Elizabeth Carr has always been a living symbol of fertility technology’s possibilities. Now she is the face of its challenges.
Carr, 42 years old, is the first baby born by in vitro fertilization in the U.S. Over the years she has told countless audiences how the technology made it possible for her mother to have a baby.
In the weeks since Alabama’s Supreme Court ruled that frozen embryos should be considered children, Carr has called for protections around IVF procedures—extracting eggs, fertilizing them in a lab and transferring an embryo into a uterus—that now account for some 2% of U.S. births annually.
Sen. Tim Kaine (D., Va.) said federal legislation backing IVF access would “enable the Elizabeth Carrs of the world to continue to be born.” Kaine invited Carr to accompany him on Thursday to President Biden’s State of the Union address.
“My life gives people hope,” Carr said.
The Alabama ruling is galvanizing Carr’s work in another way. Carr leads public relations and patient advocacy at Genomic Prediction, which sells genetic tests to screen embryos. Doctors can order tests for patients who want to screen for diseases and abnormalities or get an overall embryo health score. Patients and doctors can use the results to decide which embryos to transfer. Unused embryos can be stored for years. Some get discarded. ...
In Episode 351 of Hidden Forces, Demetri Kofinas speaks with Stephen Hsu, a Professor of Theoretical Physics and Computational Mathematics, Science, and Engineering at Michigan State University. Stephen is also the co-founder of multiple companies, including Genomic Prediction, which provides preimplantation genetic screening services for human embryos, and SuperFocus.ai, which builds large language models for narrow enterprise use cases.
This is a conversation about some of the most important advancements and trends in genomic science and artificial intelligence, including the social and ethical dilemmas arising from implementing these technologies at scale. Stephen and I discuss the competitive landscapes in both industries, how America’s geostrategic competition with China is driving tradeoffs between innovation and safety, the risks and opportunities that these revolutionary technologies pose, and how the world’s largest companies, economies, and military powers can work together to reap the benefits of this revolution while averting some of their most disastrous potential consequences.
Polygenic screening and its discontents
... But monogenic and chromosomal screening can only address a part of disease risk because most health conditions that afflict people are polygenic, meaning they are not simply caused by one gene or by a chromosomal abnormality. Instead, they are caused by a huge number of small additive effects dispersed throughout the genome. For example, cancer, schizophrenia, and diabetes can be best predicted by models using tens of thousands of genes.
A polygenic risk score (PRS) looks at a person’s DNA to see how many variants they have associated with a particular disease. Like BRCA1, polygenic risk scores are typically not determinative: “Polygenic screening is not a diagnosis: It is a prediction of relative future risk compared to other people.” In other words, someone with BRCA1 has a higher risk than someone without, and someone with a high breast cancer PRS has a higher risk than someone with a lower breast cancer PRS. But in principle, BRCA1 is just one gene out of thousands contributing to a PRS, with each bit contributing a small part of a total risk estimate. ...
... Recently, a group of European scientists argued that polygenic screening should not be available to couples because it will lead to stigmatization, exacerbate inequalities, or lead to confusion by parents about how to weigh up information about risks before they decide which embryo to implant. These are indeed challenges, but they are not unique to embryo selection using polygenic scores, and they are not plausible arguments for restricting the autonomy of parents who wish to screen their embryos for polygenic traits. Furthermore, from an ethical perspective, it is unconscionable to deny polygenic screening to families with a history of any disease whose risk can be reduced by this lifesaving technology.
Many new technologies are initially only available to people with more money, but these first adopters then end up subsidizing research that drives costs down and quality up. Many other medical choices involve complexity or might result in some people being stigmatized, but this is a reason to encourage genetic counseling and to encourage social tolerance. It is not a reason to marginalize, stigmatize, or criminalize IVF mothers and fathers who wish to use the best available science to increase the chances that their children will be healthy and happy.This is a comment on the article:
1) They don't want to admit that some people are better than others, inherently. Boo hoo.
2) You put a scorecard of embryos in front of everyone, and everyone has a pretty good ballpark estimate of which are better and which are worse. Nobody is going to pretend equality is true when they are choosing their kids genes.
3) So bad feels.
4) Must therefore retard all human progress and cause immense suffering because don't want to deal with bad feels.
That's the anti-polygenic argument in a nutshell. I don't expect it to be very effective. At best it will cause it to take a bit longer before poor people have access.
Smart Leftists vs Dumb Leftists:
— steve hsu (@hsu_steve) November 13, 2022
Who qualifies as former?
