September 2018 gwern.net newsletter with links on genetics, human evolution, genetic engineering, LSD, and 1 book review.
2018-09-02–2021-01-09
finished
certainty: log
importance: 0
This is the September 2018 edition of the Gwern.net newsletter; previous, August 2018 (archives). This is a summary of the revision-history RSS feed, overlapping with my Changelog & /
Writings
Media
Links
Genetics:
Everything Is Heritable:
- “Genomic prediction of cognitive traits in childhood and adolescence”, Allegrini et al 2018 (More replication of Lee et 2018: 11% IQ/
16% education, boosted by genetic correlations—Figure 2: multi-trait boosted PGSes) - “A Polygenic Score for Higher Educational Attainment is Associated With Larger Brains”, Elliott et al 2018; “The genetic architecture of the human cerebral cortex”, Grasby et al 2018
- “The genetics of the mood disorder spectrum: GWASes of over 185,000 cases and 439,000 controls”, Coleman et al 2018
- “Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls”, Pettersson et al 2018 (population registry methods using siblings/
half-siblings continue to confirm twin study results) - “Machine Learning to Predict Osteoporotic Fracture Risk from Genotypes”, Forgetta et al 2018 (Lasso regression improves osteoporosis fracture prediction from 18% to 25%—the cost of using uninformative priors & stock linear regression)
- “Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia”, Bansal et al 2018 (The IQ/
schizophrenia relationship is clearly negative, for a variety of reasons, but some studies have found contrary results; Bansal et al 2018 may resolve this by finding heterogeneity within schizophrenia genetics—a BPD/ education (and thus potentially IQ) and a sub-schizophrenia trait. Something like this may also explain the puzzling IQ/ autism spectrum symptoms genetic correlation, pace Grove et al 2017…) - “Association Between Population Density and Genetic Risk for Schizophrenia”, Colodro-Conde et al 2018; “Genetic evidence of assortative mating in humans”, Robinson et al 2017 (confounding)
- “Evidence for gene-environment correlation in child feeding: Links between common genetic variation for BMI in children and parental feeding practices”, Selzam et al 2018
- “Analysis of the genetic basis of height in large Jewish nuclear families”, Zeevi et al 2018
- “Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression”, Strawbridge et al 2018
- “Common DNA Variants Accurately Rank an Individual of Extreme Height”, Sexton et al 2018 (media; Shawn Bradley, 7-foot-6, is +4.2SD above the mean on the GIANT height PGS)
- “Genomic prediction of cognitive traits in childhood and adolescence”, Allegrini et al 2018 (More replication of Lee et 2018: 11% IQ/
Recent Evolution:
- “Detecting past and ongoing natural selection among ethnically Tibetan women at high altitude in Nepal”, Jeong et al 2018 (more on the Tibetan altitude adaptations)
- “Combination of 247 Genome-Wide Association Studies Reveals High Cancer Risk as a Result of Evolutionary Adaptation”, Voskarides 2018
- “Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia”, Tucci et al 2018 (convergent evolution of hobbits & contemporary pygmies on Flores Island)
- “The palaeogenetics of cat dispersal in the ancient world”, Ottoni et al 2017 (media)
Engineering:
- “Generation of human oogonia from induced pluripotent stem cells in vitro”, Yamashiro et al 2018 (media: “The successful accomplishment of the same in human [cells] is just a matter of time. We’re not there yet, but this cannot be denied as a spectacular next step”; steps towards massive/
iterated embryo selection) - “A CRISPR-Cas9 gene drive targeting
doublesexcauses complete population suppression in caged Anopheles gambiae mosquitoes”, Kyrou et al 2018 (Lab demo of driving malaria mosquitoes to extinction with CRISPR gene drive and no evolved resistance) - “Large Genetic Change at Small Fitness Cost in Large Populations of Drosophila melanogaster Selected for Wind Tunnel Flight: Rethinking Fitness Surfaces”, Weber 1996; “Population Size and Long-term Selection”, Weber 2004; Walsh & Lynch 2018 discussion, graph of selection effects (The power of intense selection in large populations: Weber’s fruit-fly flying speed experiment was able to increase peak flying speed in a wind tunnel by >85x over 100 generations. See also the viral evolution lagoon which uses a similar mechanism to efficiently rank & select en masse.)
- “Accurate classification of BRCA1 variants with saturation genome editing”, Findlay et al 2018 (Creating 4000 BRCA mutations with CRISPR to measure their harmful effects)
- “Scientists Are Retooling Bacteria to Cure Disease” (Treating phenylketonuria (PKU) by ingesting bacteria genetically engineered to breakdown phenylalanine in the microbiome!)
