SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 30, 2024

Limited whole genome sequencing (WGS) studies in Asian populations result a lack of representative reference panels, thus hindering the discovery ancestry-specific variants. Here, we present South and East Database (SEAD) panel ( https://imputationserver.westlake.edu.cn/ ), which integrates WGS data for 11,067 individuals from various sources across 17 countries. The SEAD panel, comprising 22,134 haplotypes 88,294,957 variants, demonstrates improved imputation accuracy compared to 1000 Genomes Project, TOPMed, ChinaMAP with higher proportion well-imputed rare For populations, shows concordance comparable ChinaMAP, but outperforming TOPMed. Additionally, apply conduct genome-wide association study total hip (Hip) femoral neck (FN) bone mineral density (BMD) traits 5369 genotyped Chinese samples. single-variant test suggests that variants near SNTG1 are associated Hip BMD (rs60103302, MAF = 0.0092, P 1.67 × 10-7), variant-set analysis further supports (Pslide_window 9.08 10-9, Pgene_centric 5.27 10-8). This was not reported previously can only be detected by using panels. Preliminary vitro experiments one identified provide evidence it upregulates expression, could turn inhibit proliferation differentiation preosteoblasts.

Language: Английский

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Massively parallel variant-to-function mapping determines functional regulatory variants of non-small cell lung cancer

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 6, 2025

Genome-wide association studies have identified thousands of genetic variants associated with non-small cell lung cancer (NSCLC), however, it is still challenging to determine the causal and improve disease risk prediction. Here, we applied massively parallel reporter assays perform NSCLC variant-to-function mapping at scale. A total 1249 candidate were evaluated, 30 potential within 12 loci identified. Accordingly, proposed three architectures underlying susceptibility: multiple in a single haplotype block (e.g. 4q22.1), blocks 5p15.33), variant 20q11.23). We developed modified polygenic score using from Chinese populations, improving performance prediction 450,821 Europeans UK Biobank. Our findings not only augment understanding architecture susceptibility but also provide strategy advance stratification. Determining GWAS crucial for mechanisms. authors apply MPRA (NSCLC) scale propose distinct susceptibility.

Language: Английский

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Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: April 5, 2025

Non-obstructive azoospermia, a severe form of male infertility caused by spermatogenic failure (SPGF), has largely unknown genetic basis across ancestries. To our knowledge, this is the first trans-ethnic meta-analysis genome-wide association studies on SPGF, involving 2255 men with idiopathic SPGF and 3608 controls from European Asian populations. Using logistic regression inverse variance methods, we identify two significant associations Sertoli cell-only (SCO) syndrome, most extreme phenotype. The G allele rs34915133, in major histocompatibility complex class II region, significantly increases SCO risk (P = 5.25E-10, OR 1.57), supporting potential immune-related cause. Additionally, rs10842262 variant SOX5 gene region also marker 5.29E-09, 0.72), highlighting key role reproductive function. Our findings reveal shared factors ancestries provide insights into molecular mechanisms underlying SCO.

Language: Английский

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Genome-driven Chinese precision medicine: Biobank-scale genomic research as a new paradigm

The Innovation Life, Journal Year: 2025, Volume and Issue: unknown, P. 100131 - 100131

Published: Jan. 1, 2025

<p>Large-scale genomic resources from biobank sequencing projects are crucial for understanding the interplay between environmental and genetic factors in human disease health traits, as well reconstructing evolutionary history. We summarize recent advances cohorts highlight opportunities non-Eurocentric populations a multidisciplinary perspective. Initiatives like UK100K, All of Us, TOPMed precision medicine programs have shifted research paradigms problem-derived to data-driven approaches, enhancing our architecture diseases Europeans their descendants. However, biases persist, such Han bias Chinese focused on medical anthropological purposes. These contribute global inequalities disparities medicine. Evolutionary studies modern ancient genomes provide new insights into history adaptive trajectories critical mutations. findings underscore importance personal genome tailored ethnolinguistically genetically diverse populations. This strategy is vital assessing burden etiology disease. Our work emphasizes need include underrepresented diversity create comprehensive catalog variations understand biological implications.</p>

Language: Английский

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Professionalism vs. engagement: quality of SSc information on WeChat

Frontiers in Public Health, Journal Year: 2025, Volume and Issue: 13

Published: May 14, 2025

Systemic sclerosis (SSc) is a rare autoimmune disease, and WeChat major source of health information in China. This study assesses the quality SSc on to understand its impact public knowledge engagement. A total 375 articles from 9 accounts were systematically analyzed using DISCERN Global Quality Scale (GQS) tools. Article was evaluated based credibility, content accuracy, user engagement, including metrics such as views, likes, comments. Individual authors posted 50% articles, while non-profit organizations 21%, with non-profits providing higher content. Disease dominated (52.8%), yet readers showed interest policy interpretation rehabilitation. The average GQS scores 28.96 1.62, indicating low across articles. While facilitates dissemination, overall lacking. Enhancing professionalism interactivity platforms like could better meet needs patients for reliable information.

