ArticlePLoS genetics2017
Rare coding variants pinpoint genes that control human hematological traits.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians.Nature communications · 2022Pooled it
- A large-scale exome array analysis of venous thromboembolism.Genetic epidemiology · 2019Pooled it
- Evolutionary history of disease-susceptibility loci identified in longitudinal exome-wide association studies.Molecular genetics & genomic medicine · 2019Trial
- Structural and functional consequences of IL33 and IL1RL1 coding variants on IL-33/ST2 signaling.Genes and immunity · 2026Article
- Article
- Comprehensive gene heritability estimation reveals the genetic architecture of rare coding variants underlying complex traits.bioRxiv : the preprint server for biology · 2025Article
- Red Blood Cell-Related Phenotype-Genotype Correlations in Chronic and Acute Critical Illnesses (Traumatic Brain Injury Cohort and COVID-19 Cohort).International journal of molecular sciences · 2025Article
- A genome-wide association study of neutrophil count in individuals associated to an African continental ancestry group facilitates studies of malaria pathogenesis.Human genomics · 2024Article
- Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma.The Journal of allergy and clinical immunology · 2024Article
- Plasminogen missense variants and their involvement in cardiovascular and inflammatory disease.Frontiers in cardiovascular medicine · 2024Review
- BIGKnock: fine-mapping gene-based associations via knockoff analysis of biobank-scale data.Genome biology · 2023Article
- Review
- Whole genome sequence analysis of platelet traits in the NHLBI Trans-Omics for Precision Medicine (TOPMed) initiative.Human molecular genetics · 2022Article
- From musk to body odor: Decoding olfaction through genetic variation.PLoS genetics · 2022Article
- eSCAN: scan regulatory regions for aggregate association testing using whole-genome sequencing data.Briefings in bioinformatics · 2022Article
- An Asian-specific MPL genetic variant alters JAK-STAT signaling and influences platelet count in the population.Human molecular genetics · 2021Article
- Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program.American journal of human genetics · 2021Article
- Genetic Influence on Frequencies of Myeloid-Derived Cell Subpopulations in Mouse.Frontiers in immunology · 2021Article
- Heterozygous germ line CSF3R variants as risk alleles for development of hematologic malignancies.Blood advances · 2020Article
- Integrative Genomic Analysis Reveals Four Protein Biomarkers for Platelet Traits.Circulation research · 2020Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
The identification of rare coding or splice site variants remains the most straightforward strategy to link genes with human phenotypes. Here, we analyzed the association between 137,086 rare (minor allele frequency (MAF) <1%) coding or splice site variants and 15 hematological traits in up to 308,572 participants. We found 56 such rare coding or splice site variants at P<5x10-8, including 31 that are associated with a blood-cell phenotype for the first time. All but one of these 31 new independent variants map to loci previously implicated in hematopoiesis by genome-wide association studies (GWAS). This includes a rare splice acceptor variant (rs146597587, MAF = 0.5%) in interleukin 33 (IL33) associated with reduced eosinophil count (P = 2.4x10-23), and lower risk of asthma (P = 2.6x10-7, odds ratio [95% confidence interval] = 0.56 [0.45-0.70]) and allergic rhinitis (P = 4.2x10-4, odds ratio = 0.55 [0.39-0.76]). The single new locus identified in our study is defined by a rare p.Arg172Gly missense variant (rs145535174, MAF = 0.05%) in plasminogen (PLG) associated with increased platelet count (P = 6.8x10-9), and decreased D-dimer concentration (P = 0.018) and platelet reactivity (P<0.03). Finally, our results indicate that searching for rare coding or splice site variants in very large sample sizes can help prioritize causal genes at many GWAS loci associated with complex human diseases and traits.
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