- “Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose”, Li et al 2018
- “First test of in-body gene editing shows promise” (Gene editing people’s livers with zinc finger nucleases—unclear if it worked, but genetic editing keeps expanding.)
- “Generation of human oogonia from induced pluripotent stem cells in vitro”, Yamashiro et al 2018 (media: “The successful accomplishment of the same in human [cells] is just a matter of time. We’re not there yet, but this cannot be denied as a spectacular next step”; steps towards massive/
AI:
- Vast.ai (Vast.ai attempts to create a two-sided market for renting GPU servers from people with idle GPUs, substantially undercutting AWS/
GCP. Looks interesting—eg Nvidia 1070s at $2/ day.)
Statistics/
- “The prehistory of biology preprints: A forgotten experiment from the 1960s”, Cobb 2017 (Who killed preprints the first time? The commercial academic publishing cartel did. Copyright is why we can’t have nice things.)
- “Replication Failures Highlight Biases in Ecology and Evolution Science”
- “The cumulative effect of reporting and citation biases on the apparent efficacy of treatments: the case of depression”, de Vries et al 2018 (Figure 1: the flowchart of bias)
- “Two curious integrals and a graphic proof”, Schmid 2014 (perils of induction: the treacherous identities of the
2*cost(t)integral) - On Victorian vibrators and peer review: “A Failure of Academic Quality Control: The Technology of Orgasm”, Lieberman & Schatzberg 2018
- “Testing the ability of the ‘surprisingly popular’ method to predict NFL games”, Lee et al 2018 (An interesting opinion aggregation method—/
if you’re contrarian & you know it, clap your hands / Connected to the Bayesian truth serum for measuring/ forecasting.)
Politics/
- “Conspiracy As Governance”, Assange 2006
- Government crime labs are still dangerously incompetent at DNA testing: Butler et al 2018
Psychology/
- “Is Romantic Desire Predictable? Machine Learning Applied to Initial Romantic Attraction”, Joel et al 2018 (The heart has its reasons reason knows not…)
- “What Use is Intelligence?”, Hunt 2011 (Earl Hunt reviews some of the predictive power of IQ for education, careers, the military, and elsewhere.)
- “Dynamic Human Environmental Exposome Revealed by Longitudinal Personal Monitoring”, Jiang et al 2018 (media; towards the non-shared-environment)
- “California Teenagers Could Sleep Later Under School Start Bill”
- Hallucinogenic fish
Technology:
- “The Effect of Ad Blocking on User Engagement with the Web”, Miroglio et al 2018 (“we find statistically-significant increases in both active time spent in the browser (+28% over control) and the number of pages viewed (+15% over control)”—parallel results to my A/
B test of advertising effects and the Pandora experiment) - “SonarSnoop: Active Acoustic Side-Channel Attacks”, Cheng et al 2018
Economics:
“Examining Wikipedia With a Broader Lens: Quantifying the Value of Wikipedia’s Relationships with Other Large-Scale Online Communities”, Vincent et al 2018
Trial testimony transcripts from the trial of noted LSD manufacturer William Leonard Pickard, offering interesting insights into the business:
Philosophy:
Books
Nonfiction:
- Plant Breeding Reviews: Part 1: Long-term Selection: Maize, Volume 24, ed Janick 2004 (an anthology of papers on plant breeding efforts in, primarily, the Midwest, centering mostly on the famous long-term maize selection experiment; I was particularly interested in “Population Size and Long-term Selection”, Weber 2004, but was amazed to learn that the maize selection experiment, despite running for a century and still producing gains on some traits, was founded on a maize population size of just 4! This illustrates the untapped potential in existing genetic variance.)
Music
Touhou:
- “Kid’s Festival ～ Innocent Treasures” (Clonesoldier; Affect a mind {SC42}) [folk]
- “White Flag of Usa Shrine” (Clonesoldier; Affect a mind {SC42}) [folk]
- “Memory of Forgathering Dream” (U2; Affect a mind {SC42}) [folk]
Vocaloid:
- “Reverberations (Reverberations3 Remix)” (Clean Tears feat. Miku; Reverberations 3 {C92}) [trance]
- “Reminiscence” (Clean Tears feat. Miku; Reverberations 3 {C92}) [trance]
- “Into the Blue” (Bernis feat. Miku; On the shore of the Eden {M3-38}) [trance]
- “On the shore of the Eden” (Bernis feat. Miku; On the shore of the Eden {M3-38}) [trance]
- “みどりのつばさ” (You.T. feat. Miku; vita ex machina -inDiscipline- {VM2}) [electronic]
Misc:
- “You Are Enough” (El Ten Eleven; Banker’s Hill) [postrock]
- “We Don’t Have A Sail But We Have A Rudder” (El Ten Eleven; Banker’s Hill) [postrock]
- “Reverie” (El Ten Eleven; Banker’s Hill) [postrock]
- “This Morning With Her, Having Coffee” (El Ten Eleven; Banker’s Hill) [postrock]
Link Bibliography
Bibliography of page links in reading order (with annotations when available):
“August 2018 News”, (2018-08-01):
August 2018 gwern.net newsletter with links on genetic engineering, DRL, research quality, security, economics, and 4 book/movie reviews
“Gwern.net newsletter archives”, (2013-12-01):
Newsletter tag: archive of all issues back to 2013 for the gwern.net newsletter (monthly updates, which will include summaries of projects I’ve worked on that month (the same as the changelog), collations of links or discussions from my subreddit, and book/movie reviews.)
