both to an individual, but also society as a whole. We should always proceed with caution while being inclusive in the discussion about how we use these technologies for the greatest good.
Additional Resources
Using genetic testing to select embryos with lower risk for schizophrenia: What should I know?
Jason Flanagan, MS, CGC, is NSGC’s Reproductive Health Expert. He is one of only several genetic counselors in the country with a focus on infertility genetics.
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