Smart stats make use of large-scale health insurance claims

Repurposing large health insurance claims data to estimate genetic and environmental contributions in 560 phenotypes

We analysed a large health insurance dataset to assess the genetic and environmental contributions of 560 disease-related phenotypes in 56,396 twin pairs and 724,513 sibling pairs out of 44,859,462 individuals that live in the United States. We estimated the contribution of environmental risk factors (socioeconomic status (SES), air pollution and climate) in each phenotype. Mean heritability (h2 = 0.311) and shared environmental variance (c2 = 0.088) were higher than variance attributed to specific environmental factors such as zip-code-level SES (varSES = 0.002), daily air quality (varAQI = 0.0004), and average temperature (vartemp = 0.001) overall, as well as for individual phenotypes. We found significant heritability and shared environment for a number of comorbidities (h2 = 0.433, c2 = 0.241) and average monthly cost (h2 = 0.290, c2 = 0.302). All results are available using our Claims Analysis of Twin Correlation and Heritability (CaTCH) web application.

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Extended genetic alphabet covered in New York Times

DNA Gets a New — and Bigger — Genetic Alphabet

DNA is spelled out with four letters, or bases. Researchers have now built a system with eight. It may hold clues to the potential for life elsewhere in the universe and could also expand our capacity to store digital data on Earth.

In 1985, the chemist Steven A. Benner sat down with some colleagues and a notebook and sketched out a way to expand the alphabet of DNA. He has been trying to make those sketches real ever since.

On Thursday, Dr. Benner and a team of scientists reported success: in a paper, published in Science, they said they have in effect doubled the genetic alphabet.

Natural DNA is spelled out with four different letters known as bases — A, C, G and T. Dr. Benner and his colleagues have built DNA with eight bases — four natural, and four unnatural. They named their new system Hachimoji DNA (hachi is Japanese for eight, moji for letter).

Crafting the four new bases that don't exist in nature was a chemical tour-de-force. They fit neatly into DNA’s double helix, and enzymes can read them as easily as natural bases, in order to make molecules.

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Autism GWAS finds common risk variants

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci.

Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.

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Insomnia GWAS with 1.3 million individuals yields results

Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways

Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited.

Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and gain insight into the pathways, tissue and cell types involved in insomnia complaints.

We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping. The meta-analysis explained 2.6% of the variance. We show gene set enrichments for the axonal part of neurons, cortical and subcortical tissues, and specific cell types, including striatal, hypothalamic, and claustrum neurons. We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits. Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume. Our findings highlight key brain areas and cell types implicated in insomnia, and provide new treatment targets.

Crispr Therapeutics AG has treated its first human

Crispr Infuses First Human in Landmark Gene-Editing Study

Crispr Therapeutics AG  shares surged after the company said it has treated the first human with the same genetic technology that shares its name in an early-stage study.

Crispr Therapeutics and partner Vertex Pharmaceuticals Inc. said on Monday morning that the first patient in a trial using CTX001, a therapy created using Crispr technology, as a treatment for the rare blood disease, beta thalassemia, received the one-time medicine. The pair also announced the enrollment of the first patient has started in a parallel study for the medicine in sickle-cell disease with the first dosing on track for mid-year.

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New DNA repair mechanism identified

Novel DNA repair mechanism preserves genome integrity

"I'm just astounded," said Cortez, Ingram Professor of Cancer Research and professor of Biochemistry. The investigators, led by postdoctoral fellow Kareem Mohni, Ph.D., have discovered a new DNA repair mechanism.

"DNA repair is a very mature field. The Nobel Prize was given a few years ago to three scientists who studied DNA repair in the 1970s and 80s," Cortez said.

"People are still very interested in DNA repair, and there are important questions that we're asking, but the idea of finding a whole new repair mechanism … nobody would have thought this is possible."

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CRISPR Gene Editing advances

Gene Editing is trickier THAN expected—BUT fixes are in sight

Of all the big, world-remaking bets on the genome-editing tool known as Crispr, perhaps none is more tantalizing than its potential to edit some of humanity’s worst diseases right out of the history books. Just this week, Crispr Therapeutics announced it had begun treating patients with an inherited blood disorder called beta thalassemia, in the Western drug industry’s first test of the technology for genetic disease. But despite the progress, there remain a host of unknowns standing in the way of Crispr-based medicines going mainstream, chief among them safety.

