Flipping DNA switches

The recently published SSGAC study (Nature News) found 74 genome-wide significant hits related to educational attainment, using a discovery sample of ~300k individuals. The UK Biobank sample of ~110k individuals was used as a replication check of the results. If both samples are combined as a discovery sample 162 SNPs are identified at genome-wide significance. …

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74 SNP hits from SSGAC GWAS

The SSGAC discovery of 74 SNP hits on educational attainment (EA) is finally published in Nature. Nature News article. EA was used in order to assemble as large a sample as possible (~300k individuals). Specific cognitive scores are only available for a much smaller number of individuals. But SNPs associated with EA are likely to …

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This is for PZ Myers

Scott Alexander (Slate Star Codex), Garrett Jones (Hive Mind), and Razib Khan (GNXP) alerted me (via Twitter) of this post by PZ Myers. Myers is both confused and insulting in his blog post, but I’ll refrain from ad hominem attacks, and just focus on the science. Myers seems to think that humans with much better …

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Genetic ancestry and brain morphology

Population structure — i.e., distribution of gene variants by ancestral group — is reflected in brain morphology, as measured using MRI. Brain morphology measurements can be used to predict ancestry. Strictly speaking, the data only show correlation, not genetic causation, but the most plausible interpretation is that genetic differences are causing morphological differences. One could …

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Can Genius Be Genetically Engineered?

See you at the 92nd Street Y tomorrow (Thu, Mar 10, 2016, 8:15 pm)! With rapid advances in genome sequencing, genetic analysis and precision gene editing, it’s becoming ever more likely that embryo selection and genetic engineering could be used to optimize the intelligence of our future children. Although the complexities of genetics, the brain …

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Improved CRISPR–Cas9: Safe and Effective?

Two groups (Zhang lab at MIT and Joung lab at Harvard) announce improved “engineered” Cas9 variants with reduced off-target editing rates while maintaining on-target effectiveness. I had heard rumors about this but now the papers are out. See CRISPR: Safe and Effective? Nature commentary Genome Editing: The domestication of Cas9. High-fidelity CRISPR–Cas9 nucleases with no …

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Cognitive Genomics Interview

This is a discussion with Cambridge University PhD candidate Daphne Martschenko. Topics covered include: genetics of cognition, group differences, genetic engineering. The NYC roundtable on genius she mentions is here. Blog readers may also be interested in this event at the 92nd Street Y (Thu, Mar 10, 2016, 8:15 pm, Location: Lexington Avenue at 92nd …

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In vivo gene editing with CRISPR

Safe and Effective soon for humans? In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophyin vi Science DOI: 10.1126/science.aad5143 Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore …

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GCTA, Missing Heritability, and All That

Bioinformaticist E. Stovner asked about a recent PNAS paper which is critical of GCTA. My comments are below. It’s a shame that we don’t have a better online platform (e.g., like Quora or StackOverflow) for discussing scientific papers. This would allow the authors of a paper to communicate directly with interested readers, immediately after the paper …

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Nativity 2050

And the angel said unto them, Fear not: for, behold, I bring you good tidings of great joy, which shall be to all people. Mary was born in the twenties, when the tests were new and still primitive. Her mother had frozen a dozen eggs, from which came Mary and her sister Elizabeth. Mary had …

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Fear Not!

For relentless technological advance, powered by high g researchers, venture capitalists, capital markets, and government investment in basic research, continues to deliver a cornucopia of benefits to the average joe. (Note, however, that Moore’s Law itself has stalled out recently …) Tweet

Largest repositories of genomic data

This list of the largest repositories of genetic data appeared in the 25 September 2015 issue of Science. Note that the quality and extent of phenotyping varies significantly. 23andME SIZE: >1 million GENETIC DATA: SNPs This popular personal genomics company now hopes to apply its data to drug discovery (see main story, p. 1472). ANCESTRY.COM …

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No genomic dark matter

Let me put it very simply: there is NO genomic “dark matter” or “missing heritability” — it’s merely a matter of sample size (statistical power) to identify the specific variants that account for the total expected heritability. The paper below (see also HaploSNPs and missing heritability) suggests that essentially all of the expected heritability can …

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HaploSNPs and missing heritability

By constructing haplotypes using adjacent SNPs the authors arrive at a superior set of genetic variables with which to compute genetic similarity. These haplotypes tag rare variants and seem to recover a significant chunk of heritability not accounted for by common SNPs. See also ref 32: Yang, J. et al. Estimation of genetic variance from …

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Technically Sweet

Regular readers will know that I’ve been interested in the so-called Teller-Ulam mechanism used in thermonuclear bombs. Recently I read Kenneth Ford‘s memoir Building the H Bomb: A Personal History. Ford was a student of John Wheeler, who brought him to Los Alamos to work on the H-bomb project. This led me to look again …

