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Record W2800482692 · doi:10.1093/hmg/ddy121

Genome-wide association study identifies nine novel loci for 2D:4D finger ratio, a putative retrospective biomarker of testosterone exposure in utero

2018· review· en· W2800482692 on OpenAlexfundno aff
Nicole M. Warrington, Enisa Shevroja, Gibran Hemani, Pirro G. Hysi, Yunxuan Jiang, Adam Auton, Cindy G. Boer, Massimo Mangino, Carol A. Wang, John P. Kemp, George McMahon, Carolina Medina‐Gómez, Martha Hickey, Katerina Trajanoska, Dieter Wolke, M. Arfan Ikram, Grant W. Montgomery, Janine F. Felix, Margaret J. Wright, David A. Mackey, Vincent W. V. Jaddoe, Nicholas G. Martin, Joyce Y. Tung, George Davey Smith, Craig E. Pennell, Tim D. Spector, Joyce B. J. van Meurs, Fernando Rivadeneira, Sarah E. Medland, David M. Evans

Bibliographic record

VenueHuman Molecular Genetics · 2018
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSexual Differentiation and Disorders
Canadian institutionsnot available
FundersH2020 European Research CouncilMedical Research CouncilNational Institutes of HealthGovernment of Western AustraliaErasmus Universiteit RotterdamEdith Cowan UniversityZonMwRaine Medical Research FoundationErasmus Medisch CentrumUniversity of BristolCurtin University of TechnologyEuropean CommissionAustralian Research CouncilKing's College LondonNational Health and Medical Research CouncilWomen and Infants Research FoundationNational Institute for Health and Care ResearchAustralian GovernmentQIMR Berghofer Medical Research InstituteNederlandse Organisatie voor Wetenschappelijk OnderzoekWellcome TrustCanadian Institutes of Health ResearchWellcome
KeywordsBiologyDigit ratioTestosterone (patch)Genome-wide association studyBiomarkerAndrogen receptorSex hormone-binding globulinGeneticsAndrogenPopulationSexual dimorphismMicrosatelliteGenotypeSingle-nucleotide polymorphismGeneEndocrinologyHormoneCancerProstate cancerAlleleMedicine

Abstract

fetched live from OpenAlex

The ratio of the length of the index finger to that of the ring finger (2D:4D) is sexually dimorphic and is commonly used as a non-invasive biomarker of prenatal androgen exposure. Most association studies of 2D:4D ratio with a diverse range of sex-specific traits have typically involved small sample sizes and have been difficult to replicate, raising questions around the utility and precise meaning of the measure. In the largest genome-wide association meta-analysis of 2D:4D ratio to date (N = 15 661, with replication N = 75 821), we identified 11 loci (9 novel) explaining 3.8% of the variance in mean 2D:4D ratio. We also found weak evidence for association (β = 0.06; P = 0.02) between 2D:4D ratio and sensitivity to testosterone [length of the CAG microsatellite repeat in the androgen receptor (AR) gene] in females only. Furthermore, genetic variants associated with (adult) testosterone levels and/or sex hormone-binding globulin were not associated with 2D:4D ratio in our sample. Although we were unable to find strong evidence from our genetic study to support the hypothesis that 2D:4D ratio is a direct biomarker of prenatal exposure to androgens in healthy individuals, our findings do not explicitly exclude this possibility, and pathways involving testosterone may become apparent as the size of the discovery sample increases further. Our findings provide new insight into the underlying biology shaping 2D:4D variation in the general population.

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)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.006
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.045
GPT teacher head0.339
Teacher spread0.294 · 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 designObservational
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

Citations48
Published2018
Admission routes1
Has abstractyes

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