“Changelog”, (2013-09-15):
This page is a changelog for Gwern.net: a monthly reverse chronological list of recent major writings/
changes/ additions. Following my writing can be a little difficult because it is often so incremental. So every month, in addition to my regular /
r/ subreddit submissions, I write up reasonably-interesting changes and send it out to the mailing list in addition to a compilation of links & reviews (archives).Gwern “/r/gwern subreddit”, (2018-10-01):
A subreddit for posting links of interest and also for announcing updates to gwern.net (which can be used as a RSS feed). Submissions are categorized similar to the monthly newsletter and typically will be collated there.
“SMPY Bibliography”, (2018-07-28):
SMPY (Study of Mathematically Precocious Youth) is a long-running longitudinal survey of extremely mathematically-talented or intelligent youth, which has been following high-IQ cohorts since the 1970s. It has provided the largest and most concrete findings about the correlates and predictive power of screening extremely intelligent children, and revolutionized gifted & talented educational practices.
Because it has been running for over 40 years, SMPY-related publications are difficult to find; many early papers were published only in long-out-of-print books and are not available in any other way. Others are digitized and more accessible, but one must already know they exist. Between these barriers, SMPY information is less widely available & used than it should be given its importance.
To fix this, I have been gradually going through all SMPY citations and making fulltext copies available online with occasional commentary.
“Genomic prediction of cognitive traits in childhood and adolescence”, (2018-09-17):
Recent advances in genomics are producing powerful DNA predictors of complex traits, especially cognitive abilities. Here, we leveraged summary statistics from the most recent genome-wide association studies of intelligence and educational attainment to build prediction models of general cognitive ability and educational achievement. To this end, we compared the performances of multi-trait genomic and polygenic scoring methods. In a representative UK sample of 7,026 children at age 12 and 16, we show that we can now predict up to 11 percent of the variance in intelligence and 16 percent in educational achievement. We also show that predictive power increases from age 12 to age 16 and that genomic predictions do not differ for girls and boys. Multivariate genomic methods were effective in boosting predictive power and, even though prediction accuracy varied across polygenic scores approaches, results were similar using different multivariate and polygenic score methods. Polygenic scores for educational attainment and intelligence are the most powerful predictors in the behavioural sciences and exceed predictions that can be made from parental phenotypes such as educational attainment and occupational status.
“Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals”, (10.1038/
s41588-018-0147-3 ):Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11–13% of the variance in educational attainment and 7–10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
https:/
/ www.gwern.net/ images/ iq/ 2018-allegrini-figure2-iqpgs-mtaggsem.png “A Polygenic Score for Higher Educational Attainment is Associated With Larger Brains”, (2018):
People who score higher on intelligence tests tend to have larger brains. Twin studies suggest the same genetic factors influence both brain size and intelligence. This has led to the hypothesis that genetics influence intelligence partly by contributing to the development of larger brains. We tested this hypothesis using four large imaging genetics studies (combined N = 7965) with polygenic scores derived from a genome-wide association study (GWAS) of educational attainment, a correlate of intelligence. We conducted meta-analysis to test associations among participants’ genetics, total brain volume (i.e., brain size), and cognitive test performance. Consistent with previous findings, participants with higher polygenic scores achieved higher scores on cognitive tests, as did participants with larger brains. Participants with higher polygenic scores also had larger brains. We found some evidence that brain size partly mediated associations between participants’ education polygenic scores and their cognitive test performance. Effect sizes were larger in the population-based samples than in the convenience-based samples. Recruitment and retention of population-representative samples should be a priority for neuroscience research. Findings suggest promise for studies integrating GWAS discoveries with brain imaging to understand neurobiology linking genetics with cognitive performance.
