In addition to various news sites (GenomeWeb, STAT) and newsletters (e.g. GA4GH) I usually use Rxvist to see what’s new. They show which pre-prints have been generating the most tweets. Except this month, that functionality is broken, so they’re showing the most downloaded articles instead — many of which were not published recently. The top hits in genetics/genomics include face prediction, tutorial for how to construct polygenic scores, ancestry, the effects of an extra X, and single-cell methods.
The stories that have been grabbing my attention are those that link genetics and identity. An excellent interview interview with Dorothy Roberts, author of Fatal Invention: How Science, Politics, and Big Business Re-create Race in the Twenty-First Century, discussed the relationship between genetic ancestry and race. Some selected excerpts
- “Some people think it’s harmless to believe in biological differences between races as long as we don’t value one over another, but the whole point of dividing humans into races is to value some more than others.”
- “Racism isn’t a product of race. Race is a product of racism. People think it’s OK to categorize people by race as long as they’re not racist, but any division of people into supposedly natural races promotes a racist agenda, whether we intend it to or not.”
- On the eugenics movement: “If certain groups of people are at a disadvantage, the thinking went, it must be because of their biological inferiority, not due to state violence and structural inequalities…. Such thinking is still used to explain social inequality in the present: If we believe biology produces these unequal social and economic conditions, then how can they be immoral and in need of change? They are “natural.” The situation can’t be changed.”
- On where you look for explanations: “Have you looked into the fact that black children get expelled and arrested at far higher rates than white children for the same behaviors, like missing school, talking back to a teacher, or roughhousing? Have you looked for any explanations other than within the gray matter of their brains?””
- “If you add a new technology to an already racist system, you’ll get another racist product.”
- And her conclusion: “I don’t believe we should be “color-blind,” that we shouldn’t pay any attention to race. As a political invention, race continues to determine power arrangements and is not going to just go away. We have to dismantle racist institutions to affirm our common humanity. And to do that, we need to understand how the concept of race really functions.”
An interesting study on what happens when white nationalists find out some of their ancestry is not European. A study looked at the responses individuals in a white nationalist group got when they posted their unexpected results — the vast majority of comments they received focused on potential inaccuracies of the testing. The authors conclude: “White nationalism is not simply an identity community or political movement but should be understood as bricoleurs with genetic knowledge displaying aspects of citizen science.”
Genetic identity is key to the debates over donor conception. In the news recently have been reveals of prior mix-ups in sperm donor conception based on genetic testing. One couple whose children were conceived with a donor they didn’t select is revealing of attitudes within the process: ““I didn’t choose someone who has a history of brain cancer in the family. I would never have chosen this donor. They should be ashamed to even have this donor on the website.”” The position of the courts is that there are no grounds to sue if the child is healthy. Meanwhile a Singaporean court defined a new type of loss, a loss of genetic affinity, to deal with a case of a couple who unintentionally ended up with a bi-racial child.
- A study comparing the results from the SNP chips and the NGS data in the UK Biobank finds that SNP chips are very unreliable for rare variants — for variants <0.001% frequency in the biobank, only 16% confirm with sequencing
- A deep-learning approach to probing the role of non-coding variants in autism.The approach focused on finding potential regulatory consequences of the non-coding variants. They have a nifty website.
- A study across five countries places the heritability of autism at around 80%.
- Most hunts for the variants underlying rare disease look for one or a pair of variants in a single gene. New software for locating pairs of pathogenic variants across two genes. Relatedly, an example of a family whose heart issues stemmed from oligogenic inheritance, in this case the affected children inherited two variants from their father and one from their mother, which, in concert, caused heart issues.
- The benefits of using data beyond individuals with no European Ancestry. Large GWAS on diverse datasets: “Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications.” Example of differences (from the accompanying NIH press release): “a strong association was found between a new genomic variant and smokers and their daily cigarette usage in Native Hawaiian participants. However, this association was absent or rare in most other populations.”
- Polygenic scores for cognitive abilities and educational attainment received a further boost from “multi-trait” analysis. “In a representative UK sample of 7,026 children at ages 12 and 16, we show that we can now predict up to 11% of the variance in intelligence and 16% in educational achievement. We also show that predictive power increases from age 12 to age 16 and that genomic predictions do not differ for girls and boys.”
