The annual American Society of Human Genetics conference happened in October in Orlando, ensuring that there was plenty of research news. The N of some studies is truly outstanding, with >10,000 seeming normal. Meanwhile, self-CRISPRing has definitely started, the role of multiple driver mutations in a given tumor is increasingly clear, and an eclectic mix of stories make it into a section I decided to call “Social Backdrop”.
A moment to stop and reflect that October 24th marked the 20th anniversary of the screening of GATTACA. This is a film that I have seen raised by genetics professionals several times in the context of concern about the future we are headed to.
- A study of ~2800 probands with congenital heart disease, most of whose parents were also available for analysis, was able to explain 1.8% of the cases with recessive inheritance and 8% of cases with de novo mutations. These numbers are not large, despite a study of this size, pointing either to the role of even rarer variants, or the role of non-genetic factors.
- Up to 25% of longevity is believed to be genetic. Three loci had previously been associated with lifespan (near APOE, FOXO3A and CHRNA3/5). Combining genetic info from 600,000+ individuals with the lifespans of their parents allowed a team to use Mendelian Randomization to investigate the role of both disease and lifestyle factors on lifespan, adding HLA-DQA1/DRB1 and LPA to the list of genomic regions, and the usual suspects to lifestyle factors.
- A study of 30,000 pairs of twins found the concordance rate of schizophrenia is 33% in identical twins and 7% in non-identical twins. From this the authors backed out a heritability of 79% for schizophrenia.
- Report that low mitochondrial copy number is a risk factor for heart disease (CVD): “among 21 870 participants from 3 cohort studies, the hazard ratio for incident CVD associated with a 1-SD decrease in mitochondrial DNA copy number was 1.23”
- A study of human skin pigmentation has shown that some of the variants associated with lighter skin are older than their darker counterparts. Also evidence that the same variant has differing effects depending on the genetic background. From the author: “The study really discredits the idea of a biological construct of race. There are no discrete boundaries between groups that are consistent with biological markers.”
- In a GWAS study of over 300,000 people, researchers found that the vast majority of risk variants for asthma, hay-fever and eczema are in common across the diseases.
- Polygenic risk models are on the rise, including a clinical test for likelihood of developing Alzheimer’s.
- Science has a write-up of Geisinger’s My Code project, which has already performed clinical exome sequencing of nearly 100,000 of their patients. They are currently focused on reporting back results in ~75 clinically actionable genes, and about 3.5% of people will find out that they have an actionable deleterious variant.
- The Tech Review covers the existence of a new start-up, Genomic Prediction, which aims to predict a pre-implantation embryos’s genetic risk for complex diseases. The founders have been involved in studies such as the Chinese study that has attempted to pin down the genetics underlying mathematical ability.
- The new York Times has a nice write up on endogenous viruses, including theories around why viral proteins tend to get expressed in the early embryo.
- A pilot study for MilSeq — which sequences US air force personnel – is underway. There are fears that genomics could be “double edged sword” in the military, where physical conditions make predisposition testing potentially life saving, but where commanders have some degree of latitude in using disease predisposition to determine operational readiness.
- A biohacker in California has been self-CRISPRing, and believes he is the first to do so. His target was Myostatin, that when knocked out leads to more muscle mass.
- A majority of genetics professionals are in favor of both somatic and germline gene therapy.
- Promising results for use of nanoparticles to deliver CRISPR.
- Unlike for inherited traits (germline), which evolve by negative selection, tumors evolve by positive selection. This is one of the findings from the analysis of >7000 tumors published in Cell. Half of the coding driver mutations were located outside known cancer genes. “On average, tumors carry ∼4 coding substitutions under positive selection, ranging from <1/tumor in thyroid and testicular cancers to >10/tumor in endometrial and colorectal cancers”
- A case-control study of breast cancer susceptibility with an N > 200,000 finds several new loci involved, including different ones for hormone receptor negative versus positive forms of the disease. They also demonstrated that the germline variants overlap those that are acquired in tumors.
- p53 is a master cancer regulator, but its mechanisms of action have been elusive. A team looking at pancreatic cancer development in mice found a mutant of p53 that helped suppress tumors more than wild-type. This lead them to one pathway that gives a mechanism of action (via the p53-Ptpn14-Yap pathway).
- The majority of late stage lung cancer patients with EGFR mutations harbor additional driver mutations.
- Caris Life Sciences is suing Foundation Medicine over patent infringement of its IP covering use of molecular profiling for treatment options.
- Russia has accused the US of collecting DNA of its citizens in order to develop biological weapons targeted at their genetic make-up.
- Anecdotal reports that repeal of the ACA is making people more reluctant to learn their genetic risks.
- In 2015, Kuwait passed a law which required all citizens and visitors to submit samples of their DNA. The law has been successfully challenged on the basis that it violates the constitution’s guarantee of personal liberty.
- There have been murmerings about use of blockchain technologies to protect genetic information. Now Garvan have partnered with a blockchain company to explore possibilities.
- The World Anti Doping Agency, which pro-actively banned any form of gene therapy for performance enhancement back in 2003, clarified that attempts to use CRISPR for performance enhancement were strictly banned. Athlete use for therapy would be okay, but only to return to “normal” levels.
- The software used by New York in forensic testing between 2011 and 2016 has been publicly released, and it doesn’t look sturdy.
- Fortune magazine raises concerns that the rich will be paying for designer babies before too long.
- The BabySeq project has some data points over concerns related to privacy – 90% of parents approached did not opt in to the study.
- The FDA may have just made it easier for direct to consumer genetic tests to hit the market. In s statement, they said “If and when finalized, manufacturers of these types of tests would have to come to FDA for a one-time review to ensure that they meet the FDA’s requirements, after which they may enter the market with new GHR tests without further review.”
- A write-up of the rise, fall and rise again of 23andMe, with a focus on its tumultuous relationship with the FDA.