“The genetic architecture of the human cerebral cortex”, (2020-03-20):
The human cerebral cortex is important for cognition, and it is of interest to see how genetic variants affect its structure. Grasby et al. combined genetic data with brain magnetic resonance imaging from more than 50,000 people to generate a genome-wide analysis of how human genetic variation influences human cortical surface area and thickness. From this analysis, they identified variants associated with cortical structure, some of which affect signaling and gene expression. They observed overlap between genetic loci affecting cortical structure, brain development, and neuropsychiatric disease, and the correlation between these phenotypes is of interest for further study.
Introduction: The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure.
Rationale: To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations.
Results: We identified 306 nominally genome-wide significant loci (p < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (p < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness).
Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rg = −0.32, SE = 0.05, p = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness.
To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity.
We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism.
Conclusion: This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function.
“The genetics of the mood disorder spectrum: genome-wide association analyses of over 185,000 cases and 439,000 controls”, (2018-08-13):
Mood disorders affect 10-20% of the population, ranging from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of genetic risk factors between unipolar and bipolar mood disorders. We use data from the largest genome-wide association studies of major depression (MD) and bipolar disorder (BD) to investigate the molecular basis of the shared genetic liability to mood disorders. We meta-analysed the Psychiatric Genomics Consortium (PGC) MD and BD cohorts, and an additional MD cohort from UK Biobank (185,285 cases, 439,741 controls, non-overlapping N = 609,424). 73 loci reached genome-wide significance in the meta-analysis, with additional loci significant in subtype and depression-only analyses. More genome-wide significant loci from PGC MD (39/44, 89% of the PGC MD loci) than PGC BD (4/19, 21%) reached genome-wide significance in the meta-analysis. Genetic correlations calculated between MD and BD subtypes revealed that type II BD correlates strongly with MD. Integrating the results with systems biology information, we implicate pathways and neuronal subtypes which highlight similarities but also potential differences between MD and BD. Our results reflected MD more than BD, perhaps due to the larger sample size for MD, but also perhaps because depression is their predominant common feature. Overall, these results provide evidence for a genetic mood disorders spectrum.
“Machine Learning to Predict Osteoporotic Fracture Risk from Genotypes”, (2018-09-11):
Background: Genomics-based prediction could be useful since genome-wide genotyping costs less than many clinical tests. We tested whether machine learning methods could provide a clinically-relevant genomic prediction of quantitative ultrasound speed of sound (SOS)—a risk factor for osteoporotic fracture.
Methods: We used 341,449 individuals from UK Biobank with SOS measures to develop genomically-predicted SOS (gSOS) using machine learning algorithms. We selected the optimal algorithm in 5,335 independent individuals and then validated it and its ability to predict incident fracture in an independent test dataset (N = 80,027). Finally, we explored whether genomic pre-screening could complement a UK-based osteoporosis screening strategy, based on the validated tool FRAX.
Results: gSOS explained 4.8-fold more variance in SOS than FRAX clinical risk factors (CRF) alone (r2 = 23% vs. 4.8%). A standard deviation decrease in gSOS, adjusting for the CRF-FRAX score was associated with a higher increased odds of incident major osteoporotic fracture (1,491 cases / 78,536 controls, OR = 1.91 [1.70-2.14], p = 10-28) than that for measured SOS (OR = 1.60 [1.50-1.69], p = 10-52) and femoral neck bone mineral density (147 cases / 4,594 controls, OR = 1.53 [1.27-1.83], p = 10-6). Individuals in the bottom decile of the gSOS distribution had a 3.25-fold increased risk of major osteoporotic fracture (P = 10-18) compared to the top decile. A gSOS-based FRAX score, identified individuals at high risk for incident major osteoporotic fractures better than the CRF-FRAX score (P = 10-14). Introducing a genomic pre-screening step into osteoporosis screening in 4,741 individuals reduced the number of required clinical visits from 2,455 to 1,273 and the number of BMD tests from 1,013 to 473, while only reducing the sensitivity to identify individuals eligible for therapy from 99% to 95%.
Interpretation
The use of genotypes in a machine learning algorithm resulted in a clinically-relevant prediction of SOS and fracture, with potential to impact healthcare resource utilization.
Research in Context
Evidence Before this Study
Genome-wide association studies have identified many loci associated with risk of clinically-relevant fracture risk factors, such as SOS. Yet, it is unclear if such information can be leveraged to identify those at risk for disease outcomes, such as osteoporotic fractures. Most previous attempts to predict disease risk from genotypes have used polygenic risk scores, which may not be optimal for genomic-prediction. Despite these obstacles, genomic-prediction could enable screening programs to be more efficient since most people screened in a population are not determined to have a level of risk that would prompt a change in clinical care. Genomic pre-screening could help identify individuals whose risk of disease is low enough that they are unlikely to benefit from screening.
