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The origins and evolution of genetic disease risk in modern humans

2010· review· en· W1554239135 on OpenAlexaff
Bernard J. Crespi

Bibliographic record

VenueAnnals of the New York Academy of Sciences · 2010
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsSimon Fraser University
Fundersnot available
KeywordsPleiotropyBiologyDiseasePhenotypeAdaptation (eye)GeneticsSelection (genetic algorithm)Evolutionary biologyPolygeneGeneNeuroscienceQuantitative trait locusMedicine

Abstract

fetched live from OpenAlex

Patterns and risks of human disease have evolved. In this article, I review evidence regarding the importance of recent adaptive evolution, positive selection, and genomic conflicts in shaping the genetic and phenotypic architectures of polygenic human diseases. Strong recent selection in human populations can create and maintain genetically based disease risk primarily through three processes: increased scope for dysregulation from recent human adaptations, divergent optima generated by intraspecific genomic conflicts, and transient or stable deleterious by-products of positive selection caused by antagonistic pleiotropy, ultimately due to trade-offs at the levels of molecular genetics, development, and physiology. Human disease due to these processes appears to be concentrated in three sets of phenotypes: cognition and emotion, reproductive traits, and life-history traits related to long life-span. Diverse, convergent lines of evidence suggest that a small set of tissues whose pleiotropic patterns of gene function and expression are under especially strong selection-brain, placenta, testis, prostate, breast, and ovary-has mediated a considerable proportion of disease risk in modern humans.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0020.002
Science and technology studies0.0000.001
Scholarly communication0.0010.002
Open science0.0010.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.071
GPT teacher head0.369
Teacher spread0.297 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations55
Published2010
Admission routes1
Has abstractyes

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