I continue to struggle to find a format for these round-ups. I am finding the division Science/Applications/Regulation useful, but there a few stories that never quite fit that pattern. I realized that these are mostly the controversial ones, and so I have carved off a section dedicated to the eyebrow raising.

Controversy

• Elizabeth Warren underwent genetic ancestry testing, in order to prove a genetic connection to her claim of Native American ancestor. Her move has been widely covered, and criticised. It throws light on the connection between genetics and identity. Here is an interesting piece comparing the relationship between genetics and cultural identity in the aboriginal populations of Australia and the US.
• Nature News reports on the The approach to predictive medicine that is taking genomics research by storm. One of the leading scientists behind polygenic scores, Peter Visscher, a geneticist at the University of Queensland, states that “I’m absolutely convinced this is going to come sooner than we think.” Myriad has begun including a polygenic score for breast cancer on its reports, in something that is rather convenient for sales, “One of the strengths of these scores is that they provide a result for everyone, says Jerry Lanchbury, Myriad’s chief scientific officer.”
• Genomic Prediction launched their Expanded Pre-implantation Genomic Testing in September. It covers many single gene disorders and uses polygenic scoring for complex disorders (Type 1 Diabetes, Type 2 Diabetes, Coronary Artery Disease, Atrial Fibrillation, Breast Cancer, Hypothyroidism, Mental Disability, Idiopathic Short Stature, Inflammatory Bowel Disease). They are working on height. The cost will be $400 per embryo (source). From the same source, the CSO, who has Type 1 Diabetes, explains that the company wants to move on to genome editing “If his own parents had that option, “they could have potentially edited out my diabetes and it would have been a cure,” he said. “I would have been here without diabetes.” The irony is, if his parents had access to their PGD product, he would probably never have been born.
• In a striking example of the misuse of genetics, an image of white supremacists chugging milk has been doing the rounds. The act goes with the message that those who can’t digest milk should “go home”. Those of caucasian ancestry, and inconveniently for the supremacists, also those of East-African ancestry, tend to have the ability to digest lactose. The report by Amy Harmon in the NYT states plainly some of the problems with addressing this: “Many geneticists at the top of their field say they do not have the ability to communicate to a general audience on such a complicated and fraught topic. Some suggest journalists might take up the task. Several declined to speak on the record for this article. And with much still unknown, some scientists worry that rebutting basic misconceptions without being able to provide definitive answers could do more harm than good. “There are often many layers of uncertainties in our findings,” said Anna Di Rienzo, a human genetics professor at the University of Chicago. “Being able to communicate that level of uncertainty to a public that often just sees things in black and white is very, very difficult.” The ASHG released a statement condemning this use of genetics, saying that concept of “racial purity” was scientifically meaningless.
• Robert Plomin’s book Blueprint, which is newly released in the UK, is already stirring controversy. One commentator notes “Yet in the end with Blueprint, there exists a risk that readers end up impressed by Plomin’s account of his science without being aware of the racial and social implications of his theory. And in the context of a resurgent right wing across the world looking for “scientific” reasons to elevate race in public policy, this seems profoundly irresponsible.”

 

Science

• The UK biobank has released its data on 500,000 individuals. Each individual is genotyped, and will have their health outcomes collected prospectively. MRI data for 100,000 of the individuals should be available by 2020. “UK Biobank is an open-access resource that encourages researchers from around the world, including those from the academic, charity, public and commercial sectors, to access the data for any health-related research that is in the public interest.”
• Successful in utero gene-editing of mice. The researchers introduced to the mice what is probably the most famous “good news” gene variant, a loss of function in PCSK9, which lead to lower LDL-C and coronary heart disease incidence.
• Chinese scientists report on the birth of mice with two mums (“bi-maternal”) and with two dads (“bi-paternal”). Some of the bi-materna pups survived to adulthood and were fertile. Some of the bi-paternal mice survived birth, but died shortly afterwards. The researchers had to deal with the fact that a lot of the genome is imprinted in a sex specific fashion.
• Unpublished results were presented at ASHG on ~37,000 exomes of those with Autism Spectrum Disorder. They identify ~100 genes related to the condition, but a surprise was that a large proportion were more closely associated to intellectual disability or developmental delay.
• From ASHG: Preliminary results of 30,000 trios (patient and parents) of patients with developmental delay has found genetic causes in about a quarter of participants, linking 302 genes to the condition.
• In further results reported ahead of publication at ASHG, in a dataset of ~490,000 people researchers identified 4 variants (2 just in males) that are associated with having had same-sex partners, a trait that is about ~40% heritable. “We found that variants predisposing to non-heterosexual behavior are, among heterosexuals, positively associated with having more self-reported lifetime sexual partners and, in heterosexual males, with being judged more to be physically attractive. This is consistent with the hypothesis that genetic variants predisposing to non-heterosexual behavior confer a mating advantage to heterosexual carriers.”
• Continuing the story of the widely covered Educational Achievement polygenic score which I covered in my last post

• Economic researchers applied the score in combination with economic data (working paper). The results? As one of the authors reported to the Post, “If you don’t have the family resources, even the bright kids — the kids who are naturally gifted — are going to have to face uphill battles.”
• A twin study based on UK individuals on the genetics of university success produced heritability estimates for: entrance exam achievement (57%), the choice to study at university (51%), the quality of university attended (57%) and achievement at university (46%). (Numbers are the proportion of variance in the trait explained by inherited factors). The Educational Achievement polygenic score, which captures 11-13% of variance in number of years of education, captured 4%, 5%, 2%, 7% of this variation respectively.

