Expressive

rs11841319 - IRS2 - RN7SKP10

Magnitude 2.2 · 8 studies on file

Reported associations

  • Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia. - American journal of human genetics (2021) · Kachuri L, Jeon S, DeWan AT, Metayer C, Ma X, Witte JS, Chiang CWK, Wiemels JL, de Smith AJ · PubMed 34469753

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Despite overlap between genetic risk loci for ALL and hematologic traits, the etiological relevance of dysregulated blood-cell homeostasis remains unclear. We investigated this question in a genome-wide association study (GWAS) of childhood ALL (2,666 affected individuals, 60,272 control individuals) and a multi-trait GWAS of nine blood-cell indices in the UK Biobank. We identified 3,000 blood-cell-trait-associated (p < 5.0 × 10 ) variants, explaining 4.0% to 23.9% of trait variation and including 115 loci associated with blood-cell ratios (LMR, lymphocyte-to-monocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio). ALL susceptibility was genetically correlated with lymphocyte counts (r

  • Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program - Unknown journal (n.d.) · Unknown authors · PubMed 39024449

    ABSTRACT: INTRODUCTION: Findings from genome-wide association studies (GWASs) have provided foundational knowledge of the genetic basis of disease, facilitating precision approaches for prevention and treatment. Current GWAS results are limited by underrepresentation of individuals from diverse populations, leading to concerns with generalizability regarding our knowledge of the relationships between genes, traits, and disease. The Department of Veterans Affairs (VA) Million Veteran Program (MVP), one of the largest US-based biobanks, addresses this need; 29% of MVP comprises individuals genetically similar to African (AFR), Admixed American (AMR), and East Asian (EAS) reference populations. With over 635,000 participants and more than 44.3M genotyped variants linked with detailed phenotyp

  • Trans-ethnic and ancestry-specific blood-cell genetics in 746,667 individuals from 5 global populations - Unknown journal (n.d.) · Unknown authors · PubMed 32888493

    ABSTRACT: SUMMARY Most loci identified by GWAS have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at P<5×10−9, including 71 novel loci not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional, and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value

  • A scalable variational inference approach for increased mixed-model association power - Unknown journal (n.d.) · Unknown authors · PubMed 39789286

    ABSTRACT: The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing the benefits of large-scale data collection efforts. We developed Quickdraws, a method that increases association power in quantitative and binary traits without sacrificing computational efficiency, leveraging a spike-and-slab prior on variant effects, stochastic variational inference and graphics processing unit acceleration. We applied Quickdraws to 79 quantitative and 50 binary traits in 405,088 UK Biobank samples, identifying 4.97% and 3.25% more associations than REGENIE and 22.71%

  • Phenome-wide analysis of Taiwan Biobank reveals novel glycemia-related loci and genetic risks for diabetes - Unknown journal (n.d.) · Unknown authors · PubMed 36329257

    ABSTRACT: To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA1c) was performed and identified 115 significant loci with four novel genetic variants (HACL1, RAD21, ASH1L and GAK). Transcriptomics data also strengthen the relevancy of the findings to metabolic disorders, thus contributing to better understanding of pathogenesis. In addition, genetic risk sc

  • Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures - Unknown journal (n.d.) · Unknown authors · PubMed 40436827

    ABSTRACT: Genome-wide association studies (GWAS) have predominantly focused on European ancestry populations, limiting biological discoveries across diverse populations. Here we report GWAS findings from 153,950 individuals across 36 quantitative traits in the Korean Cancer Prevention Study-II (KCPS2) Biobank. We discovered 301 previously unreported genetic loci in KCPS2, including an association between thyroid-stimulating hormone and CD36. Meta-analysis with the Korean Genome and Epidemiology Study, Biobank Japan, Taiwan Biobank, and UK Biobank identified 4588 loci that were not significant in any contributing GWAS. We describe differences in genetic architectures across these East Asian and European samples. We also highlight East Asian specific associations, including a known pleiotrop

  • Multi-trait GWAS for diverse ancestries: mapping the knowledge gap - Unknown journal (n.d.) · Unknown authors · PubMed 38627641

    ABSTRACT: Background Approximately 95% of samples analyzed in univariate genome-wide association studies (GWAS) are of European ancestry. This bias toward European ancestry populations in association screening also exists for other analyses and methods that are often developed and tested on European ancestry only. However, existing data in non-European populations, which are often of modest sample size, could benefit from innovative approaches as recently illustrated in the context of polygenic risk scores. Methods Here, we extend and assess the potential limitations and gains of our multi-trait GWAS pipeline, JASS (Joint Analysis of Summary Statistics), for the analysis of non-European ancestries. To this end, we conducted the joint GWAS of 19 hematological traits and glycemic traits acro

  • The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease - Unknown journal (n.d.) · Unknown authors · PubMed 27863252

    ABSTRACT: Summary Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we

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