Language: Английский

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Paternal genomic resources from the YanHuang cohort suggested a Weakly-Differentiated Multi-source Admixture model for the formation of Han’s founding ancestral lineages

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 13, 2023

Abstract The large-scale human genome revolution and rapidly advanced statistical innovation have updated our understanding of the fine-scale complex genetic structure, entire landscape diversity evolutionary trajectories spatiotemporally different ancients ethnolinguistically diverse modern populations. Recent ancient DNA research provided a detailed admixture picture Europeans but limited insights into East Asians as few available genomes. Y-chromosome variations in male-specific regions, served molecular archaeological tool, unique features that can be utilized to reconstruct origin subsequent interaction Asian paternal lineages. We launched YanHuang cohort using designed highest-resolution capture sequencing panel explore trajectory Han Chinese, one largest ethnic groups world. reported uniparental genomic resources observed multiple founding lineages dominant western Eurasian, Siberian participating formation gene pool Chinese. identified structure correlated with patterns population geographical mountain barriers (Qinling-Huaihe line Nanling Mountains), suggesting isolation-enhanced admixture-introduced differentiation enhanced complexity Chinese diversity. strong direct correlation between frequency proportion subsistence-related ancestry sources related pastoralists, Holocene Mongolian Plateau people Asians, reflecting migration events contributed finally novel most plausible admixture-by-admixture model, Weakly-Differentiated Multi-Source Admixture major mechanism illuminate pattern interactions ancestral Generally, we presented resource from cohort, portrayed model herders, hunter-gatherers farmers who participated

Language: Английский

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The design and implementation of natural population cohort study Biobank: A multiple-center project cooperation with medical consortia in Southwest China

Frontiers in Public Health, Journal Year: 2022, Volume and Issue: 10

Published: Dec. 1, 2022

Objective The West China Hospital of Sichuan University collaborated with regional medical consortia in Province to launch a natural population cohort study (NPCS) investigate the health status residents and collect public data southwest China. Methods Up 80,000 participants will be enrolled by NPCS from 11 over five years. Individuals are invited visit one participating fill out questionnaires, receive free exam, donate biospecimens upon enrolment. All facilities adhered standard operating procedures for collecting processing ensure uniformity (serum, lithium heparinized plasma, ethylene diamine tetraacetie acid buffy coat). Electronic Data Capture System, Picture Archiving Communication Laboratory Information Management Biospecimen Quality Control Biobank used sort classify clinical indices, imaging data, laboratory parameters, pre-analytical variables, biospecimen information, respectively. quality assurance control biobank “DAIDS Guidelines Good Clinical Practice Standards”. This project integrate high-dimensional multi-omics questionnaire environmental risk factors. Results An estimated 2,240,000 aliquots sample stored end study. These samples linked comprehensively collected parameters. Big analysis can implemented create predictive algorithms, explore pathogenesis mechanisms, uncover potential biomarkers, provide information on health. Conclusions an integrative approach research factors major chronic or endemic diseases key scientific evidence support formulation management policies

Language: Английский

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Integrating genomics and proteomics data to identify candidate plasma biomarkers for lung cancer risk among European descendants

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(9), P. 1510 - 1515

Published: Sept. 7, 2023

Language: Английский

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BRCA2 mutation in advanced lung squamous cell carcinoma treated with Olaparib and a PD-1 inhibitor: a case report

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: May 16, 2023

Background Mutations in the human breast cancer susceptibility gene 2 (breast 2, BRCA2) increase risk of breast, ovarian and other cancers. Olaparib, an oral poly[adenosine diphosphate (ADP)–ribose] polymerase (PARP) inhibitor, is usually prescribed to treat BRCA mutated tumors, especially Programmed cell death-1 (PD-1) inhibitors have revolutionized treatment lung many cancers by destroying interaction between receptors with ligands tumor-immune microenvironment enabling T cells recognize attack cells. Case description In our study, we report a patient advanced BRCA2 squamous carcinoma who received platinum-based chemotherapy combined paclitaxel. Seven months later, disease progressed. mutations were detected peripheral blood next-generation sequencing. After Olaparib Cindilimab, was partial remission progression-free survival (PFS) lasted for 6 months, but developed immune renal damage. Conclusions This study adds clinical data mutant non-small demonstrating that has good response PARP inhibitors. It also serves as reminder there may still be some negative effects from targeted superimposed immunotherapy.

Language: Английский

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Current status of molecular diagnostics for lung cancer

Exploration of Targeted Anti-tumor Therapy, Journal Year: 2024, Volume and Issue: 5(3), P. 742 - 765

Published: June 27, 2024

The management of lung cancer (LC) requires the analysis a diverse spectrum molecular targets, including kinase activating mutations in EGFR, ERBB2 (HER2), BRAF and MET oncogenes, KRAS G12C substitutions, ALK, ROS1, RET NTRK1-3 gene fusions. Administration immune checkpoint inhibitors (ICIs) is based on immunohistochemical (IHC) PD-L1 expression determination tumor mutation burden (TMB). Clinical characteristics patients, particularly age, gender smoking history, significantly influence probability finding above targets: for example, LC young patients characterized by high frequency rearrangements, while heavy smokers often have and/or TMB. Proper selection first-line therapy influences overall treatment outcomes, therefore, majority these tests need to be completed within no more than 10 working days. Activating events MAPK signaling pathway are mutually exclusive, hence, fast single-gene testing remains an option some laboratories. RNA next-generation sequencing (NGS) capable detecting entire repertoire druggable alterations, therefore it gradually becoming dominating technology diagnosis.

Language: Английский

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