The differential biology reader

by Mark James Adams A worker in quantitative genetics, primate psychology, behavioral ecology, and psychiatric genetics.

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The bottom line is that evolutionary theory sheds light on how empirically successful methods in statistical genetics operate. It further simplifies those models to achieve better interpretability and scalability by leaving only biologically relevant parts of the model.

— Hanbin Lee

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Copy of a hand-written and hand-drawn page from Martin Boocock’s ‘Topological Tables’ (~1982). These set out to describe the topologies and outcomes of recombination events on recombination sites in different configurations. These Tables provided the basis for understand the resolvase recombination mechanism and the concept of a ‘topological filter’

David Sherratt, The journey of a molecular detective. Heredity.

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When Times New Ro­man ap­pears in a book, doc­u­ment, or ad­ver­tise­ment, it con­notes ap­a­thy. It says, “I sub­mit­ted to the font of least re­sis­tance.” Times New Ro­man is not a font choice so much as the ab­sence of a font choice, like the black­ness of deep space is not a color.

Matthew Butterick, "Times New Roman alternatives: You can do better"

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I am not interested in twins because they are an imperfect method to estimate heritability; I am interested in the concept of heritability because it might imperfectly help explain why twins are so similar.

Kathryn Paige Harden, "Twins Are So Much More Interesting Than Heritability Estimates"

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Why have we encountered so much apparent misunderstanding of the methods and results in the human genetics community? The core of our method is heavily steeped in the tradition of prediction of random effects and the estimation of variance due to random (latent) effects. While estimation and partitioning of variance has a long history in human genetics, in particular in twin research, the prediction of random effects is alien to many human geneticists and, surprisingly, also to statisticians.

Visscher, Yang, Goddard. A Commentary on ‘Common SNPs Explain a Large Proportion of the Heritability for Human Height’ by Yang et al. (2010).

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Edwin H. Land, “Experiments in Color Vision”. Scientific American. Vol. 200, No. 5 (May 1959), pp. 84-99 (16 pages)

Via New Look, Same Great Look by Kim Beil:

“Land’s research undertaken in the mid-1950s first showed that the eye can perceive color in images that are, by other measurements, monochromatic. Land and his team made two monochromatic still lifes of colored scientific equipment: one through a filter that allowed the passage only of long wavelengths (red filter) and the other for short wavelengths (green filter). They then projected the pair of monochromatic transparencies onto a screen and placed a red filter over the projector’s beam. Classical theories would suggest that the resulting image should contain only shades of pink and red. However, viewers discerned varied colors in the scene, which included multicolored pigments in vials and scientific instruments on a table. The colored objects were perceived as if in full color. Color film and other measurement systems, such as spectrometers, recognized only the shades of red in the image, but the visual cortex responded to the differences in wavelength and reconstructed color in the scene by comparison. (Ironically, when this research was published in Scientific American in 1959, Land had to provide artificially colored photographs that reconstructed what the human observers saw, since photographs couldn’t capture the images as perceived.)”

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sum scoring corresponds to a statistical model and is not a model-free arithmetic calculation

McNeish & Wolf. Thinking twice about sum scores. 2020

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Just because it's turtles all the way down, doesn't mean it's turtles all the way up…

Kevin Mitchell

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if study participants’ genetic information is available, large-scale reporting of population-level variant-disease associations enables easy reconstruction of individuals’ disease states.

Rather than being a challenge to genetic privacy, being able to reconstruct an individual's disease state using polygenic profiling is precisely the hope of association study summary statistics. Accurate reconstruction makes the study a success.

Lumley and Rice, Potential for Revealing Individual-Level Information in Genome-wide Association Studies

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there are delicate inferential problems when _n_ < _p_ that animal breeders often ignore in a somewhat naïve quest to unravel genetic architecture via statistical modeling

"A contradiction is that the basic model of quantitative genetics assumes random genotypes and fixed substitution effects, but whole-genome prediction models use realized genotypes (thus fixed) and random marker effects. This contradiction must be kept in mind for properly interpreting concepts such as genomic heritability and genomic correlations between traits"

Gianola, D., & Rosa, G. J. M. (2015). One Hundred Years of Statistical Developments in Animal Breeding. Annual Review of Animal Biosciences, 3(1), 19–56.

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Figure 2. Longitudinal associations between five-factor model personality traits and depressive symptoms adjusted for baseline depressive symptoms. Values are regression coefficients (and 95% confidence intervals) per 1 SD increment in personality trait. Personality traits are also adjusted for each other in addition to sex, age, and race/ethnicity. BHPS, British Household Panel Survey; GSOEP, German Socio-Economic Panel Study; HILDA, Household, Income and Labour Dynamics in Australia; HRS, Health and Retirement Study; MIDUS, Midlife in the United States; WLSG, Wisconsin Longitudinal Study Graduate Sample; WLSS, Wisconsin Longitudinal Study Sibling Sample.

Hakulinen, C., Elovainio, M., Pulkki-Råback, L., Virtanen, M., Kivimäki, M., & Jokela, M. (2015). PERSONALITY AND DEPRESSIVE SYMPTOMS: INDIVIDUAL PARTICIPANT META‐ANALYSIS OF 10 COHORT STUDIES. Depression and Anxiety

This meta-analysis shows the feedback between personality (usually conceived of as a stable trait) and depressive symptoms. Neuroticism is prospectively associated with depression, indicating its dispositional component, and Neuroticism also slightly increases after the onset of depression, its reactive component.

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"In depressive states the mind may be seen in the image of such an antler, in all its fantastic splendor pinning its bearer to the ground." — Peter Wessel Zapffe

Joel Benjamin, illustrating What You Call Depression I Call the Truth.

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Perhaps this is what they mean on the depression questionnaire when they say, "Have you lost interest in activities you once enjoyed?" They say it like losing interest is a bad thing. But what if the truth is that those activities were always stupid, meaningless, and destructive? What if I am getting closer to a higher truth?

What You Call Depression I Call the Truth by So Sad Today.

This question is similar to the anhedonia in many depression scales and diagnostic instruments. It often serves as a screening question (along with low mood) that can trigger further probings of depressive symptoms.

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Heritability of psychiatric traits

And before you say: "psychiatric genetics is a waste of time", check this heritability slide by @jamesjcrowley pic.twitter.com/0ysSj1uh7l

— Christian Rück (@christianruck) May 15, 2015

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I dub the “A/B illusion” the widespread tendency to view a field experiment designed to study the effects of an existing or proposed practice as more morally suspicious than a practitioner’s alternative of immediately implementing an untested practice. The A/B illusion…can cause us to overregulate research and underprotect a practice’s end-users. For instance, given probative but inconclusive evidence that News Feed psychologically harms users through exposure to negative and/or positive posts, Facebook’s unique position to establish the effects of its innovation, and the relative ease with which it could do so, most criticisms of the Facebook experiment reflect the A/B illusion and should be inverted: It is not the practitioner who engages in A/B testing but the practitioner who simply implements A who is more likely to exploit her position of power over users or employees, to treat them as mere means to the corporation’s ends, and to deprive them of information necessary for them to make a considered judgment about what is in their best interests.

Michelle N. Meyer, Two Cheers for Corporate Experimentation: The A/B Illusion and the Virtues of Data-Driven Innovation, SSRN

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Number needed to treat (NNT) for many medications is small. It would be interesting to plot this against prevelance.

Personalized medicine: Time for one-person trials : Nature News & Comment