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Sparsity estimates for complex traits

Note the estimate of few to ten thousand causal SNP variants, consistent with my estimates for height and cognitive ability. Sparsity (number of causal variants), along with heritability, determines the amount of data necessary to “solve” a specific trait. See Genetic architecture and predictive modeling of quantitative traits. T1D looks like it could be cracked …

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Fifty years of twin studies

The most interesting aspect of these results is that for many traits there is no detectable non-additivity. That is, gene-gene interactions seem to be insignificant, and a simple linear genetic architecture is consistent with the results. Meta-analysis of the heritability of human traits based on fifty years of twin studies Nature Genetics (2015) doi:10.1038/ng.3285 Despite …

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DNA Dreams at Harvard

This is a panel discussion of the documentary film DNA Dreams (see below), about BGI and its Cognitive Genomics Lab. DNA DREAMS Moderator: Dr. Evelynn Hammonds, Director of the Project on Race & Gender in Science & Medicine, Hutchins Center for African & African American Research/Barbara Gutmann Rosenkrantz Professor of the History of Science Panelists include: (L …

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CRISPR edits in human zygotes

Results such as these had been the subject of rumors for some time. Also covered in Nature News. It is very early days for this technology — the off-target rate can probably be reduced significantly using better methods. But in the near term, safety and efficacy issues make PGD a better technique for improving human …

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Gene drive

IIUC, there is a self-referential (“auto-catalyzing”) aspect to this method which is very interesting. The Cas9 gene (payload) also encodes the guide RNA (target) information, which determines the location of the DNA cut. Needless to say, this is a very powerful and potentially dangerous technology. Enrico Fermi (speaking about atomic weapons): Once basic knowledge is …

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The Fourth Law of Behavior Genetics?

I believe the law stated below almost follows from the observation that humans brains are complex machines: hence the DNA blueprint has many components, and variance is spread over these components  :^) However, note the evidence for discrete genetic modules of large effect in other species: Discrete genetic modules can control complex behavior (burrowing behavior in …

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Garbage, Junk, and non-coding DNA

About 1% of the genome codes for actual proteins: these regions are the ~20k or so “genes” that receive most of the attention. (Usage of the term “gene” seems to be somewhat inconsistent, sometimes meaning “unit of heredity” or “coding region” or “functional region” …) There’s certainly much more biologically important information in the genome …

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Funding the LTEE—past, present, and future: Questions from Jeremy Fox about the LTEE, part 4

This is the 4th installment in my responses to Jeremy Fox’s questions about the long-term evolution experiment (LTEE) with E. coli. This response addresses his 5th and 6th questions, which are copied below.  ~~~~~ How have you maintained funding for the LTEE over the years, and how hard has it been? The difficulty of sustaining funding for long term work …

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Multiallelic copy number variation

These new results probe surprisingly large variation in copy number (duplicated genomic segments) and its impact on gene expression. Earlier posts involving CNVs. Large multiallelic copy number variations in humans Nature Genetics (2015) doi:10.1038/ng.3200 Thousands of genomic segments appear to be present in widely varying copy numbers in different human genomes. We developed ways to …

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More GWAS hits for cognitive ability

More genome-wide significant associations between individual SNPs and cognitive ability from a sample of 50k individuals. See also First GWAS hits for cognitive ability. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949) Nature Molecular Psychiatry advance online publication 3 February 2015 doi: 10.1038/mp.2014.188 General …

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Analogies between Analogies

As reported by Stan Ulam in Adventures of a Mathematician: “A mathematician is a person who can find analogies between theorems; a better mathematician is one who can see analogies between proofs and the best mathematician can notice analogies between theories. One can imagine that the ultimate mathematician is one who can see analogies between …

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CRISPR patent fight

Earlier CRISPR posts. MSU symposium with video (Patrick Hsu, one of the speakers (no relation), is from the Zhang lab). Technology Review: Discovery of the Century? There’s a bitter fight over the patents for CRISPR, a breakthrough new form of DNA editing. … In April of this year, Zhang and the Broad won the first of several sweeping patents that cover …

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de novo mutations and autism

These results suggest that autism spectrum disorder (ASD) in high functioning males may be a different condition than ASD in low-IQ males and females. They also suggest many gene targets in which small “nicks” could result in lower IQ. I believe that at least part of “normal” population variation in IQ is due to effects …

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Adaptive evolution and non-coding regions

This morning I attended an excellent talk: Adaptive Evolution of Gene Expression (see paper and video below), by Hunter Fraser of Stanford. His results support the hypothesis that non-coding regions of the genome play at least as large a role in evolution and heritable variation as protein coding genes. From an information-theoretic perspective, it seems …

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