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Record W2133218791 · doi:10.1093/hmg/ddt087

Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network

2013· article· en· W2133218791 on OpenAlexaff
Zhao Chen, Hua Tang, Rehan Qayyum, Ursula M. Schick, Michael A. Nalls, Robert E. Handsaker, Jin Li, Yingchang Lu, Lisa R. Yanek, Brendan J. Keating, Yan Meng, Frank J.A. van Rooij, Yukinori Okada, Michiaki Kubo, Laura J. Rasmussen‐Torvik, Margaux F. Keller, Leslie A. Lange, Michele K. Evans, Erwin P. Böttinger, Michael D. Linderman, Douglas M. Ruderfer, Håkon Håkonarson, George Papanicolaou, Alan B. Zonderman, Omri Gottesman, Cynthia A. Thomson, Elad Ziv, Andrew B. Singleton, Ruth J. F. Loos, Patrick Sleiman, Santhi K. Ganesh, Steven A. McCarroll, Diane M. Becker, James G. Wilson, Guillaume Lettre, Alex P. Reiner

Bibliographic record

VenueHuman Molecular Genetics · 2013
Typearticle
Languageen
FieldMedicine
TopicHemoglobinopathies and Related Disorders
Canadian institutionsMontreal Heart Institute
FundersNational Institute on Minority Health and Health DisparitiesNational Center for Advancing Translational SciencesNational Center for Research ResourcesNational Institute of Nursing ResearchWake Forest UniversityNational Cancer InstituteChildren's Hospital of PhiladelphiaRIKENU.S. Public Health ServiceAndrea and Charles Bronfman PhilanthropiesHjartaverndNational Human Genome Research InstituteMinistry of Education, Culture, Sports, Science and TechnologyJackson State UniversityNederlandse Organisatie voor Wetenschappelijk OnderzoekNational Heart, Lung, and Blood InstituteMinistero della SaluteErasmus Medisch CentrumJohns Hopkins UniversityZonMwSchool of Medicine, Boston UniversityEuropean CommissionBroad InstituteNational Center on Minority Health and Health DisparitiesNational Institute on AgingNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsBiologyGeneticsLocus (genetics)Single-nucleotide polymorphismGenome-wide association studyMean corpuscular volumeGenetic associationHematocritRed blood cell distribution widthMean corpuscular hemoglobin concentrationQuantitative trait locusSNPGenotypeGeneInternal medicineEndocrinologyMedicine

Abstract

fetched live from OpenAlex

Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.

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)0.002
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.002
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.000
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 head0.008
GPT teacher head0.220
Teacher spread0.212 · 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
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

Citations76
Published2013
Admission routes1
Has abstractyes

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