How about Soros, the top donor to the Democratic Party?
A few years ago I gave a talk on genomics (including of cognitive ability) to top leadership at Soros Fund Management.
Reaction: overwhelmingy positive 🤔 1/
Smart Leftists know things which they cannot admit in public.
— steve hsu (@hsu_steve) November 13, 2022
Dumb Leftists fight over these things like retards scuffling in the hallway.
2/
See, e.g., https://t.co/iiqc9TM5ue pic.twitter.com/IUIKp5Y60L
If you are not a billionaire, but want to know what I told the Soros people, see the talks I've given at Berkeley Innovative Genomics Institute, DeepMind, OpenAI, Janelia Farms (HHMI), Allen Institute, Cold Spring Harbor, etc.
— steve hsu (@hsu_steve) November 13, 2022
Links below. 3/https://t.co/xrvxOm1Ld4
Note, the forward looking statements I made in these talks - which were considered bold by the academic genomics community at the time - have almost all been proven correct. 4/https://t.co/vVq4m1Hr11https://t.co/bHYr7vfhdAhttps://t.co/ONdOKyDmQc
— steve hsu (@hsu_steve) November 13, 2022
The impact of progess in polygenic prediction is not confined to academic science.
— steve hsu (@hsu_steve) November 13, 2022
It is going to change how humans reproduce, and even the course of human evolution. 5/https://t.co/Z1fr1zMhD3 pic.twitter.com/iJx5yoZRaR
New results from Taiwan Precision Medicine Initiative, a mega-biobank (>500k already genotyped).
— steve hsu (@hsu_steve) October 25, 2022
Diabetes predictor trained in TW as powerful as EUR-trained PRS. Breast Cancer PRS validated in TW. More!
Poster for Amer. Soc. Hum. Genetics#ASHG2022 pic.twitter.com/kU7RmHGlVi
Monte Carlo projections for PGS performance in current and future biobanks.
— steve hsu (@hsu_steve) October 25, 2022
Also methods comparison between sparse training algos: L1, PRScs, elastic net, ..
All of Us and TPMI (Taiwan) will close PGS gap for non-Euro ancestry groups!
Amer. Soc. Hum. Genetics#ASHG2022 pic.twitter.com/Pu7UfeaKEN
The Times of Israel
14 October 2022, 1:27 pm
Designer babies? Hi-tech preimplantation genetic testing may soon come to IsraelFor generations, the Yu family of Shanghai has suffered from type 2 diabetes. But this summer, as reported in the China Daily, the family welcomed a baby with a better chance of avoiding this disease.
These rosier prospects are the result of a recent breakthrough in assisted reproduction that was advanced with the help of Israeli scientists, called preimplantation genetic testing for polygenic diseases (PGT-P). In addition to China, PGT-P is also gaining ground among couples in the United States who wish to improve health outcomes for their future children. But in Israel, it is illegal.PGT-P is carried out on an embryo during in vitro fertilization (IVF), prior to its transfer from the Petri dish to the womb. Viable embryos with the probable lowest disease risk can then be selected for implantation.
Since this innovative testing takes into account a complex combination of factors that are not broached in more traditional testing, in some ways it’s almost like an educated guess. Accordingly, polygenic screening is not a diagnosis: It is a prediction of relative future risk compared to other people.
Israeli academics have published peer-reviewed research advancing the science behind polygenic screening, including Shai Carmi, Ehud Karavani, Or Zuk, Gil Atzmon, and Einat Granot-Hershkovitz.
But Start-Up Nation is not yet implementing this cutting-edge tech in the field of fertility. Although fertility treatments are subsidized by the Israeli government, it is still unclear whether Israeli couples ever will have access to the procedure, which screens for polygenic diseases such as diabetes, heart disease and cancer — or whether they would even want it.
PGT-P is different from prior technology in important ways, creating new opportunities and challenges for parents while raising profound ethical dilemmas for society. Similar to older forms of testing, PGT-P relies on analyzing genetic material from embryos created through IVF before implantation and checking them for certain diseases and conditions. The information then helps the parents and doctors decide which embryos to implant.
However, the biggest difference between PGT-P screening and earlier forms of genetic testing is that the prior tests checked for genetically simple conditions such as Down syndrome, cystic fibrosis, or Tay Sachs disease. These diseases, which are serious or fatal, have extremely high “penetrance,” which means that if the gene mutation is seen in the embryo’s DNA, it is nearly certain that the child will have that condition. The appearance of the disease-linked gene is the basis of a clear diagnosis.