- A variant in the gene SHARPIN, found only in Japanese individuals, increases the risk of Alzheimer’s 6 fold.
- A massive RNA screen shows just how common somatic variants are, across all tissue types.
- New study on the relevance of the microbiome for athletic performance, pointing to the ability of certain bacteria do metabolize lactate. Watch out, WADA.
- A study that identifies epigenetic regions that could be used clinically: “At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample.”
- A nice review of polygenic scores that has a table that compares the relative risk of a disease of those in the top 20% of the score to the bottom 20% of the score
- Does receiving genetic results affect patients psychologically? A paper from the CSER consortium says No: “Our findings across multiple clinical settings suggest no clinically significant psychological harms from the return of ES/GS results.”
- A review article that argues that the intended use of polygenic scores should guide score development.
- Testing what risk information individuals want to know — mostly when mitigations are possible.
- Helix is pivoting to being a partner in population genomics. It launched to great fanfare as a company selling apps on otp of exome sequencing, which presumably was not going well…
- Education alongside genetic test results is often lacking. Here’s a survey that shows that parents of kids with ASD want to know about the accuracy, cost, and benefits of testing.
- Genes for Good, a project that uses facebook to engage with research participants, has sequenced over 20,000 individuals. “Health history and daily tracking surveys are administered through a Facebook application, and participants who complete a minimum number of surveys are mailed a saliva sample kit.”
- EMBL-EBI have released software for genome interpretation, using VEP for variant filtration, called gene2phenotype.
- Muin Khoury of the CDC states their approach to polygenic scores: “We think there is a great potential for PRS to make a health impact in certain clinical scenarios, if we can answer three broad questions using a rigorous scientific agenda: 1) Construct scientifically valid PRS within each population ancestry group using relevant variables; 2) For each intended clinical use of PRS (by disease, population, setting), study the added clinical value of the PRS, and overall balance of benefits and harms of PRS in rigorous research studies (including randomized controlled clinical trials or other rigorous hybrid implementation designs); 3) Assess ethical, legal and social issues that result using PRS in different populations, including policy and reimbursement issues, provider and public education as well health system and organizational readiness.”
- An argument from bioethicist Sandra Soo-Jin Lee that the success of precision medicine requires careful thinking about diversity in order to be trusted.
- In an update to the CRISPR babies story, the variant that He Jiankui engineered into lulu and Nana has been associated with earlier death. Meanwhile a russian scientist is planning to edit more embryos-destined-to-be-babies, targeting the same gene. He thinks that his experiment will be ethical because, unlike He, he will only do the engineering if the mother is HIV positive and hence at risk of passing along the infection. The same scientist has announced plans to edit embryos of deaf parents, both of who carry two variants in the GJB2 gene, so that their children can hear. He has five couples lined up. ““The first human trials should start with embryos or infants with nothing to lose, with fatal conditions,” says bioethicist Julian Savulescu of the University of Oxford. “You should not be starting with an embryo which stands to lead a pretty normal life.””
- 23andMe is piloting asking some customers to link their Electronic Health Records – this would include diagnostic reports, lab results, and medical history.
- Nigerian based 54 Gene wants to build a huge biobank of Africans.
- Veritas has dropped the price of a whole genome from $999 to $599.
- ICE is planning on expanding its DNA testing on the border — the idea is to identify families who do not share genetic relationships, so that they can be labelled as fraudulent.
- Language in a 2020 US spending bill currently includes a ban on human germline modification (it was dropped for a time based on lack of public engagement on the issue).
- Iran is considering making genetic testing free for those families at risk of having a child with a disability. Last year, they announced that genetic testing could reduce births of those with disorders by 50%. These comments are of course out of line with the more familiar mantra that such testing is done only to enhance reproductive freedom.
- Genetic genealogy has helped identify many suspects. Now they have helped convict someone. “The defense could have challenged the use of genetic genealogy on privacy grounds, or as a violation of people’s right to control their personal data. Instead, defense lawyers did not pose a single question about the technique.”
- A call from many experts for the legalization of mitochondrial therapy, which is legal in other countries including the UK.
An interview with George Church touching on many future tech possibilities: “Just being different at all from the middle of the bell curve gives you an advantage in a part of society that cherishes innovation and out-of-the-box thinking.”