Added Value of this Study
Using a large dataset of 426,811 individuals we trained and tested a machine learning algorithm to genomically-predict SOS. This metric, gSOS, had performance characteristics for predicting fracture risk that were similar to measured SOS and femoral neck BMD. Implementing a gSOS-based pre-screening step into the UK-based osteoporosis treatment guidelines reduced the number of individuals who would require screening clinical visits and skeletal testing by approximately 50%, while having little impact on the sensitivity to identify individuals at high risk for osteoporotic fracture.
Implications of all of the Available Evidence
Clinically-relevant genomic prediction of heritable traits is feasible using the machine learning algorithm presented here in large sample sizes. Genome-wide genotyping is now less expensive than many clinical tests, needs to be performed once over a lifetime and could risk stratify for multiple heritable traits and diseases years prior to disease onset, providing an opportunity for prevention. The implementation of such algorithms could improve screening efficiency, yet their cost-effectiveness will need to be ascertained in subsequent analyses.
“Common risk variants identified in autism spectrum disorder”, (2017-11-25):
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 ASD cases and 27,969 controls that identifies five genome-wide significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), seven additional loci shared with other traits are identified at equally strict significance levels. Dissecting the polygenic architecture we find both quantitative and qualitative polygenic heterogeneity across ASD subtypes, in contrast to what is typically seen in other complex disorders. 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, just as it has been in a broad range of important psychiatric and diverse medical phenotypes.
https:/
/ www.gwern.net/ docs/ genetics/ correlation/ 2017-robinson.pdf -
The parental feeding practices (PFPs) of excessive restriction of food intake (‘restriction’) and pressure to increase food consumption (‘pressure’) have been argued to causally influence child weight in opposite directions (high restriction causing overweight; high pressure causing underweight). However child weight could also ‘elicit’ PFPs. A novel approach is to investigate gene-environment correlation between child genetic influences on BMI and PFPs. Genome-wide polygenic scores (GPS) combining BMI-associated variants were created for 10,346 children (including 3,320 DZ twin pairs) from the Twins Early Development Study using results from an independent genome-wide association study meta-analysis. Parental ‘restriction’ and ‘pressure’ were assessed using the Child Feeding Questionnaire. Child BMI standard deviation scores (BMI-SDS) were calculated from children’s height and weight at age 10. Linear regression and fixed family effect models were used to test between-(n = 4,445 individuals) and within-family (n = 2,164 DZ pairs) associations between the GPS and PFPs. In addition, we performed multivariate twin analyses (n = 4,375 twin pairs) to estimate the heritabilities of PFPs and the genetic correlations between BMI-SDS and PFPs. The GPS was correlated with BMI-SDS (β=0.20, p=2.41×10-38). Consistent with the gene-environment correlation hypothesis, child BMI GPS was positively associated with ‘restriction’ (β=0.05, p=4.19×10-4), and negatively associated with ‘pressure’ (β=-0.08, p=2.70×10-7). These results remained consistent after controlling for parental BMI, and after controlling for overall family contributions (within-family analyses). Heritabilities for ‘restriction’ (43% [40-47%]) and ‘pressure’ (54% [50-59%]) were moderate-to-high. Twin-based genetic correlations were moderate and positive between BMI-SDS and ‘restriction’ (rA=0.28 [0.23-0.32]), and substantial and negative between BMI-SDS and ‘pressure’ (rA=-0.48 [-0.52 --0.44]. Results suggest that the degree to which parents limit or encourage children’s food intake is partly influenced by children’s genetic predispositions to higher or lower BMI. These findings point to an evocative gene-environment correlation in which heritable characteristics in the child elicit parental feeding behaviour.
Author Summary
It is widely believed that parents influence their child’s BMI via certain feeding practices. For example, rigid restriction has been argued to cause overweight, and pressuring to eat to cause underweight. However, recent longitudinal research has not supported this model. An alternative hypothesis is that child BMI, which has a strong genetic basis, evokes parental feeding practices (‘gene-environment correlation’). To test this, we applied two genetic methods in a large sample of 10-year-old children from the Twins Early Development Study: a polygenic score analysis (DNA-based score of common genetic variants robustly associated with BMI in genome-wide meta-analyses), and a twin analysis (comparing resemblance between identical and non-identical twin pairs). Polygenic scores correlated positively with parental restriction of food intake (‘restriction’; β=0.05, p=4.19×10-4), and negatively with parental pressure to increase food intake (‘pressure’; β=-0.08, p=2.70×10-7). Associations were unchanged after controlling for all genetic and environmental effects shared within families. Results from twin analyses were consistent. ‘Restriction’ (43%) and ‘pressure’ (54%) were substantially heritable, and a positive genetic correlation between child BMI and ‘restriction’ (rA=0.28), and negative genetic correlation between child BMI and ‘pressure’ (rA=-0.48) emerged. These findings challenge the prevailing view that parental behaviours are the sole cause of child BMI by supporting an alternate hypothesis that child BMI also causes parental feeding behaviour.