This “simple” genetic screening has already borne fruit in the Jewish community: Decades ago, babies in the Ashkenazi Jewish community were nearly 100 times more likely to be born with Tay Sachs than babies in the general US population. Today, because of genetic screenings, the disease is “virtually wiped out.”
In contrast, PGT-P screening can’t tell you with assurance if an embryo will develop a genetic disease such as cancer or Crohn’s disease. That’s because this new screening checks for polygenic diseases – complex conditions caused by the combined impact of possibly thousands of different genes, as well as lifestyle and other environmental factors.
Instead of a clear diagnosis, prospective parents receive a “polygenic risk score,” basically the probability of a child developing a certain disease or condition.
Noa and her husband went through 10 IVF cycles to build their family. “We now have two wonderful boys,” she says.
If I had an opportunity to reduce disease risk in my kids, I would do it
She knows what she would have said if doctors had offered her polygenic screening: “I want that technology.” As a speech therapist who works with kids facing a lot of health challenges, she was very worried about what her own kids would face.
“If I had an opportunity to reduce disease risk in my kids, I would do it. It would definitely help my peace of mind as a mother. Everyone here in Israel should have the option of using it,” Noa says.
No clear-cut answers
Scientists at the US-based Genomic Prediction, Inc. published an article in 2019 describing the “first clinical application” of polygenic screening of embryos. Genomic Prediction is a polygenic screening company based in New Jersey that partners with various IVF clinics around the world.
However, to date, the Israeli Health Ministry has yet to even issue a statement on the use of polygenic screening on embryos.
For some, the fact that PGT-P screening isn’t available, or even legal, in Israel is somewhat counterintuitive, given Israel’s prominence in the fields of both assisted reproduction and genetic testing.
Israelis undergo more rounds of IVF per capita than any other nation in the world. This is largely due to religious and cultural norms that are highly supportive of child-bearing, combined with the nationally financed healthcare system that provides full coverage for as many IVF cycles as needed, up to two children per family.
In addition, “in Israel there is a lot more openness to preimplantation genetic testing in general because of the high prevalence of various disease mutations in our community,” says Carmi, an associate professor at the Hebrew University School of Public Health and Faculty of Medicine.
Today, Carmi is a leading researcher on the accuracy of polygenic screening. As part of his post-doctoral project at Columbia University in New York, he helped generate important genetic sequencing data for Ashkenazi Jews.
Israel’s embrace of most genetic testing is reflected in the Israeli Health Ministry’s website, which lists dozens of recommended genetic screenings, broken down by ethnic sub-community. But these screenings are for monogenic disorders, easily diagnosed by looking for a single gene mutation.
“In Israel, the Health Ministry controls which diseases can be screened for, and candidate variants need to have high penetrance and lead to diseases with severe symptoms,” says Carmi.
Playing the odds
Miri is a consultant originally from central Israel. Although she did not have any known fertility problems, she chose to undergo IVF specifically because it would allow her to screen for a certain hereditary disease. She and her husband are both carriers of a rare mutation, so a natural conception meant a 25 percent chance of the fetus suffering from this generally fatal condition.
“For me, it was a choice between the extra physical hardship of IVF, or the extra emotional hardship of a pregnancy where, for months, we would not know if the baby would have this disease,” Miri said.
In contrast, PGT-P can’t provide conclusive information, because in the context of polygenic diseases like diabetes and heart disease “nothing is deterministic,” says Carmi.
According to Carmi, a child may develop the condition or may not, and non-genetic factors can certainly affect the outcome. Based on his peer-reviewed research on statistical modeling of polygenic screening, though, Carmi notes that “you can get quite a substantial risk reduction.”
The “relative risk reduction” projected to be accomplished by PGT-P varies depending on the disease. However, according to a 2021 research paper by Carmi and his collaborators, for schizophrenia and Crohn’s disease, around a 45% relative risk reduction is achievable for parents testing five embryos and choosing the best scoring, compared to implanting a randomly chosen one of the five.
The testing, of course, comes with a fee: Costs vary, but Genomic Prediction in New Jersey charges a $1,000 up-front fee, plus $400 per embryo analyzed. Of course, this is an add-on cost for people already doing IVF, which in the US can cost up to tens of thousands of dollars per cycle.
