ArticleNature genetics2025
Whole-genome sequencing analysis identifies rare, large-effect noncoding variants and regulatory regions associated with circulating protein levels.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- AlphaGenome Atlas:medRxiv : the preprint server for health sciences · 2026Article
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- Massively parallel characterization and predictive modelling of neuronal regulatory variation.bioRxiv : the preprint server for biology · 2026Article
- Whole-genome sequencing implicates rare, low-frequency and structural non-coding variation at themedRxiv : the preprint server for health sciences · 2026Article
- UK Biobank whole-genome sequencing reveals robust contributions of rare variants to complex-trait heritability.Genome biology · 2026Article
- Characterisation of the SMN1/2 locus using a highly specific variant caller on whole-genome sequence data from 500,000 individuals.European journal of human genetics : EJHG · 2026Article
- Analysis of whole genome sequencing and plasma metabolomics unveil genetic determinants and clinical implications for human health.Nature communications · 2026Article
- Sex-differential associations of MC3R p.F45S with human metabolic profile.Journal of neuroendocrinology · 2026Article
- DBCL-DFNet: Dual-Branch Contrastive Learning for Multi-Omics Dynamic Fusion.Entropy (Basel, Switzerland) · 2026Article
- Genome-wide detection of human 5' UTR variants that impact protein translation.American journal of human genetics · 2026Article
- Rare coding and noncoding variants map 1,342 diseases and biomarkers in 490,549 whole genomes.medRxiv : the preprint server for health sciences · 2026Article
- Scalable and accurate rare-variant association tests for whole genome sequencing time-to-event analysis in large biobanks.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations.Nature communications · 2026Article
- Article
- Beyond the Exome: The Role of Noncoding and Regulatory Variants in Monogenic Diseases.Current issues in molecular biology · 2025Review
- Clinical utility of genome sequencing in rare diseases: lessons from a single-center study of 1,452 Korean families.NPJ genomic medicine · 2025Article
- Towards improved fine-mapping of candidate causal variants.Nature reviews. Genetics · 2025Review
- Genome region aware CADD thresholds for noncoding variant prioritization.NAR genomics and bioinformatics · 2025Article
- Noncoding rare variant associations with blood traits in 166,740 UK Biobank genomes.Nature genetics · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The contribution of rare noncoding genetic variation to common phenotypes is largely unknown, as a result of a historical lack of population-scale whole-genome sequencing data and the difficulty of categorizing noncoding variants into functionally similar groups. To begin addressing these challenges, we performed a cis association analysis using whole-genome sequencing data, consisting of 1.1 billion variants, 123 million noncoding aggregate-based tests and 2,907 circulating protein levels in ~50,000 UK Biobank participants. We identified 604 independent rare noncoding single-variant associations with circulating protein levels. Unlike protein-coding variation, rare noncoding genetic variation was almost as likely to increase or decrease protein levels. Rare noncoding aggregate testing identified 357 conditionally independent associated regions. Of these, 74 (21%) were not detectable by single-variant testing alone. Our findings have important implications for the identification, and role, of rare noncoding genetic variation associated with common human phenotypes, including the importance of testing aggregates of noncoding variants.
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