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World Health Organization might make some human genome editing rules

Human genome editing is here – now we have to decide who is in charge

The World Health Organization (WHO) will convene a meeting this month to develop global standards of governance for human genome editing. This is a welcome move. Although the committee has no powers to enforce compliance – it is still a matter for individual nations to decide on regulations, with China reportedly updating its rules earlier this week – the WHO committee’s recommendations will be influential and far-reaching in their ambition. But I hope committee members will bear a few points in mind in their discussions.

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Four new bases available for synthetic biology (original article)

Hachimoji DNA and RNA: A genetic system with eight building blocks

Expanding the genetic code

DNA and RNA are naturally composed of four nucleotide bases that form hydrogen bonds in order to pair. Hoshika et al. added an additional four synthetic nucleotides to produce an eight-letter genetic code and generate so-called hachimoji DNA. Coupled with an engineered T7 RNA polymerase, this expanded DNA alphabet could be transcribed into RNA. Thus, new forms of DNA that add information density to genetic biopolymers can be generated that may be useful for future synthetic biological applications.

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CRISPR quality improvement tested

CRISPR Base Editor Takes Diagnostic and Remedial Exams

Whether a CRISPR-based editing tool makes the grade or needs remedial work isn’t clear until it is subjected to testing, thorough and systematic testing. Consequently, scientists based at South Korea’s Institute for Basic Science (IBS) are administering the CRISPR equivalent of standardized tests. Rather than present CRISPR tools with a #2 pencil and a fill-in-the-oval sheet, the scientists provide different guide RNAs. Then the scientists use genome sequencing to check for errors such as off-target effects.

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What will human cloning be like, when we eventually start doing it...

#Science #Biology #Medicine #HumanCloning #Future

It had looked impossible, but, in the end it was surprisingly easy. So, though few knew of their creation at the time, the first human clones were born in 2020 in Taiwan. Now, as those clones celebrate their 30th C-days, it seems a good moment to review the history of cloning…

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CRISPR off-target errors

A CRISPR spin-off causes unintended typos in DNA

Even the best editor sometimes introduces typos. That’s true whether the editor is human or a version of the much-heralded gene-editing tool CRISPR.

One type of CRISPR gene editor that changes individual DNA bases, rather than cutting DNA, introduces more unwanted mutations than expected in mouse embryos and rice plants, researchers report. Those mistakes occurred in places where the tool wasn’t supposed to make changes. Another tested base editor, however, didn’t make the undesirable edits. The results were described in two studies published online February 28 in Science.

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CRISPR ups corn yields

Scientists Use CRISPR on Edit-Resistant Corn to Boost Yields

Scientists have used pollen carrying CRISPR/Cas9 to genetically edit hard-to-edit crops like corn, opening the door to new ways to boost important crop yields.

CRISPR/Cas9 Used on Edit-Resistant Corn Crops 

Scientists at the North Carolina-based agricultural firm Syngenta have discovered a novel way to use CRISP/cas9 gene-editing techniques on important varieties of corn that have proven especially resistant to the process, according to Science magazine.

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(CAR)-T treatment for Lupus looks promising

Genetically engineered immune cells wipe out lupus in mice

Lupus can be a stubborn disease to treat. Although many struck by the autoimmune condition live relatively normal lives, some suffer from kidney failure, blood clots, and other complications that can be deadly. Now, scientists have found that a novel treatment that wipes out the immune system’s B cells cures mice of the condition. Though the work is preliminary, it has excited researchers because it uses a therapy already approved for people with blood cancer.

The strategy is known as chimeric antigen receptor (CAR)-T therapy. 

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More populations need to be sampled from the whole human family tree

Lack of diversity hinders genetic studies. We can change that

As a geneticist, I feel fortunate to live in the post-genomic era. The sequencing of the human genome has made it possible to make advances in understanding human genetics at an unprecedented pace. Genetic research is changing our understanding of early human migration and offering tantalizing insights into human biology. I have high hopes that we will be able to use these insights to better prevent, treat, and potentially cure diseases.