Pricing can get even more complicated, however, because different services end up bundled together, or are offered as add-ons once related costs are already accounted for. But one of the earlier forms of embryonic screening (PGT-A, which checks for aneuploidies, giving rise to Down syndrome for example) can cost several thousand dollars.
By contrast, carrier screening, which is a blood test performed on the parents to check for “simple” monogenic-disease carrier status, costs only several hundred dollars, and is often also covered by insurance.
In Israel, for couples whose family history or carrier-screening blood tests reveal a heightened risk for having children with a specific monogenic disease, the Health Ministry promotes the benefits of traditional genetic testing of embryos prior to implantation in the womb.
According to its website, “Pre-implantation Genetic Diagnosis (PGD) is today considered to be one of the practical options for couples who are at high risk for giving birth to a baby with a chromosomal abnormality or a genetic disease. This is because the process allows pregnancies to be achieved with healthy fetuses, and avoids the need for pregnancy termination, a procedure that constitutes a problem for many couples for religious, ethical and/or moral reasons.”
The nuts and bolts
PGT-P was developed using artificial intelligence technology applied to huge databases containing the genetic and health information of hundreds of thousands of people. Statistical data analysis of DNA and health outcomes allows scientists to see which complex genetic patterns more frequently show up in individuals who also develop a certain disease, such as schizophrenia. By genetically analyzing an embryo and then comparing its genetic information to this population data, the embryo’s polygenic risk score can be calculated for a given disease. This can already be done for a great many common diseases, with varying levels of predictive power, and as genetic databases grow, the reliability of these risk scores will continue to improve.
The couple also receives the raw data about their embryos’ genes and risk scores, so if they prefer to implant the embryo with the lowest risk of type 2 diabetes rather than the lowest combined disease risk, they can do that
“For prospective parents undergoing IVF and electing to use polygenic screening, somewhere between 10 and 20 polygenic risk scores are combined in a weighted average, with more serious diseases given greater weight in the final figure. This averaging provides a single number for each embryo — a health index — that can be used to rank the available embryos, so that the one with the best health index can be implanted,” says Carmi.
“Of course, the couple also receives the raw data about their embryos’ genes and risk scores, so if they prefer to implant the embryo with, let’s say, the lowest risk of type 2 diabetes, rather than the lowest combined disease risk, they can do that,” says Carmi.
An emotional decision
Michal Amrani, 32, lives in the central Israeli town of Ramat Hasharon and is working toward a master’s degree in chemistry from the Weizmann Institute. Through a four-year IVF process, she and her husband Sarel welcomed a son, and later, a set of twins. They say they are unlikely to use polygenic screening, even if it becomes available in Israel.
“As it is, we opted not to do some of the genetic testing that was already available to us,” Amrani says. “I work in science, so I am more open to these things, but my husband doesn’t really like all these genetic tests. For him, there’s risk in lots of things, and his optimistic nature helps him be comfortable that things will work out.”
Others, like Noa, are more interested in trying out preimplantation polygenic screening of their embryos, but even if Israel would change its rules to allow it, it’s a tricky issue. First, there are concerns about the psychological difficulties that this technology may pose for prospective parents.
Rona Langer Ziv is a social worker and cognitive behavioral psychotherapist who counsels IVF patients — both couples and singles — at a large Israeli hospital, as well as through her private clinical practice.
“Due to the potential implications of this new technology,” she says, “I would be concerned about a higher risk for depression and anxiety among the IVF patients.”
“Even if they feel they understand what they are signing up for at the beginning of the journey, they may not appreciate the emotional, ethical, and psychosocial implications of polygenic screening several IVF cycles down the road,” says Langer Ziv. “They may find themselves worrying that the embryos’ scores are not good enough, or that they won’t have any viable embryos left to choose from.”
Even if they feel they understand what they are signing up for at the beginning of the journey, they may not appreciate the emotional, ethical, and psychosocial implications of polygenic screening several IVF cycles down the road
Because polygenic screening predicts relative risk rather than providing an affirmative disease diagnosis, “women, especially those over 40 who may have very few embryos to work with, end up facing a serious dilemma — they may be discarding an embryo that could have resulted in a healthy child,” says Langer Ziv.
Amrani is in a similar situation. She and her husband are ready for more kids, but right now they have just one embryo available, so that’s the embryo they will try to implant. Even though she won’t be using polygenic screening, Amrani says that “it does sound very innovative. It’s nice that there’s something like this.”
