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Record W2972559905 · doi:10.3899/jrheum.190184

Analysis of 47 Non-MHC Ankylosing Spondylitis Susceptibility Loci Regarding Associated Variants across Whites and Han Chinese

2019· review· en· W2972559905 on OpenAlexvenueno aff
Xuqi Zheng, Qiuxia Li, Xiaomin Li, Yanli Zhang, Xinyu Wu, Qiujing Wei, Shuangyan Cao, Mingcan Yang, Zhiming Lin, Zetao Liao, Jun Qi, Qing Lv, Ling Wang, Yi Li, Astrid Irwanto, Ching‐Yu Cheng, Xiaoran Chai, Chiea Chuen Khor, Chew‐Kiat Heng, Woon‐Puay Koh, Jian‐Min Yuan, Jin‐Xin Bei, Furen Zhang, Xuejun Zhang, Yixin Zeng, Yan Shen, Jianjun Liu, Jieruo Gu

Bibliographic record

VenueThe Journal of Rheumatology · 2019
Typereview
Languageen
FieldMedicine
TopicSpondyloarthritis Studies and Treatments
Canadian institutionsnot available
FundersNational Cancer InstituteNational Institutes of HealthSun Yat-sen University Cancer CenterScience and Technology Planning Project of Guangdong ProvinceState Key Laboratory of Oncology in South ChinaPeking Union Medical CollegeGraduate School of Public Health, University of PittsburghAgency for Science, Technology and ResearchHuashan HospitalChinese Academy of Medical SciencesFudan UniversityGenome Institute of SingaporeMedical Research CouncilUniversity of PittsburghNational Research Foundation SingaporeShandong First Medical UniversitySun Yat-sen UniversityNational Medical Research CouncilNational Research FoundationShandong Academy of Medical SciencesNational Supercomputer Centre in GuangzhouAnhui Medical UniversityDuke-NUS Medical SchoolNational University Health System
KeywordsSNPSingle-nucleotide polymorphismGeneticsImputation (statistics)BiologyEpistasisGenetic associationHan chineseHuman leukocyte antigenGeneGenotype

Abstract

fetched live from OpenAlex

Objective. To present a systematic evaluation of 47 non-MHC ankylosing spondylitis (AS) susceptibility loci that have been initially discovered through white genome-wide association studies in Han Chinese. Methods. Originally, 10,743 samples representing north and south Chinese in 4 datasets were obtained. After data quality control and imputation, metaanalysis results of 94,621 variants within 47 loci were extracted. Four ERAP1 single-nucleotide polymorphisms (SNP) and HLA-B27 tag SNP rs13202464 were used for interaction analysis. Population-attributable risk percentages of AS-associated variants were compared. Functional annotations of AS-associated variants were conducted using HaploReg, RegulomeDB, and rVarBase databases. Results. We revealed 16 AS-associated variants with nominal evidence in Han Chinese, including rs10865331 (p = 6.30 × 10−10), rs10050860 (p = 4.09 × 10−5) and rs8070463 (p = 1.03 × 10−4). Potential susceptible SNP within these 47 loci were also identified, such as rs13024541 (2p15), rs17401719 (5q15), and rs62074054 (17q21). Epistatic interactions between 3 ERAP1 SNP (rs17401719, rs30187, and rs10050860) and HLA-B27 were confirmed. Among the 16 AS-associated variants, rs30187 showed weaker risk effect, while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than in whites. Further genomic annotation pinpointed 35 candidate functional SNP, especially in the 2p15, ERAP1, and NPEPPS-TBKBP1 regions. Conclusion. Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1, and NPEPPS-TBKBP1 regions may play a critical role in AS pathogenesis across diverse populations.

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)0.004
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.008
Threshold uncertainty score0.023

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.004
Bibliometrics0.0030.005
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0000.000
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 head0.028
GPT teacher head0.348
Teacher spread0.319 · 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 designSystematic review
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

Citations12
Published2019
Admission routes1
Has abstractyes

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