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New Blood Pressure–Associated Loci Identified in Meta-Analyses of 475 000 Individuals

2017· article· en· W2762813577 on OpenAlexfundno aff

Bibliographic record

VenueCirculation Cardiovascular Genetics · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersInstitute of GeneticsNational Institute of Environmental Health SciencesNational Center for Research ResourcesNational Institute of General Medical SciencesNHLBI Division of Intramural ResearchNational Institute on AgingNIHR Leicester Biomedical Research CentreNIHR Oxford Biomedical Research CentreBarts and The London School of Medicine and DentistrySchool of Medicine, Stanford UniversityUniversity of IoanninaSygehus LillebæltHjartaverndNovo Nordisk Foundation Center for Basic Metabolic ResearchUniwersytet Medyczny im. Karola Marcinkowskiego w PoznaniuVaasan KeskussairaalaNovo Nordisk FondenMedical Research CouncilUppsala UniversitetTartu ÜlikoolNational Center for Advancing Translational SciencesEconomic and Social Research CouncilUniversità degli Studi di VeronaNational Institute of Mental HealthSyddansk UniversitetDeutsches Zentrum für Herz-KreislaufforschungUniversitair Medisch Centrum GroningenUniversità Cattolica del Sacro CuoreUniversity of DundeeSamfundet FolkhälsanCentre for Cognitive Ageing and Cognitive EpidemiologyDasman Diabetes InstituteKuopion Yliopistollinen SairaalaRegion HovedstadenNovo NordiskFaculty of Health and Medical Sciences, University of Western AustraliaNational University of SingaporeBritish Heart FoundationHáskóli ÍslandsKing Abdulaziz UniversityUniversity of BristolOulun YliopistoUniversity of GlasgowRijksuniversiteit GroningenDonau-Universität KremsUniversity of LeicesterMcGovern Medical SchoolVanderbilt University Medical CenterImperial College LondonNational Human Genome Research InstituteSchool of Medicine, Vanderbilt UniversityRigshospitaletUniversity of Texas Health Science Center at HoustonNational Institute for Health and Care ResearchDet Sundhedsvidenskabelige Fakultet, Københavns UniversitetUniversity of North Carolina at Chapel HillScience for Life LaboratoryQueen Mary University of LondonHarvard T.H. Chan School of Public HealthWellcome TrustNational Cancer InstituteLundbeckfondenUniversity College LondonImperial College Healthcare NHS TrustErasmus Medisch CentrumUniversity of OxfordNational Institutes of HealthVanderbilt-Ingram Cancer CenterUniversity of WashingtonBrigham and Women's HospitalNational Heart, Lung, and Blood InstituteBiotechnology and Biological Sciences Research CouncilItä-Suomen YliopistoNational Institute of Diabetes and Digestive and Kidney DiseasesHelsingin ja Uudenmaan SairaanhoitopiiriMassachusetts General HospitalMRC-PHE Centre for Environment and HealthUmeå UniversitetTaysSteno Diabetes Center CopenhagenLunds UniversitetTerveyden ja hyvinvoinnin laitosKing's College LondonHarokopio UniversityVanderbilt University
KeywordsGeneAlleleGenetic variationCandidate genePhenotypeGene expressionHaplotypeFunction (biology)Expression quantitative trait loci

Abstract

fetched live from OpenAlex

Background— Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results— Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant ( P <5×10 − 8 ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP ), rs7437940 ( AFAP1 ), rs13303 (missense, STAB1 ), and rs1055144 ( 7p15.2 ). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L ) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH ) was genome-wide significant. Conclusions— We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.

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)0.010
metaresearch head score (Gemma)0.015
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: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.010
Threshold uncertainty score0.055

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0100.015
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0050.022
Bibliometrics0.0040.007
Science and technology studies0.0010.001
Scholarly communication0.0030.001
Open science0.0020.002
Research integrity0.0020.002
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 head0.091
GPT teacher head0.332
Teacher spread0.241 · 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".

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Citations46
Published2017
Admission routes1
Has abstractyes

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