Two truly ginormous releases of data

• The Biobank, ~500,000 individuals with extensive phenotypes, has released the first ~50,000 whole exome sequences (complementing the Chip data that has been around for longer).
• The National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine (TOPMed) program has a data set of ~50,000 whole genomes (of a planned 145,000). An exciting fact about this data set is that ~30% are from individuals with African ancestry. The individuals are extensively phenotyped. Much of the genetic data (I’m unclear how much) is available on dbGap.

The size of NGS data has truly exploded. Here’s hoping that this sort of size dataset will allow us to peel back the curtain on the clinical relevance of rare variation.

Controversy — mostly China

• More on CRISPRed babies
  • Inadvertent cognitive enhancement? – The edit introduced into the CCR5 gene in Lulu and Nana is associated with increased smartness in mice, and faster recovery from stroke and higher school success in humans.
  • In further twists, perhaps state agencies in China knew more than they were letting on about He’s experiments, which are now very much being portrayed as those of a “rogue actor”
  • Approval of future trials involving gene-editing would be handled by China’s national cabinet, the State Council, under new proposals by Beijing to further regulate gene-editing.
• The Times covers the story of Beijing’s genetic surveillance of the Uighur population. Thermo Fisher, whose instruments and expertise have been used as part of the program,  have stopped sales and services of instruments to be used in Xinjiang province, stating conflict with their ethics code. Bioethicist Dr Caplan was quoted as saying “Honestly, there’s been a kind of naïveté on the part of American scientists presuming that other people will follow the same rules and standards wherever they come from.”
• “Talent testing” for toddlers is a thing in China, e.g. CBT Gene in Shenzhen, whose genetic tests cover  “musical, mathematical, and reading abilities; physical talents; attributes like shyness, introversion, extroversion, and memory.”

Science

• A massive GWAS for depression covering 100,000s of cases and controls has identified new loci. The resulting polygenic score explained 1.5-3.2% of the variance (for a condition with an estimated heritability of 30-40%), depending on target cohort.
• The Human Reference Genome is increasingly under attack. Its problems have been obvious for a long time, but attention is now starting to really focus on them. See this piece giving the historical context from STAT. And a recent paper probing structural variant that really highlights the issue — they found 60MB of sequence not mappable to the reference genome.
• Some conditions affect different ancestral populations to different degrees. Asthma affects those of African ancestry disproportionately, but has been understudied in that population. A new study looking at African-admixed asthma cases and controls identifies “two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.”
• An impressive new technology for looking at genome wide gene expression levels at high spatial resolution, Slide-seq.
• A report on the heritability of child maltreatment; “our findings suggest that genetic pathways play a significant role in perpetrating emotional abuse, while physical abuse and emotional neglect are transmitted primarily through common environmental factors.”
• A gain of function variant in the gene LRRK2 is known to significantly increase the chances of an individual developing Parkinsons. Could inhibition of the same gene be therapeutic? The authors looked in large data sets (GnomAD and 23andMe) to find individuals who had only one working copy of the gene, and found no ill effects, suggesting that inhibition could indeed be a safe strategy to pursue.
• We’re used to seeing mitochondrial DNA represented as small circles, but new long read data shows that this is an oversimplification: “Our data demonstrate that representations of plant mitochondrial DNA as simple, genome-sized circular molecules are not accurate descriptions of their true nature and that in reality plant mitochondrial DNA is a complex, dynamic mixture of forms.”
• Dealing with the effects of variants on multiple transcripts has always been a problem for genome annotation. Here is a new tool from the GnomAD team that will do expression based annotation (it takes an isoform expression file as an input).

Applications

• 23andMe have launched a Type 2 Diabetes score. Using a freshly developed polygenic score based on their 2.5 million customers, it adjusts the score based on ethnicity and age to give not just a relative odds, but a percentage chance of developing the condition in the next x years. I was unable to confirm this as it doesn’t work on my report — perhaps because it only works for the latest chip.
• The PeopleSeq consortium has partnered with the major projects that offer genome sequencing to healthy individuals (“predispositional screening”). They send out surveys to participants before and after screening. In their first published results covering several hundred people, they found that while most individuals discussed the results with their doctor, only 13.5% made an appointment specifically for that purpose. About 40% reported that they learnt something new about their health, but fewer than 10% made any changes. More than half were disappointed that they did not receive more actionable information. One message the authors want us to take home: patients felt empowered rather than distressed by their results.
• A group of 8 institutions wants to see whole genome sequencing in the clinic, and have formed the Medical Genome Initiative to help establish best practices etc to make this happen.

Regulation

• Following the case of the rape (and subsequent pregnancy) of a woman in an intermediate care facility, Arizona is considering a law to make it mandatory for people who work with the intellectually disabled in these facilities to provide DNA samples first. This is a watered down version of the proposal that started with mandating that anybody who had to be fingerprinted as part of their work would have to give a sample.
• Meanwhile, Kansas are considering a bill that will see new DNA samples matched to not just open cases but also closed cases. This would help in cases where the wrong person was convicted for a crime.
• A family’s story that highlights the difficulties with anonymous sperm donors

And in other interesting things, here is a nice write-up of the extent to which humans are innately violent — tracing the debates, and pointing to the question, do we need an answer to this question? Also, whether our views on this question affect our beliefs about peace-keeping efforts.