Trait selection strategy in multi-trait GWAS: Boosting SNPs discoverability DOI Creative Commons
Yuka Suzuki, Hervé Ménager, Bryan Brancotte

et al.

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

Published: Oct. 27, 2023

Since the first Genome-Wide Association Studies (GWAS), thousands of variant-trait associations have been discovered. However, sample size required to detect additional variants using standard univariate association screening is increasingly prohibitive. Multi-trait GWAS offers a relevant alternative: it can improve statistical power and lead new insights about gene function joint genetic architecture human phenotypes. Although many methodological hurdles multi-trait testing discussed, strategy select trait, among overwhelming possibilities, has overlooked. In this study, we conducted extensive tests JASS (Joint Analysis Summary Statistics) assessed which features analysed sets were associated with an increased detection as compared screening. Our analyses identified multiple factors gain in tests. Together, these are predictive test (Pearson's ρ equal 0.43 between observed predicted gain, P < 1.6 × 10-60). Applying alternative approach (MTAG, analysis GWAS), found that most scenarios but particularly those larger numbers traits, outperformed MTAG. Finally, benchmark several strategies set traits including prevalent selecting clinically similar systematically underperformed heterogenous or issued from our data-driven models. This work provides unique picture determinant outline practical for testing.

Language: Английский

Spotlight on amino acid changing mutations in the JAK-STAT pathway: from disease-specific mutation to general mutation databases DOI Creative Commons
Markus Hoffmann, Lothar Hennighausen

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 20, 2025

The JAK-STAT pathway is central to cytokine signaling and controls normal physiology disease. Aberrant activation via mutations that change amino acids in proteins of the can result diseases. While disease-centric databases like COSMIC catalog cancer, their prevalence healthy populations remains underexplored. We systematically studied such genes by comparing population-focused All Us database. Our analysis revealed frequent all JAK STAT domains, particularly among white females. further identified three categories: Mutations uniquely found were associated with cancer literature but could not be COSMIC, underscoring COSMIC's limitations. unique underline potential as drivers due absence general population. present both databases, e.g., JAK2Val617Phe/V617F - widely recognized a driver hematopoietic cells, without disease associations Us, raising possibility combinatorial SNPs might responsible for development. These findings illustrate complementarity understanding mutation impacts underscore need multi-mutation analyses uncover genetic factors underlying complex diseases advance personalized medicine.

Language: Английский

Citations

0
The expanding global genomics landscape: Converging priorities from national genomics programs DOI Creative Commons

Caitlin Howley,

Matilda Haas,

Wadha A. Al Muftah

et al.

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

SummaryThe global landscape of health genomics is expanding rapidly, with an increasing number national and international initiatives, many which are targeted toward accelerating the clinical implementation genomic technologies services in context local systems. This includes a range entities different levels maturity, funding sources, strategies that focus on research priorities to varying degrees. While there no "one-size-fits-all" approach, analysis programs helps identify common priority areas, barriers, enablers. Here, we synthesize converging several highlight importance progressing scale.Graphical abstract

Language: Английский

Citations

0
Genome-wide association mapping of scuticociliatosis resistance in a vaccinated population of olive flounder (Paralichthys olivaceus) DOI
Yasara Kavindi Kodagoda, Gaeun Kim,

D.S. Liyanage

et al.

Fish & Shellfish Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 110339 - 110339

Published: April 1, 2025

Language: Английский

Citations

0
Cross-ancestry meta-genome-wide association studies provide insights to the understanding of semen traits in pigs DOI Creative Commons
Hong Cheng, Zhiyuan Zhang,

H. Han

et al.

animal, Journal Year: 2024, Volume and Issue: 18(11), P. 101331 - 101331

Published: Sept. 19, 2024

Language: Английский

Citations

3
Genetic Inheritance Models of Non-Syndromic Cleft Lip with or without Palate: From Monogenic to Polygenic DOI Open Access
Xi Cheng,

Fengzhou Du,

Xiao Long

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(10), P. 1859 - 1859

Published: Sept. 24, 2023

Non-syndromic cleft lip with or without palate (NSCL/P) is a prevalent birth defect that affects 1/500–1/1400 live births globally. The genetic basis of NSCL/P intricate and involves both environmental factors. In the past few years, various inheritance models have been proposed to elucidate underlying mechanisms NSCL/P. These range from simple monogenic more complex polygenic inheritance. Here, we present comprehensive overview model exemplified by representative genes regions perspectives. We also summarize existing association studies corresponding loci within Chinese population highlight potential utilizing risk scores for stratification application offers promising avenues improved assessment personalized approaches in prevention management individuals.

Language: Английский

Citations

5
Trait selection strategy in multi-trait GWAS: Boosting SNP discoverability DOI Creative Commons
Yuka Suzuki, Hervé Ménager,

Bryan Brancotte

et al.

Human Genetics and Genomics Advances, Journal Year: 2024, Volume and Issue: 5(3), P. 100319 - 100319

Published: June 13, 2024

Language: Английский

Citations

1
Trait selection strategy in multi-trait GWAS: Boosting SNPs discoverability DOI Creative Commons
Yuka Suzuki, Hervé Ménager, Bryan Brancotte

et al.

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

Published: Oct. 27, 2023

Since the first Genome-Wide Association Studies (GWAS), thousands of variant-trait associations have been discovered. However, sample size required to detect additional variants using standard univariate association screening is increasingly prohibitive. Multi-trait GWAS offers a relevant alternative: it can improve statistical power and lead new insights about gene function joint genetic architecture human phenotypes. Although many methodological hurdles multi-trait testing discussed, strategy select trait, among overwhelming possibilities, has overlooked. In this study, we conducted extensive tests JASS (Joint Analysis Summary Statistics) assessed which features analysed sets were associated with an increased detection as compared screening. Our analyses identified multiple factors gain in tests. Together, these are predictive test (Pearson's ρ equal 0.43 between observed predicted gain, P < 1.6 × 10-60). Applying alternative approach (MTAG, analysis GWAS), found that most scenarios but particularly those larger numbers traits, outperformed MTAG. Finally, benchmark several strategies set traits including prevalent selecting clinically similar systematically underperformed heterogenous or issued from our data-driven models. This work provides unique picture determinant outline practical for testing.

Language: Английский

Citations

1