“Analysis of the genetic basis of height in large Jewish nuclear families”, (2018-04-17):
Despite intensive study, most genetic factors that contribute to variation in human height remain undiscovered. We conducted a family-based linkage study of height in a unique cohort of very large nuclear families from a founder (Jewish) population. This design allowed for increased power to detect linkage, compared to previous family-based studies. We identified loci that together explain an estimated 6% of the variance in height. We showed that these loci are not tagging known common variants associated with height. Rather, we suggest that the observed signals arise from variants with large effects that are rare globally but elevated in frequency in the Jewish population.
“Shawn Bradley”, (2020-12-28):
Shawn Paul Bradley is a German-American former professional basketball player who played center for the Philadelphia 76ers, New Jersey Nets, and Dallas Mavericks of the National Basketball Association (NBA). Nicknamed "the Stormin' Mormon", Bradley was one of the tallest players in NBA history at 7 ft 6 in (2.29 m). Bradley was born in Landstuhl, West Germany as his family was stationed at the U.S. Military base medical facility, and grew up in Castle Dale, Utah. He also holds German citizenship.
“Detecting past and ongoing natural selection among ethnically Tibetan women at high altitude in Nepal”, (2018-08-21):
Adaptive evolution in humans has rarely been characterized for its whole set of components, i.e. selective pressure, adaptive phenotype, beneficial alleles and realized fitness differential. We combined approaches for detecting polygenic adaptations and for mapping the genetic bases of physiological and fertility phenotypes in approximately 1000 indigenous ethnically Tibetan women from Nepal, adapted to high altitude. The results of genome-wide association analyses and tests for polygenic adaptations showed evidence of positive selection for alleles associated with more pregnancies and live births and evidence of negative selection for those associated with higher offspring mortality. Lower hemoglobin level did not show clear evidence for polygenic adaptation, despite its strong association with an EPAS1 haplotype carrying selective sweep signals.
Author summary: The adaptations to high altitude environments in Tibetan populations have long been highlighted as an important case study of adaptive evolution in our species. Recent genetic studies found two genes, EGLN1 and EPAS1, the genetic variants in which were swept to high frequency in Tibetans due to strong positive natural selection. However, it still remains unclear if and how these and other genetic variants are connected to adaptive phenotypes and ultimately to fitness advantage. In this study, we collected genotype and phenotype information of 1,000 ethnically Tibetan women from the high Himalayan valleys in Nepal. Using both genome-wide association analysis and test for polygenic adaptations, we show that natural selection systematically altered frequency of alleles associated with reproductive outcomes to the direction of increasing fitness. That is, alleles associated with more pregnancies and live births, as well as those associated with lower offspring mortality, were under positive selection. Omitting the EPAS1 haplotype under selective sweep, the other variants associated with lower hemoglobin did not collectively show a clear signal for polygenic adaptation. Our study highlights the polygenic nature of human adaptive traits.
“The palaeogenetics of cat dispersal in the ancient world”, (2017-06-19):
The cat has long been important to human societies as a pest-control agent, object of symbolic value and companion animal, but little is known about its domestication process and early anthropogenic dispersal. Here we show, using ancient DNA analysis of geographically and temporally widespread archaeological cat remains, that both the Near Eastern and Egyptian populations of Felis silvestris lybica contributed to the gene pool of the domestic cat at different historical times. While the cat’s worldwide conquest began during the Neolithic period in the Near East, its dispersal gained momentum during the Classical period, when the Egyptian cat successfully spread throughout the Old World. The expansion patterns and ranges suggest dispersal along human maritime and terrestrial routes of trade and connectivity. A coat-colour variant was found at high frequency only after the Middle Ages, suggesting that directed breeding of cats occurred later than with most other domesticated animals.
https:/
/ www.theatlantic.com/ science/ archive/ 2017/ 06/ cat-domination/ 530685/ http:/
/ nitro.biosci.arizona.edu:80/ zbook/ NewVolume_2/ pdf/ Chapter26.pdf https:/
/ www.gwern.net/ images/ genetics/ selection/ 2018-walsh-c26-weberfruitflyselectivebreeding.png http:/
/ blogs.sciencemag.org/ pipeline/ archives/ 2016/ 05/ 16/ evolution-in-action-literally https:/
/ www.nytimes.com/ 2018/ 09/ 04/ health/ synthetic-biology-pku.html “Phenylketonuria”, (2020-12-28):
Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated, PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight.
