Leveraging genome‐wide association studies to better understand the etiology of cancers DOI Creative Commons
Kyuto Sonehara, Yukinori Okada

Cancer Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

Abstract Genome‐wide association studies (GWAS) statistically assess the between tens of millions genetic variants in whole genome and a phenotype interest. enable elucidation polygenic inheritance cancer, which myriad low‐penetrance collectively contribute to substantial proportion heritable susceptibility. In addition robust genotype–phenotype associations provided by GWAS, combining GWAS data with functional genomic datasets or sophisticated statistical methods unlocks deeper insights. Integrating genotype molecular phenotyping facilitates characterization signals through quantitative trait loci mapping transcriptome‐wide studies. Furthermore, aggregating genome‐wide signals, including subthreshold associations, enables one estimate correlations across diverse phenotypes helps clinical risk predictions evaluating scores. this review, we begin summarizing rationale for introduce recent methodological updates GWAS‐derived downstream analyses, demonstrate their applications cancers.

Language: Английский

Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder DOI Creative Commons

Tomohiro Yata,

Go Sato, Kotaro Ogawa

et al.

Cell Genomics, Journal Year: 2025, Volume and Issue: unknown, P. 100776 - 100776

Published: Feb. 1, 2025

Language: Английский

Citations

0
Germline variants and mosaic chromosomal alterations affect COVID-19 vaccine immunogenicity DOI Creative Commons
Kyuto Sonehara, Yoshifumi Uwamino, Ryunosuke Saiki

et al.

Cell Genomics, Journal Year: 2025, Volume and Issue: unknown, P. 100783 - 100783

Published: March 1, 2025

Vaccine immunogenicity is influenced by the vaccinee's genetic background. Here, we perform a genome-wide association study of vaccine-induced SARS-CoV-2-specific immunoglobulin G (IgG) antibody titers and T cell immune responses in 1,559 mRNA-1273 537 BNT162b2 vaccinees Japanese ancestry. are associated with heavy chain (IGH) major histocompatibility complex (MHC) locus, MHC. The lead variants at IGH contain population-specific missense variant (rs1043109-C; p.Leu192Val) constant gamma 1 gene (IGHG1), strong decreasing effect (β = -0.54). Antibody-titer-associated modulate circulating regulatory proteins (e.g., LILRB4 FCRL6). Age-related hematopoietic expanded mosaic chromosomal alterations (mCAs) affecting MHC also impair production. MHC-/IGH-affecting mCAs confer infectious disease risk, including sepsis Graves' disease. Impacts loss chromosomes X/Y on these phenotypes were examined. Altogether, both germline somatic mutations contribute to adaptive immunity functions.

Language: Английский

Citations

0
ABO blood group and COVID-19 severity: Associations with endothelial and adipocyte activation in critically ill patients DOI Creative Commons
Sophie Stukas, George Goshua, Edward M. Conway

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0320251 - e0320251

Published: April 2, 2025

Background ABO blood group has been implicated both in susceptibility to, and severity of, SARS-CoV-2 infection. The aim of this study was to explore a potential association between COVID-19 infection critically ill patients the following biological mechanisms: inflammatory cytokines, endothelial injury, adipokines. Methods We conducted retrospective 128 admitted Vancouver General Hospital from March 2020-March 2021. Outcomes including 28-day mortality, need for mechanical ventilation length intensive care unit (ICU) stay were compared with A & AB type vs. B O type. Likewise, serum markers, markers activation, adipokines compared. Results disease confirmed. Patients A&AB had more frequent requirements B&O (N(%): 35 (71%) vs 41 (52%), p = 0.041), higher total ICU mortality (14 (29%) 9 (11%), 0.018), longer median (days, [interquartile range]: 10 [6-19], 7 [3-14], 0.016) hospital (26 [14-36] 17 [10-30] 0.034). No found cytokines or their receptors [IL-6, IL-1b, IL-10, TNF, sIL-6R, sgp130] measured within first days stay. plasma injury [Thrombomodulin, ADAMTS13, sP-Selectin, Factor IX, Protein C, S, vWF]. Among adipokines, there no differences lipocalin-2, PAI-1 resistin. Notably, however, adipsin O&B (16.3 [4.2-38.5] x10 6 pg/mL 9.61 [3.0-20.8] x pg/mL, 0.048). Conclusions This single-center confirms an severe COVID-19. While underlying mechanism not identified, finding levels A/AB warrants further investigation larger prospective studies.

Language: Английский

Citations

0
Ancestry diversity in the genetic determinants of the human plasma proteome and associated new drug targets DOI Creative Commons
Alfred Pozarickij,

Saredo Said,

Kuang Lin

et al.

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

Published: Nov. 13, 2023

Abstract The proteome is fundamental to human biology and health but little known about ancestral diversity of its genetic determinants. In GWAS plasma levels 2,923 proteins in 3,974 Chinese adults, we identified pQTLs for 1,784 proteins, including 1,312 cis -pQTLs 1,264 proteins. Fine-mapping 3,475 credible sets independent pQTLs, 36% which were distinct from those European adults as assessed by three different methods. phenome-wide MR analyses, 59 disease associations strong LD (r 2 >0.95) with a -pQTL sentinel variant, 26 evidence colocalisation (PP.H4>0.9) 34 not previous similar studies. Evaluation current drug development 8 confirmed therapeutic targets, potential repurposing 19 novel targets (13 previously reported Europeans). findings demonstrate the importance extending proteogenomic studies non-European ancestry populations identify major diseases.

Language: Английский

Citations

6
Leveraging genome‐wide association studies to better understand the etiology of cancers DOI Creative Commons
Kyuto Sonehara, Yukinori Okada

Cancer Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

Abstract Genome‐wide association studies (GWAS) statistically assess the between tens of millions genetic variants in whole genome and a phenotype interest. enable elucidation polygenic inheritance cancer, which myriad low‐penetrance collectively contribute to substantial proportion heritable susceptibility. In addition robust genotype–phenotype associations provided by GWAS, combining GWAS data with functional genomic datasets or sophisticated statistical methods unlocks deeper insights. Integrating genotype molecular phenotyping facilitates characterization signals through quantitative trait loci mapping transcriptome‐wide studies. Furthermore, aggregating genome‐wide signals, including subthreshold associations, enables one estimate correlations across diverse phenotypes helps clinical risk predictions evaluating scores. this review, we begin summarizing rationale for introduce recent methodological updates GWAS‐derived downstream analyses, demonstrate their applications cancers.

Language: Английский

Citations

1