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Record W3092045521 · doi:10.1038/s41597-020-00642-8

Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

2020· article· en· W3092045521 on OpenAlexaff
Solveig K. Sieberts, Thanneer M. Perumal, Minerva M. Carrasquillo, Mariet Allen, Joseph S. Reddy, Gabriel E. Hoffman, Kristen K. Dang, John Calley, Philip J. Ebert, James A. Eddy, Xue Wang, Anna K. Greenwood, Sara Mostafavi, Schahram Akbarian, Jaroslav Bendl, Michael S. Breen, Kristen Brennand, Leanne Brown, Andrew Browne, Joseph D. Buxbaum, Alexander W. Charney, Andrew Chess, Lizette Couto, Greg Crawford, Olivia Devillers, Bernie Devlin, Amanda Dobbyn, Enrico Domenici, Michele Filosi, Elie Flatow, Nancy Francoeur, John F. Fullard, Sergio Espeso‐Gil, Kiran Girdhar, Attila Gulyás-Kovács, Raquel E. Gur, Chang-Gyu Hahn, Vahram Haroutunian, Mads E. Hauberg, Laura M. Huckins, Rivky Jacobov, Yan Jiang, Jessica Johnson, Bibi Kassim, Yungil Kim, Lambertus Klei, Robin S. S. Kramer, Mario Lauria, Thomas Lehner, David A. Lewis, Barbara K. Lipska, Kelsey S. Montgomery, Royce Park, Chaggai Rosenbluh, Panagiotis Roussos, Douglas M. Ruderfer, Geetha Senthil, Hardik Shah, Laura Sloofman, Lingyun Song, Eli Stahl, Patrick Sullivan, Roberto Visintainer, Jiebiao Wang, Ying‐Chih Wang, Jennifer Wiseman, Eva Xia, Wen Zhang, Elizabeth Zharovsky, Laura Addis, Sadiya N. Addo, David Airey, Matthias Arnold, David A. Bennett, Yingtao Bi, Knut Biber, Colette Blach, Elizabeth Bradhsaw, Paul E. Brennan, Rosa Canet-Aviles, Sherry Cao, Anna Cavalla, Yooree Chae, William W. Chen, Jie Cheng, David Collier, Jeffrey L. Dage, Eric B. Dammer, J. Wade Davis, John B. Davis, Derek Drake, Duc M. Duong, Brian J. Eastwood, Michelle E. Ehrlich, Benjamin M. Ellingson, Brett W. Engelmann, Sahar Esmaeeli-Nieh, Daniel Felsky, Cory C. Funk, Chris Gaiteri, Sam Gandy, Fan Gao, O. Gileadi, Todd E. Golde, Shaun Grosskurth, Rishi R. Gupta, Alex Gutteridge, Basavaraj Hooli, Neil Humphryes-Kirilov, Koichi Iijima, Corey James, Paul Jung, Rima Kaddurah‐Daouk, Gabi Kastenmüller, Hans‐Ulrich Klein, Markus P. Kummer, Pascale N. Lacor, James J. Lah, Emma Laing, Allan I. Levey, Yupeng Li, Samantha Lipsky, Yushi Liu, Zhandong Liu, Gregory Louie, Tao Lu, Yiyi Ma, Yasuji Y. Matsuoka, Vilas Menon, Bradley B. Miller, Thomas P. Misko, J Mollon, Sumit Mukherjee, Scott Noggle, Ping‐Chieh Pao, Tracy Young Pearce, Neil Pearson, Michelle A. Penny, Vladislav Petyuk, Nathan D. Price, Danjuma Quarless, Brinda Ravikumar, Janina S. Ried, Cara Ruble, Heiko Runz, Andrew J. Saykin, Eric E. Schadt, James Scherschel, Nicholas T. Seyfried, Joshua Shulman, Phil Snyder, Holly Soares, Gyan Srivastava, Henning Stöckmann, Mariko Taga, Shinya Tasaki, Jessie Tenenbaum, Li‐Huei Tsai, Aparna Vasanthakumar, Astrid Wachter, Yaming Wang, Hong Wang, Minghui Wang, Christopher D. Whelan, Charles C. White, Kara Woo, Paul Wren, Jessica Wu, Hualin Simon Xi, Bruce A. Yankner, Steven G. Younkin, Lei Yu, Maria I. Zavodszky, Wenling Zhang, Guoqiang Zhang, Bin Zhang, Jun Zhu, Larsson Omberg, Mette A. Peters, Benjamin A. Logsdon, Philip L. De Jager, Nilüfer Ertekin‐Taner, Lara M. Mangravite

Bibliographic record

VenueScientific Data · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsPacific Centre for Reproductive MedicineUniversity of British ColumbiaCanadian Institute for Advanced Research
FundersNational Institute of Neurological Disorders and StrokeNational Institute on Drug AbuseNational Institute on AgingNational Institutes of HealthUniversità degli Studi di TrentoNational Institute of Mental HealthArizona Biomedical Research CommissionTranslational Genomics Research InstituteRush UniversityMichael J. Fox Foundation for Parkinson's ResearchArizona Department of Health ServicesCurePSPUniversity of PennsylvaniaMayo Foundation for Medical Education and ResearchF. Hoffmann-La RocheIllinois Department of Public HealthUniversity of PittsburghMayo Clinic
KeywordsMeta-analysisNeuroscienceCerebellumBiologyMedicineInternal medicine

Abstract

fetched live from OpenAlex

The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975).

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)0.012
metaresearch head score (Gemma)0.023
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.061

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0120.023
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.011
Bibliometrics0.0030.004
Science and technology studies0.0010.001
Scholarly communication0.0030.001
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.000

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 head0.097
GPT teacher head0.298
Teacher spread0.200 · 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 designMeta-analysis
Domainnot available
GenreEmpirical

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

Citations330
Published2020
Admission routes1
Has abstractyes

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