The Sequence 10/10-10/16
Polygenic Risk Scores in Men with African Ancestry, Ancestry of Ancient Greek Army, Individuals with Epilepsy Are Having Less Children, President of COVID-19 Testing Lab Found Guilty of Fraud
The utility of polygenic risk scores in men with African ancestry with prostate cancer
A study by Kim et al. looked at the utility of polygenic risk scores to patients from Ghana, Nigeria, Senegal, and South Africa. The purpose was to understand if current scores, which are largely based on European genetic data, are applicable in predicting the risk of prostate cancer in patients with African ancestry.
What is a polygenic risk score?
A polygenic risk score (PRS) is a number, or a ‘score’ that estimates an individual’s risk for a certain condition. They are used in conditions that are caused by changes in many genes, often coupled with environmental factors.
How are they determined?
Let’s use prostate cancer as an example, because that is the condition studied in this article. Scientists created PRSs for prostate cancer by comparing the DNA of patients with and without prostate cancer to determine a ‘collection of genes’ that have more rare variation in the group with prostate cancer that are not there in the group without. Then, they can say, if you have these ‘X’ number of genes, your PRS for prostate cancer is higher.
How did they study it?
The team used covariate-adjusted (i.e. adjusted for age and other variables) odds ratios (OR) of British samples from the UK Biobank (UKBB) and sub-Saharan African (SSA) samples from the Men of African Descent and Carcinoma of the Prostate (MADCaP) to quantify the effectiveness of PRS. Note that the OR described here do not refer to the risks of prostate cancer in Europe and Africa; they refer to the ability of each PRS to distinguish between case and control status within each continental dataset. They compared individuals with high risk scores to individuals with moderate risk scores.
What did they find?
European ORs were larger than African ORs. This indicates that existing prostate cancer PRS were more effective at predicting between cases and controls in men of European descent than in men of African descent.
What’s the takeaway?
Genetic predictions of prostate cancer risks perform poorly if the study sample does not match the ancestry of the original GWAS.
As a reminder, GWAS, or Genome-wide association studies, look at the genome of a large group of people, searching for small genetic variations called single nucleotide polymorphisms (aka SNPs). GWAS look for SNPs associated with certain traits. An example for this study would be, “look, there’s a common SNP in individuals with prostate cancer that’s not in the individuals without prostate cancer”.
Unless well-powered GWAS studies are done in diverse populations, the accuracy and utility of PRS will be sub-optimal in non-European ancestries, exacerbating disparities in risk prediction, and also disease management.
Genetic analysis identifies ancestry of ancient greek army
Researchers used genomic analysis to identify the human remains of 54 individuals from eighth- to fifth-century Sicily, to gain insights into the movement of Classical Greek armies as well as the role of conflict in the ancient Mediterranean. Around this time, Greece was colonizing many areas around the Mediterranean and had a colony in Himera, Sicily.
For those of you who are also lovers of ancient Greek literature like myself, this is also around the time that historians have pinned writing of The Odyssey, the legendary work by Homer.
How did they find out all that?
To begin, genomic analysis helped the researchers to determine the ancestry of these individuals by comparing their DNA with the DNA of 96 modern-day Italian, Greek, and Cretan individuals.
This ‘ancestry matching’ is done by looking at short pieces of DNA across the genome, and comparing each piece of DNA to reference genomes (i.e. genomes of people with known ancestry). If the DNA matches the reference genome of a certain population, it’s assigned to that population.
Interesting.
Yes! The genetic analysis identified the burial of soldiers falling both inside and outside the Aegean genetic cluster, showing that many soldiers had ancestral origins in northern Europe, the Steppe, and the Caucasus (i.e. not just Greece). Not surprising, because we already know from other research that mercenaries drawn to the Mediterranean region by the economic opportunity to serve Greek tyrants and participate in Greek wars were not merely itinerant “outsiders” in Greek poleis, but became citizens, and became integrated into the political, cultural, and genetic fabric of Greek life.
The takeaway?
Integrating genetic, archaeological, isotopic, and historical data, these results illustrate the significant role mercenaries played in ancient Greek armies and highlight how participation in war contributed to continental-scale human mobility in the Classical world.
Individuals with epilepsy have less children than general population
Ottman et al. surveyed individuals over 18 years of age with epilepsy of unidentified cause to assess the patients’ attitudes toward having children.
Tell me more.
Patients with epilepsy were asked questions to assess the relationship between the number of children they had/plan to have and three measures of beliefs about genetic influences on epilepsy.
These measures were the following: genetic attribution (GA), or the degree to which participants believed their epilepsy had a genetic cause; their estimate of the chance that the child of a parent with epilepsy would develop epilepsy; and the degree to which concerns about the chance of having a child with epilepsy influenced their reproductive decisions.
What did they find out?
The number of children people aged 45 and younger had was strongly associated with both GA and estimated offspring risk. Those in the highest GA quartile had only about half as many offspring as those in the lowest quartile. Additionally, participants who responded that the chance of having a child with epilepsy had a strong/ very strong influence on their reproductive decisions had only 60% as many offspring as others, and this estimate was unchanged after adjustment for potential confounders.
The takeaway?
When the perception of risk to their children increased in participants aged 18-45, they decided to have less children. It will be important to do further research to understand the emotional impacts of these decisions on individuals and their families as it relates to their medical history.
Think you should talk to a genetic counselor to understand the risk of passing a genetic condition on to your child? Find one here.
President of COVID-19 testing lab found guilty of fraud
Mark Schena, The former president of Arrayit Corporation, has been convicted for taking part in a $77 million COVID-19 and allergy testing scheme.
Tell me the story.
Arrayit mostly performed allergy testing prior to 2020. Then in 2020, once the pandemic slowed the demand for allergy testing and increased demand for COVID-19 testing, Schena falsely announced that Arrayit had a test for COVID-19 before one was actually developed. Then once it was developed, he falsely claimed that the Arrayit’s COVID-19 test was more accurate than a PCR test for identifying infections, while in fact all along the Food and Drug Administration had informed him that the Arrayit test was not accurate enough to receive an Emergency Use Authorization for use in the United States.
It gets more elaborate. Remember that Arrayit mostly did allergy testing. To capitalize on the testing the lab already performed, Schena falsely claimed that Dr. Anthony Fauci and other prominent government officials had mandated testing for COVID-19 and allergies at the same time and required that patients receiving the Arrayit COVID-19 test also be tested for allergies. Excuse me?
That’s a lot.
It is. But there’s more. It came to light that Schena was in fact submitting fraudulent claims to Medicare and private insurances long before the pandemic hit… for unnecessary allergy testing, of course. Arrayit ran allergy screening tests for 120 allergens on patients, even if they didn’t need it. Schena payed kickbacks to get more people to use Arrayit, and also lied about what the test actually did. He marketed it as an accurate diagnostic test when it is in fact not a diagnostic test at all.
Arrayit billed more per patient to Medicare for blood-based allergy testing than any other laboratory in the United States, and billed some commercial insurers over $10,000 per test.
How much money are we talking total?
All in all, Schena was convicted for misleading investors, committing health care fraud, and paying illegal kickbacks in connection with the submission of over $77 million in false and fraudulent claims for COVID-19 and allergy testing.