Social worker and cognitive behavioral psychotherapist Rona Langer Ziv. (Courtesy) Indeed, Langer Ziv acknowledges that some people would find polygenic screening appealing, particularly those with higher education levels.
“There’s definitely coolness in the technology. It’s scientifically advanced, and it could offer interesting health insights about your future children. Everyone would theoretically like to use a technology that potentially predicts a more healthy child, although there is disagreement among fertility specialists about the benefits involved,” Langer Ziv says.
“And for some IVF patients, it might also provide a feeling of control during a process that involves so much stress, uncertainty, luck, and randomness,” she says.
Risk of eugenics
Regardless of how polygenic screening would be received by potential consumers, there are grave concerns about the impacts of this new technology on society. Various ethical issues have been raised for decades about older forms of genetic screenings, including fears of stigmatizing those living with genetic diseases, and questions about equitable access to these technological advances.
Perhaps the most significant ethical concern, and one that looms larger with polygenic screening than with older tests for monogenic diseases, is the potential for eugenics. This is the infamous and dangerous philosophy, practiced in Nazi Germany and elsewhere, that society should try to promote the creation of the most genetically “superior” babies.
Miri and her husband now have a baby boy and are looking forward to having more children — they still have three embryos to choose from. Asked whether she would be interested in polygenic screening if it became available in Israel, Miri says she’s unsure.
“I would love to see less suffering in the world from diseases. But where do we draw the line?” she says.
Indeed, the potential for eugenics is most stark when screenings cross over from the realm of disease prevention to the world of intelligence and aesthetic traits such as height or eye color. As such, some laboratories preemptively claim they will only screen for health concerns: An American polygenic screening company currently states that it does not test for “high IQ,” nor for “purely cosmetic traits such as hair color and eye color.”
But complicating the “noble” stance, genetic researchers have shown that “IQ is negatively correlated with most psychiatric disorders [and] positively correlated with autism and anorexia,” meaning that a high IQ comes with a lower risk of most psychiatric diseases and a higher risk of certain other neurological and mental health conditions.
As such, while some companies may currently refuse to offer IQ screening, it is not hard to imagine a health-based argument for loosening such protocols in the future, particularly as society becomes more used to the practice of PGT-P.
Similarly, a large study was published this year by researchers at Brown University and Peking University that found that “light eye colors were associated with high risks” of certain forms of skin cancer. Again, one can picture checks for eye color making their way into future genetic screenings through a backdoor of disease relevance.
In Carmi’s view, the responsible way for Israel to approach the prospect of polygenic screening is a gradual one.
“Ideally, we would start by recruiting Israeli participants for local academic research, with oversight by the Health Ministry,” Carmi says. “Once we develop more insight into how predictive polygenic screening is in our population, the relevant stakeholders — including patients, professional organizations, and regulators — can balance competing interests and local values, and come up with tailored guidance on its use in Israel.”
For some Israeli citizens, of particular concern is the idea of the wealthy trying to create perfect babies.
“If polygenic screening came to Israel, I would want to see a lot of regulation about who gets to use it, how it is used, and what reasons it is used for,” Miri says.
See also
WIRED: Genetic Screening Now Lets Parents Pick the Healthiest Embryos
Genomic Prediction in Bloomberg
The transcript excerpts below are from my recent conversation with Brian Chau (aka Cactus Chu) on his podcast.
— steve hsu (@hsu_steve) September 28, 2022
Segments begin at 47m and 1h07m.
They have been lightly edited.https://t.co/RJ68FasfJchttps://t.co/TnSuNaxhnQ
Sibling Variation in Phenotype and Genotype: Polygenic Trait Distributions and DNA Recombination Mapping with UK Biobank and IVF Family Data
L. Lello, M. Hsu, E. Widen, and T. Raben
We use UK Biobank and a unique IVF family dataset (including genotyped embryos) to investigate sibling variation in both phenotype and genotype. We compare phenotype (disease status, height, blood biomarkers) and genotype (polygenic scores, polygenic health index) distributions among siblings to those in the general population. As expected, the between-siblings standard deviation in polygenic scores is \sqrt{2} times smaller than in the general population, but variation is still significant. As previously demonstrated, this allows for substantial benefit from polygenic screening in IVF. Differences in sibling genotypes result from distinct recombination patterns in sexual reproduction. We develop a novel sibling-pair method for detection of recombination breaks via statistical discontinuities. The new method is used to construct a dataset of 1.44 million recombination events which may be useful in further study of meiosis.
