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Record W2902801700 · doi:10.2337/db18-0567

Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control

2018· review· en· W2902801700 on OpenAlex
Samuela Pollack, Robert P. Igo, Richard A. Jensen, Mark Christiansen, Xiaohui Li, Ching‐Yu Cheng, Maggie C. Y. Ng, Albert V. Smith, Elizabeth J. Rossin, Ayellet V. Segrè, Samaneh Davoudi, Gavin Siew Wei Tan, Yii‐Der Ida Chen, Jane Z. Kuo, Latchezar Dimitrov, Lynn K. Stanwyck, Weihua Meng, Sayed Mohsen Hosseini, Minako Imamura, Darryl Nousome, Jihye Kim, Yang Hai, Yucheng Jia, Jeeyun Ahn, Aaron Leong, Kaanan P. Shah, Kyu Hyung Park, Xiuqing Guo, Eli Ipp, Kent D. Taylor, Sharon G. Adler, John R. Sedor, Barry I. Freedman, I‐Te Lee, Wayne H.-H. Sheu, Michiaki Kubo, Atsushi Takahashi, Samy Hadjadj, Michel Marre, David‐Alexandre Trégouët, Roberta McKean‐Cowdin, Rohit Varma, Mark I. McCarthy, Emma Ahlqvist, Valeriya Lyssenko, Elisabet Agardh, Andrew P. Morris, Alex S. F. Doney, Helen M. Colhoun, Iiro Toppila, Niina Sandholm, Per‐Henrik Groop, Shiro Maeda, Craig L. Hanis, Alan D. Penman, Ching J. Chen, Heather Hancock, Paul Mitchell, Jamie E. Craig, Emily Y. Chew, Andrew D. Paterson, Michael A. Grassi, Donald W. Bowden, Brian L. Yaspan, David Siscovick, Mary Frances Cotch, Jie Jin Wang, Kathryn P. Burdon, Tien Yin Wong, Barbara E.K. Klein, Ronald Klein, Jerome I. Rotter, Sudha K. Iyengar, Alkes L. Price, Lucia Sobrin

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueDiabetes · 2018
Typereview
Languageen
FieldMedicine
TopicRetinal Diseases and Treatments
Canadian institutionsPublic Health OntarioUniversity of TorontoHospital for Sick Children
FundersAlcon Research InstituteNational Center for Advancing Translational SciencesNational Center for Research ResourcesNational Institute of Environmental Health SciencesNational Institute of Neurological Disorders and StrokeNational Human Genome Research InstituteOphthalmic Research Institute of AustraliaBiomedical Research CouncilNational Medical Research CouncilTaichung Veterans General HospitalWake Forest School of MedicineNational Institutes of HealthHjartaverndWellcomeInnovative Medicines InitiativeCase Western Reserve UniversityNovo Nordisk FondenNovo NordiskMedical Research CouncilWake Forest UniversityNational Research Foundation of KoreaFolkhälsanin TutkimussäätiöNational Institute for Health and Care ResearchNational Eye InstituteUniversity of DundeeSamfundet FolkhälsanAcademy of FinlandNational Science CouncilU.S. Department of Health and Human ServicesNational Institute of Diabetes and Digestive and Kidney DiseasesHelsingin ja Uudenmaan SairaanhoitopiiriTenovusDiabetes UKNational Institute on AgingWellcome TrustResearch to Prevent BlindnessWilhelm och Else Stockmanns StiftelseNational Heart, Lung, and Blood InstituteNational Cancer InstituteHealth Sciences Center, University of New MexicoHarvard CatalystJohns Hopkins UniversityMassachusetts Lions Eye Research FundHáskóli ÍslandsNational Institute on Minority Health and Health DisparitiesEuropean CommissionGenentechAstraZenecaJackson State UniversityNational Health and Medical Research CouncilEli Lilly and CompanyAmerican Diabetes AssociationBroad InstituteSanofiUniversity of California, Irvine
KeywordsGlycemicGenome-wide association studyDiseaseDiabetes mellitusBiologyGenetic associationSingle-nucleotide polymorphismGeneGeneticsMedicineOncologyInternal medicineBioinformaticsEndocrinologyGenotype

Abstract

fetched live from OpenAlex

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value <1 × 10−5 were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like (NVL) was associated with DR in European discovery cohorts (P = 2.1 × 10−9), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein–protein interaction network built from genes in regions associated with proliferative DR was found to have significant connectivity (P = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in NVL, as well as variation within a protein–protein interaction network that includes genes implicated in inflammation, may influence risk for DR.

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.

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)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.589
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0030.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.040
GPT teacher head0.316
Teacher spread0.275 · 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