• This was a piece I started to read not expecting a connection to genomics: the story of the placebo effect, and attempts to unpick its biochemistry. Researchers formed a hypothesis that variation that affected the levels of COMT, an enzyme that helps determine levels of dopamine and its relatives. They have indeed found evidence of this. The suggestion is that somehow the caring involved in a patient-physician interaction stimulates the same biochemical pathway that many drugs use. This suggests that the blinded placebo trial may be inappropriate: “the placebo effect is not just some constant to be subtracted from the drug effect but an intrinsic part of a complex interaction among genes, drugs and mind.” And of course “The [pharma]industry would be delighted if it were able to identify placebo responders — say, by their genome — and exclude them from clinical trials.” Thinking beyond trials to the administration of medicine, “Should medical rituals be doled out according to genotype, with warmth and caring withheld in order to clear the way for the drugs?”
• I had previously missed this: a European initiative to overcome data silos and privacy concerns to assemble a million genomes by 2022.
• A new study from Calico and Ancestry.com estimates the heritability of lifespan to be under 10%. It was previously believed to be higher, but they think that this was inflated due to the effects of assortative mating.
• The largest ever genetic study from China of over 140,000 Chinese individuals has been reported. It was based on blood processed for Non-invasive prenatal testing of pregnant women.
• The Garvan Institute in Australia has sequenced the genomes of 4000 healthy elderly individuals. I remember when 4000 sounded enormous…
• In more new datasets, about 2000 genomes of individuals from rural Uganda, and genotype results from thousands of other across Africa. This is beginning to help us unpick the early starts of human population structure.
• Gout was previously thought to be associated with diet. But a new study of ~17,000 individuals finds that the effects of diet are very minimal, whereas genetics plays a large role, explaining ~24% of the variance.
• A new version of CRISPR, CRISPR-GO can alter the genome’s organization.

 

Applications

• In a major consolidation in the sequencing space, Illumina is buying PacBio, allowing the market leader access to long read technology.
• An analysis of variant classification changes in Myriad’s reports over the last ten years found that 25% of reports had variants of uncertain significance that had since been re-classified. A full 90% of these variants were reclassified as likely benign/benign. In its coverage of this, the NYT stresses that most labs do not have a good process in place for what to do when a variant is re-classified.
• Should tests for Fragile-X and SMA be added to the newborn screening panel? A pilot is under way in North Carolina.
• 23andMe’s FDA approval for displaying health related genetic information grow further, now extending to some pharmacogneomic variants. Key to the approval was data submitted to show user comprehension.
• A study that shows that “about 60% of the searches for individuals of European descent will result in a third-cousin or closer match, which theoretically allows their identification using demographic identifiers”. The search was based on data in te MyHeritage database, which has about 1.28 million users at the time. The first author of that paper, Yaniv Erlich, has been tweeting to keep track of cold cases solved via familial DNA searching. Count as of Nov 3 is 22.
• A pilot study of expanded carrier screening of over 10,000 people in China, funded by BGI. The authors conclude “Our data demonstrate the feasibility of ECS, and provide evidence that ECS is a promising alternative to traditional one-condition screening strategies.” Compare to this call for the implementation of this testing throughout China, where the first authors are from the Research Institute for Birth Defect Prevention and Control.
• It’s easy to bash precision medicine, but there are some success stories. Here’s a story of a N-of-1 drug for a girl with Batten disease, which is fatal. The drug is an antisense oligonucleotide, the same class of drugs as nusinersen/Spinraza for spinal muscular atrophy (SMA)
• The BabySeq and MedSeq projects, with both sequence genomes of healthy individuals, reported at ASHG that they had found “unanticipated risk variants” in 16 of 110 adults (14.5%) and 18 of 159 infants (11.3%). Upon follow up, some of these were found to indeed have the diseases indicated. These numbers were higher than they were expected.

 

Regulation

• A bill to recognise certified genetic counsellors as health providers has been introduced to the US house of representatives. If passed, counselling services could be covered by Medicare..
• In Australia, life insurers will no longer require the disclosure of adverse genetic testing results.
• A comparison of data sharing regulations in seven countries. Part of the Global Alliance for Global Health, the work was seen as a prerequisite to build upon: “The future of genomic data sharing depends on a creative yet responsible interpretation of existing legal norms in order to ensure that we truly respect the human right of everyone to benefit from scientific progress and its applications,” said Knoppers.
• A meta-analyses of studies investigating people’s fears of genetic privacy found over 50 studies, found “The picture of genetic privacy that emerges from this systematic literature review is complex and riddled with gaps.” I found this conversation with Jen King, director of consumer privacy at the Center for Internet and Society at Stanford Law School, referencing results that people tend not to think of their genetic data as any more personal than their google searches. This motivates contributing data to research, but individuals can think differently again when they are walked through potential implications — e.g. that drug companies can sell any drugs produced at whatever price the market will bear.
• A loophole involving the collection of DNA from minors has been closed with a bill in California. What most interested me about this is the close involvement of the Electronic Frontier Foundation, which makes sense as DNA data is increasingly another tool of surveillance.