Here are some figures illustrating the variation of polygenic scores among siblings from the same family.
The excerpt below describes the IVF family highlighted in blue above:
Among the families displayed in these figures, at position number 15 from the left, we encounter an interesting case of sibling polygenic distribution relative to the parents. In the family all siblings have significantly higher Health Index score than the parents. This arises in an interesting manner: the mother is a high-risk outlier for condition X and the father is a high-risk outlier for condition Y. (We do not specify X and Y, out of an abundance of caution for privacy, although the patients have consented that such information could be shared.) Their lower overall Health Index scores result from high risk of conditions X (mother) and Y (father). However, the embryos, each resulting from unique recombination of parental genotypes, are normal risk for both X and Y and each embryo has much higher Health Index score than the parents.This case illustrates well the potential benefits from PGS embryo screening.
...This new sibling-pair method can be applied to large datasets with many thousands of sibling pairs. In this project we created a map of roughly 1.44 million recombination events using UKB genomes. Similar maps can now be created using other biobank data, including in non-European ancestry groups that have not yet received sufficient attention. The landmark deCODE results were obtained under special circumstances: the researchers had access to data resulting from a nationwide project utilizing genealogical records (unusually prevalent in Iceland) and widespread sequencing. Using the sibling-pair method results of comparable accuracy can be obtained from existing datasets around the world -- e.g., national biobanks in countries such as the USA, Estonia, China, Taiwan, Japan, etc.
WIRED: ... Companies such as Genomic Prediction are taking this process much further, giving parents the power to select the embryo they believe to have the best fighting chance of survival both in the womb and out in the world. At the time of writing, Genomic Prediction works with around 200 IVF clinics across six continents. For company cofounder Stephen Hsu, the idea behind preconception screening was no eureka moment, but something he and his peers developed gradually. “We kept pursuing the possibilities from a purely scientific interest,” he says. Over time sequencing has become cheaper and more accessible, and the bank of genetic data has become ever greater, which has provided the opportunity to easily apply machine learning programs to seek out patterns, Hsu explains. “You can have typically millions of people in one data set, with exact measurements of certain things about them—for instance how tall they are or whether they have diabetes—what we call phenotypes. And so it’s relatively straightforward to use AI to build genetic predictors of traits ranging from very simple ones which are only determined by a few genes, or a few different locations in the genome, to the really complicated ones.” As Hsu indicates, the crucial difference with this technology is that it’s not just single mutations like cystic fibrosis or sickle cell anemia that the service makes its calculations on. The conditions embryos are screened for can be extremely complicated, involving thousands of genetic variants across different parts of the genome.
In late 2017, Hsu and his colleagues published a paper demonstrating how, using genomic data at scale, scientists could predict someone’s height to within an inch of accuracy using just their DNA. The research group later used the same method to build genomic predictors for complex diseases such as hypothyroidism, types 1 and 2 diabetes, breast cancer, prostate cancer, testicular cancer, gallstones, glaucoma, gout, atrial fibrillation, high cholesterol, asthma, basal cell carcinoma, malignant melanoma, and heart attacks. ...
Two useful references:
Polygenic Health Index, General Health, and Disease Risk
Complex Trait Prediction: Methods and Protocols (Springer 2022)
Polygenic Health Index, General Health, and Disease Risk
We construct a polygenic health index as a weighted sum of polygenic risk scores for 20 major disease conditions, including, e.g., coronary artery disease, type 1 and 2 diabetes, schizophrenia, etc. Individual weights are determined by population-level estimates of impact on life expectancy. We validate this index in odds ratios and selection experiments using unrelated individuals and siblings (pairs and trios) from the UK Biobank. Individuals with higher index scores have decreased disease risk across almost all 20 diseases (no significant risk increases), and longer calculated life expectancy. When estimated Disability Adjusted Life Years (DALYs) are used as the performance metric, the gain from selection among 10 individuals (highest index score vs average) is found to be roughly 4 DALYs. We find no statistical evidence for antagonistic trade-offs in risk reduction across these diseases. Correlations between genetic disease risks are found to be mostly positive and generally mild. These results have important implications for public health and also for fundamental issues such as pleiotropy and genetic architecture of human disease conditions.
https://www.medrxiv.org/content/10.1101/2022.06.15.22276102v1
The days of our years are threescore years and ten; and if by reason of strength they be fourscore years, yet is their strength labour and sorrow; for it is soon cut off, and we fly away
Psalm 90:10
