Science

Genetic risk scores open a host of concerns and implications

Scientist Andy Peterson works with stem cell cultures at the iPSC Reprogramming and Human Stem Cell Gene Editing Service at the Waisman Center at the University of Wisconsin-Madison on Nov. 29, 2018. The service offers CRISPR/Cas9 gene editing, which is short for clustered regularly interspaced short palindromic repeats and the CRISPR-associated protein 9. (Photo by Jeff Miller / UW-Madison)
Scientist Andy Peterson works with stem cell cultures at the iPSC Reprogramming and Human Stem Cell Gene Editing Service at the Waisman Center at the University of Wisconsin-Madison on Nov. 29, 2018. The service offers CRISPR/Cas9 gene editing, which is short for clustered regularly interspaced short palindromic repeats and the CRISPR-associated protein 9. (Photo by Jeff Miller / UW-Madison) Image By: Jeff Miller

A world where we can predict what traits and diseases that a baby will be born with is nearly upon us. With the expanding availability of genetic data, researchers in both universities and industry are trying to figure out the complicated relationship between our DNA and human health. For traits and diseases that reflect the interaction between many genetic and oftentimes environmental risk factors, these sorts of predictions are more difficult to make.

Scientists use genome-wide association studies with very large sample sizes to calculate polygenic scores, which correlate genetic factors with complex traits, like height or BMI, and risk for complex diseases, like heart disease or autism.

“Almost everything you can think of is highly polygenic — meaning [that] many, many, many genes or hundreds of thousands of genetic locations could be affecting [a complex trait],” Jason Fletcher, a UW-Madison professor of public affairs studying some of the ethical, legal and social implications of genomic science, said.

Since an individual’s genome generally does not change over the course of their lifetime, polygenic scores could offer an avenue for identifying individuals for specialized treatments or early interventions, Fletcher adds.

“The positive case might be something like thinking about an instance where there is polygenic score for dyslexia and potentially being able to use a score like that very early in a child's life as a way of collecting individuals who might benefit from specific learning interventions,” Fletcher said.

Intellectual disabilities and learning disabilities often go unnoticed for years, which can leave a child to struggle. 

Lauren Schmitz, a UW-Madison assistant professor of public affairs, also notes that whereas for heart disease, preventative measures are viewed favorably, for intellectual disability the measures used to intervene would need to be carefully considered to avoid stigmatizing individuals.

Schmitz also stresses that although the science is moving fast, the predictive accuracy of these polygenic risk scores varies depending on the trait or disease in question. However, the for-profit, direct-to-consumer DNA testing industry is blurring the lines on what genomic science can say. 

“The way I see it, it's the next frontier in personalized things,” Schmitz said. “I think we're a culture that loves things that are personalized to us — me and my experience — and so I think the genome is the next marketing frontier.”

For example, last November the biotech company Genomic Prediction claimed it could offer polygenic scores for traits including diabetes, heart disease and even IQ as an additional amenity for parents having children through in vitro fertilization. Currently, IVF clinics test fertilized embryos before they are implanted into a uterus to check for inherited genetic disease, like cystic fibrosis or Tays-Sachs disease, or for major chromosome abnormalities that can dramatically decrease the likelihood of a fetus being carried to term. 

The announcement has been met with concern from scientists about the accuracy of these new preimplantation tests as well as the long-term effects of selecting on the basis of these traits.

“There's all sorts of things where we don't even understand how these different mechanisms are operating and how they're correlated with other aspects of the genome,” Schmitz said.

Measurements of intelligence like IQ tests are controversial, and as Angela Saini writes in “Superior: The Return of Race Science,” much of the work correlating educational attainment with genetics has direct ties to the vestiges of the eugenics movement in the early 20th century. Additionally, for many complex traits and diseases in combination with social and environmental factors at play, these polygenic scores are not necessarily an indication that the trait or disease will manifest.

“We should be clear that the scores are not destiny, and there's an upper limit on how predictive it could be,” Fletcher said.

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