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Record W2096669722 · doi:10.1371/journal.pgen.1002746

Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases

2012· review· en· W2096669722 on OpenAlexafffund
Rui Li, Felix F. Brockschmidt, Amy K. Kiefer, Hreinn Stefánsson, Dale R. Nyholt, Kijoung Song, Sita H. Vermeulen, Stavroula Kanoni, Daniel Glass, Sarah E. Medland, Maria Dimitriou, Dawn Waterworth, Joyce Y. Tung, Frank Geller, Stefanie Heilmann‐Heimbach, Axel M. Hillmer, Véronique Bataille, Sibylle Eigelshoven, S. Hanneken, Susanne Moebus, Christine Herold, Martin den Heijer, Grant W. Montgomery, Panos Deloukas, Nicholas Eriksson, Andrew C. Heath, Tim Becker, Patrick Sulem, Massimo Mangino, Péter Vollenweider, Tim D. Spector, George Dedoussis, Nicholas G. Martin, Lambertus A. Kiemeney, Vincent Mooser, Kāri Stefánsson, David A. Hinds, Markus M. Nöthen, J. Brent Richards

Bibliographic record

VenuePLoS Genetics · 2012
Typereview
Languageen
FieldMedicine
TopicHair Growth and Disorders
Canadian institutionsMcGill UniversityJewish General Hospital
FundersNational Institute of Mental HealthNational Institute on Alcohol Abuse and AlcoholismMedical Research CouncilCollege of Pharmacy, University of MichiganNational Institute for Health and Care ResearchJewish General HospitalNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungAustralian Research CouncilKing's College LondonHeinz Nixdorf StiftungGlaxoSmithKlineNational Health and Medical Research CouncilChronic Disease Research FoundationUniversity of MichiganChinese Society of Clinical OncologyNederlandse Organisatie voor Wetenschappelijk OnderzoekWellcome TrustCanadian Institutes of Health ResearchNational Science Foundation
KeywordsBiologyGeneticsOdds ratioLocus (genetics)HaplotypeAlleleGenome-wide association studyGenotypeGenetic associationSingle-nucleotide polymorphismInternal medicineMedicineGene

Abstract

fetched live from OpenAlex

Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62×10⁻⁹-1.01×10⁻¹²). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9×10⁻³). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4×10⁻⁸⁸]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.

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)0.003
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: none
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.048
GPT teacher head0.294
Teacher spread0.245 · 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

Citations130
Published2012
Admission routes2
Has abstractyes

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