“The prehistory of biology preprints: A forgotten experiment from the 1960s”, (2017-11-16):
In 1961, the National Institutes of Health (NIH) began to circulate biological preprints in a forgotten experiment called the Information Exchange Groups (IEGs). This system eventually attracted over 3,600 participants and saw the production of over 2,500 different documents, but by 1967, it was effectively shut down following the refusal of journals to accept articles that had been circulated as preprints. This article charts the rise and fall of the IEGs and explores the parallels with the 1990s and the biomedical preprint movement of today.
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/ schmid-werren.ch/ hanspeter/ publications/ 2014elemath.pdf https:/
/ www.theatlantic.com/ health/ archive/ 2018/ 09/ victorian-vibrators-orgasms-doctors/ 569446/ https:/
/ www.nytimes.com/ 2018/ 09/ 21/ opinion/ the-dangers-of-dna-testing.html https:/
/ www.fsigenetics.com/ article/ S1872-4973(18)30248-5/ fulltext https:/
/ www.nytimes.com/ 2018/ 09/ 07/ us/ california-school-start-times.html “Hallucinogenic fish”, (2020-12-28):
Several species of fish are claimed to produce hallucinogenic effects when consumed. For example, Sarpa salpa, a species of sea bream, is commonly claimed to be hallucinogenic. These widely distributed coastal fish are normally found in the Mediterranean and around Spain, and along the west and south coasts of Africa. Occasionally they are found in British waters. They may induce hallucinogenic effects similar to LSD if eaten. However, based on the reports of exposure they are more likely to resemble hallucinogenic effects of deliriants than the effects of serotonergic psychedelics such as LSD. In 2006, two men who apparently ate the fish experienced hallucinations lasting for several days. The likelihood of hallucinations depends on the season. Sarpa salpa is known as "the fish that makes dreams" in Arabic.
“The Effect of Ad Blocking on User Engagement with the Web”, (2018-04-23):
Web users are increasingly turning to ad blockers to avoid ads, which are often perceived as annoying or an invasion of privacy. While there has been significant research into the factors driving ad blocker adoption and the detrimental effect to ad publishers on the Web, the resulting effects of ad blocker usage on Web users' browsing experience is not well understood. To approach this problem, we conduct a retrospective natural field experiment using Firefox browser usage data, with the goal of estimating the effect of adblocking on user engagement with the Web. We focus on new users who installed an ad blocker after a baseline observation period, to avoid comparing different populations. Their subsequent browser activity is compared against that of a control group, whose members do not use ad blockers, over a corresponding observation period, controlling for prior baseline usage. In order to estimate causal effects, we employ propensity score matching on a number of other features recorded during the baseline period. In the group that installed an ad blocker, we find significant increases in both active time spent in the browser (+28% over control) and the number of pages viewed (+15% over control), while seeing no change in the number of searches. Additionally, by reapplying the same methodology to other popular Firefox browser extensions, we show that these effects are specific to ad blockers. We conclude that ad blocking has a positive impact on user engagement with the Web, suggesting that any costs of using ad blockers to users' browsing experience are largely drowned out by the utility that they offer.
“Banner Ads Considered Harmful”, (2017-01-08):
One source of complexity & JavaScript use on Gwern.net is the use of Google AdSense advertising to insert banner ads. In considering design & usability improvements, removing the banner ads comes up every time as a possibility, as readers do not like ads, but such removal comes at a revenue loss and it’s unclear whether the benefit outweighs the cost, suggesting I run an A/
B experiment. However, ads might be expected to have broader effects on traffic than individual page reading times/ bounce rates, affecting total site traffic instead through long-term effects on or spillover mechanisms between readers (eg social media behavior), rendering the usual A/ B testing method of per-page-load/ session randomization incorrect; instead it would be better to analyze total traffic as a time-series experiment. Design: A decision analysis of revenue vs readers yields an maximum acceptable total traffic loss of ~3%. Power analysis of historical Gwern.net traffic data demonstrates that the high autocorrelation yields low statistical power with standard tests & regressions but acceptable power with ARIMA models. I design a long-term Bayesian
ARIMA(4,0,1)time-series model in which an A/B-test running January–October 2017 in randomized paired 2-day blocks of ads/ no-ads uses client-local JS to determine whether to load & display ads, with total traffic data collected in Google Analytics & ad exposure data in Google AdSense. The A/ B test ran from 2017-01-01 to 2017-10-15, affecting 288 days with collectively 380,140 pageviews in 251,164 sessions. Correcting for a flaw in the randomization, the final results yield a surprisingly large estimate of an expected traffic loss of −9.7% (driven by the subset of users without adblock), with an implied −14% traffic loss if all traffic were exposed to ads (95% credible interval: −13–16%), exceeding my decision threshold for disabling ads & strongly ruling out the possibility of acceptably small losses which might justify further experimentation.