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RNA-seq advances aim to get it all

Taming the RNA Zoo While Saving Rare Transcripts

The lab is no wildlife park for RNA, but life sciences researchers can capture and display low-abundance, unstable, and otherwise vulnerable species

RNA analysis would do well to follow the example set by naturalists, scientists who patiently add new species to their catalogs while remembering that any catalog, however comprehensive, is of limited interest. What really matters, in botany or zoology or, more pertinently, RNA biology, is learning how species impact each other and fulfill their environmental roles.

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Potential of CAR T

Custom CAR T Cells Made to Order

Chimeric antigen receptor (CAR) T cells are about as cutting-edge as cancer care gets today. Having demonstrated the ability to eradicate tumor cells in up to 90% of patients with certain blood cancers, these engineered immune cells became the first class of gene therapy to win FDA approval in 2017—with Novartis’ Kymriah getting the nod in August, followed by Kite Therapeutics’ Yescarta in October.3 But Alexander Marson, MD, PhD, knows these sophisticated cells are capable of so much more.

Marson, an immunologist at the University of California at San Francisco, is exploring this potential by using the CRISPR-Cas9 system to introduce precisely targeted genome modifications. The idea is that by adding or deleting specific genomic sequences, one can make these cells more lethal for tumors but also safer for the patient. Marson’s team recently developed a platform called SLICE4—single-guide RNA (sgRNA) lentiviral infection with Cas9 protein electroporation—to perform diverse CRISPR modifications in many cells in parallel, in hopes of rapidly identifying changes that measurably improve CAR T-cell performance. “We’re pretty good at manufacturing the ‘hardware’ of gene edited cells, and we’re continuing to improve that,” says Marson. “The really interesting thing will be what genetic ‘software’ we can put into them.”

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China's CRISPR twins raise possibility of far off-target effects

China’s CRISPR twins might have had their brains inadvertently enhanced

New research suggests that a controversial gene-editing experiment to make children resistant to HIV may also have enhanced their ability to learn and form memories.

The brains of two genetically edited girls born in China last year may have been changed in ways that enhance cognition and memory, scientists say.

The twins, called Lulu and Nana, reportedly had their genes modified before birthby a Chinese scientific team using the new editing tool CRISPR. The goal was to make the girls immune to infection by HIV, the virus that causes AIDS.

Now, new research shows that the same alteration introduced into the girls’ DNA, deletion of a gene called CCR5, not only makes mice smarter but also improves human brain recovery after stroke, and could be linked to greater success in school.

CRISPR corrects Duchenne muscular dystrophy mutation

CRISPR-Cas9 corrects Duchenne muscular dystrophy exon 44 deletion mutations in mice and human cells

Abstract

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), which is characterized by lethal degeneration of cardiac and skeletal muscles. Mutations that delete exon 44 of the dystrophin gene represent one of the most common causes of DMD and can be corrected in ~12% of patients by editing surrounding exons, which restores the dystrophin open reading frame. Here, we present a simple and efficient strategy for correction of exon 44 deletion mutations by CRISPR-Cas9 gene editing in cardiomyocytes obtained from patient-derived induced pluripotent stem cells and in a new mouse model harboring the same deletion mutation. Using AAV9 encoding Cas9 and single guide RNAs, we also demonstrate the importance of the dosages of these gene editing components for optimal gene correction in vivo. Our findings represent a significant step toward possible clinical application of gene editing for correction of DMD.

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Massive family tree predicts life span is 16% heritable

Thirteen million degrees of Kevin Bacon: World’s largest family tree shines light on life span, who marries whom

Researchers have published what may be the validated largest family tree ever: a genealogy database stretching back 5 centuries that links 13 million people related by blood or marriage. The tree has already led to such insights as the link between genes and longevity and why our ancestors married whom they did. And researchers say that’s just a start.

“This study is an impressive and clever use of crowdsourcing data to address a number of interesting scientific questions,” says geneticist Peter Visscher of the University of Queensland in Brisbane, Australia, who was not involved with the work. The tree’s bigger promise, he and others say, could come if it were linked to health information to explore the role of genetics in diseases.

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