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Record W2789305195 · doi:10.1038/s41467-018-04558-1

Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood

2018· review· en· W2789305195 on OpenAlexaff
Ting Qi, Yang Wu, Jian Zeng, Futao Zhang, Angli Xue, Longda Jiang, Zhihong Zhu, Kathryn E. Kemper, Loïc Yengo, Zhili Zheng, Mawussé Agbessi, Habibul Ahsan, Isabel Alves, Anand Kumar Andiappan, Philip Awadalla, Alexis Battle, Frank Beutner, Marc Jan Bonder, Dorret I. Boomsma, Mark Christiansen, Annique Claringbould, Patrick Deelen, Tõnu Esko, Marie-Julie Favé, Lude Franke, Timothy M. Frayling, Sina A. Gharib, Gregory Gibson, Gibran Hemani, Rick Jansen, Mika Kähönen, Anette Kalnapenkis, Silva Kasela, Johannes Kettunen, Yungil Kim, Holger Kirsten, Péter Kovács, Knut Krohn, Jaanika Kronberg-Guzman, Viktorija Kukushkina, Zoltán Kutalik, Bernett Lee, Terho Lehtimäki, Markus Loeffler, Urko M. Marigorta, Andres Metspalu, Lili Milani, Martina Müller‐Nurasyid, Matthias Nauck, Michel G. Nivard, Brenda W.J.H. Penninx, Markus Perola, Natalia Pervjakova, Brandon L. Pierce, Joseph E. Powell, Holger Prokisch, Bruce M. Psaty, Olli T. Raitakari, Susan M. Ring, Samuli Ripatti, Olaf Rötzschke, Sina Rüeger, Ashis Saha, Markus Scholz, Katharina Schramm, Ilkka Seppälä, Michael Stümvoll, Patrick Sullivan, Alexander Teumer, Joachim Thiery, Tong Lin, Anke Tönjes, Jenny van Dongen, Joyce B. J. van Meurs, Joost Verlouw, Uwe Völker, Urmo Võsa, Hanieh Yaghootkar, Biao Zeng, Riccardo E. Marioni, Grant W. Montgomery, Ian J. Deary, Naomi R. Wray, Peter M. Visscher, Allan F. McRae, Jian Yang

Bibliographic record

VenueNature Communications · 2018
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsOntario Institute for Cancer Research
FundersNational Institute on AgingWellcome TrustAustralian Research CouncilNational Institute of General Medical SciencesMedical Research CouncilNational Institutes of HealthNational Health and Medical Research Council
KeywordsTranscriptomeComputational biologyBiologyGeneData scienceComputer scienceGeneticsGene expression

Abstract

fetched live from OpenAlex

Abstract Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis -expression or -DNA methylation (DNAm) quantitative trait loci ( cis -eQTLs or cis -mQTLs) between brain and blood ( r b ). Using publicly available data, we find that genetic effects at the top cis -eQTLs or mQTLs are highly correlated between independent brain and blood samples ( $$\hat r_b = 0.70$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mover> <mml:mrow> <mml:mi>r</mml:mi> </mml:mrow> <mml:mo>^</mml:mo> </mml:mover> </mml:mrow> <mml:mrow> <mml:mi>b</mml:mi> </mml:mrow> </mml:msub> <mml:mo>=</mml:mo> <mml:mn>0.70</mml:mn> </mml:math> for cis -eQTLs and $$\hat r_ b = 0.78$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mover> <mml:mrow> <mml:mi>r</mml:mi> </mml:mrow> <mml:mo>^</mml:mo> </mml:mover> </mml:mrow> <mml:mrow> <mml:mi>b</mml:mi> </mml:mrow> </mml:msub> <mml:mo>=</mml:mo> <mml:mn>0.78</mml:mn> </mml:math> for cis -mQTLs). Using meta-analyzed brain cis -eQTL/mQTL data ( n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes ( n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis -eQTL/mQTL data with large sample sizes.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.811
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.139
GPT teacher head0.417
Teacher spread0.279 · 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 teacher head, not a consensus.

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

Citations466
Published2018
Admission routes1
Has abstractyes

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