Thus, banner ads on Gwern.net appear to be harmful and AdSense has been removed. If these results generalize to other blogs and personal websites, an important implication is that many websites may be harmed by their use of banner ad advertising without realizing it.
“Measuring Consumer Sensitivity to Audio Advertising: A Field Experiment on Pandora Internet Radio”, (2018-04-21):
A randomized experiment with almost 35 million Pandora listeners enables us to measure the sensitivity of consumers to advertising, an important topic of study in the era of ad-supported digital content provision. The experiment randomized listeners into 9 treatment groups, each of which received a different level of audio advertising interrupting their music listening, with the highest treatment group receiving more than twice as many ads as the lowest treatment group. By keeping consistent treatment assignment for 21 months, we are able to measure long-run demand effects, with three times as much ad-load sensitivity as we would have obtained if we had run a month-long experiment. We estimate a demand curve that is strikingly linear, with the number of hours listened decreasing linearly in the number of ads per hour (also known as the price of ad-supported listening). We also show the negative impact on the number of days listened and on the probability of listening at all in the final month. Using an experimental design that separately varies the number of commercial interruptions per hour and the number of ads per commercial interruption, we find that neither makes much difference to listeners beyond their impact on the total number of ads per hour. Lastly, we find that increased ad load causes a significant increase in the number of paid ad-free subscriptions to Pandora, particularly among older listeners.
“SonarSnoop: Active Acoustic Side-Channel Attacks”, (2018-08-30):
We report the first active acoustic side-channel attack. Speakers are used to emit human inaudible acoustic signals and the echo is recorded via microphones, turning the acoustic system of a smart phone into a sonar system. The echo signal can be used to profile user interaction with the device. For example, a victim’s finger movements can be inferred to steal Android phone unlock patterns. In our empirical study, the number of candidate unlock patterns that an attacker must try to authenticate herself to a Samsung S4 Android phone can be reduced by up to 70 can be easily applied to other application scenarios and device types. Overall, our work highlights a new family of security threats.
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/ www.brenthecht.com/ publications/ chi2018_wikipediavaluetoonlinecommunities.pdf “William Leonard Pickard”, (2020-12-28):
William Leonard Pickard is one of two people convicted in the largest lysergic acid diethylamide (LSD) manufacturing case in history. In 2000, while moving their LSD laboratory across Kansas, Pickard and Clyde Apperson were pulled over while driving a Ryder rental truck and a follow car. The laboratory had been stored near a renovated Atlas-E missile silo near Wamego, Kansas. Gordon Todd Skinner, one of the men intimately involved in the case but not charged due to his cooperation, owned the property where the laboratory equipment was stored.
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docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-01.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-02.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-02-2.pdf https:/
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/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-05-2.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-06.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-06-2.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-07.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-07-2.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-08.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-08-2.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-09.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-gordontoddskinner-09-2.pdf https:/
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docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-carlnichols-1.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-carlnichols-2.pdf /
docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-rogerely-1.pdf https:/
/ www.gwern.net/ docs/ sr/ pickard/ 2003-pickard-lsd-trial-transcript-rogerely-2.pdf http:/
/ www.faculty.ucr.edu/ ~eschwitz/ SchwitzPapers/ SF-MasterList-141103-byauthor.htm https:/
/ onlinelibrary.wiley.com/ doi/ book/ 10.1002/ 9780470650240 https:/
/ www.dropbox.com/ s/ d1v2mdu4m8npf27/ clonesoldier-affectamind-whiteflagofusashrine.ogg?dl=0 https:/
/ www.dropbox.com/ s/ 6qapl20z2md57bf/ u2-affectamind-memoryofforgatheringdream.ogg?dl=0 “El Ten Eleven”, (2020-12-28):
El Ten Eleven is an American, Los Angeles-based, post-rock duo, known for combining guitar/bass doubleneck or fretless bass, with heavy looping, or vamping, and the utility of an effects pedal, over acoustic or electric drumming. They have released seven full-length albums, 2 EPs and a remix album, earning generally positive reviews.
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/ www.topshelfrecords.com/ products/ 619339-el-ten-eleven-bankers-hill “Gwern.net newsletter (Substack subscription page)”, (2013-12-01):
Subscription page for the monthly gwern.net newsletter. There are monthly updates, which will include summaries of projects I’ve worked on that month (the same as the changelog), collations of links or discussions from my subreddit, and book/movie reviews. You can also browse the archives since December 2013.