Following the birth of the world’s first CRISPR gene-edited babies last year, the concerning specter of a future filled with designer babies has been the focus of many ethical debates. But a new study from an international team of geneticists is suggesting we are probably further away than many realize from being able to effectively genetically select for complex polygenic traits such as IQ or height.
"The ability to do genomic sequencing of embryos is much easier than it was even five years ago, and we know many more gene variants linked to certain traits," explains Shai Carmi, from the Hebrew University of Jerusalem and co-corresponding author on the new research. "But selecting embryos for particular traits is very controversial except when it relates to a serious disease like cystic fibrosis. It raises many issues related to eugenics and unequal opportunities."
While complex gene editing of human babies may be years away from becoming a realistic process, actively selecting embryos based on genetic preferences is already relatively routine in many IVF clinics around the world. Called pre-implantation genetic diagnosis (PGD), the method is generally only used to identify embryos at risk of certain single-gene diseases. In some cases PGD is also used for sex selection.
Identifying monogenic disorders in embryos may be a simple and reasonably reliable technique, but our growing awareness of how different genetic variants relate to human traits led Shai Carmi and his team to wonder how accurate our current ability to identify those traits in embryos actually is. The study focused on two particular traits: height and intelligence. Both traits were selected due to the large volume of pre-existing research identifying influential genetic variants associated with them.
Across a number of computer simulations, the researchers investigated various hypothetical embryos modeled on the genomic profiles of several real-life couples. Based on the gene variants present in the hypothetical embryos the researchers predicted which embryos would result in higher IQ and adult height outcomes.
The conclusions suggest our current genomic knowledge related to height and intelligence can only result in incredibly minor advantages in relation to embryo selection. For example, when selecting an embryo for genes that confer height, an increase of no more than 3 cm (1.2 in) could be achieved, and even then that was not guaranteed.
"There is much about these traits that is unpredictable," says Carmi. "If someone selected an embryo that was predicted to have an IQ that was two points higher than the average, this is no guarantee it would actually result in that increase. There is a lot of variability that is not accounted for in the known gene variants."
The researchers also examined the genetic profiles of a number of multi-generational families to verify the validity of their computer model predictions. It was discovered that children displaying the greatest polygenic score for height only turned out to be the tallest sibling in a family 25 percent of the time. In fact, in five of the 28 families studied, the child with the greatest genetic propensity for height turned out to be shorter than that average height of the rest of the family.
“It has long been feared that genetic information might be used to select embryos based on desire for characteristics such as increased height or intelligence,” says Liz Ormondroyd, a genetic researcher from the University of Oxford. “This computer simulation study shows that, for these complex characteristics, ‘designer babies’ remain in the realm of science fiction.”
The study perhaps offers a clear insight into how complicated certain polygenic traits actually are, and how far we are from being able to effectively manipulate outcomes such as height or intelligence. Joyce Harper, from University College London, suggests this new research is reassuring for those concerned about designer babies becoming a reality, although she does note some companies are already purporting to offer genetic testing for polygenic traits.
“As this study confirms, traits such as height and IQ cannot reliably be detected using genetic testing,” says Harper. “These are complex genetic traits that are also affected by the environment. This is reassuring, as the use of preimplantation genetic testing (PGT) technology for traits is controversial. At least one company is offering PGT for polygenic disorders, such as diabetes and heart disease – so called PGT-P.”
Carmi and the scientists behind the new study note the research highlights the significant practical limits of any gain that could be garnered from trying to select embryos based on polygenic profiling. The ethical debate surrounding this controversial practice is not irrelevant, but this new study stridently affirms how far-off and scientifically complicated the prospect of designer babies actually may be.
The new research was published in the journal Cell Press.
Source: Cell Press via ScienceDaily
