ArticleNature genetics2018
Functional architecture of low-frequency variants highlights strength of negative selection across coding and non-coding annotations.
Article in Nature genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
124 citing papers in PubMed, 8 syntheses or guidelines pooled it.
- Multi-ancestry genome-wide association analyses of refractive error augment genetic discovery and polygenic prediction.Nature genetics · 2026Pooled it
- Genetic landscape and functional exploration of kidney cancer predisposition in cross-ancestral populations.Nature communications · 2026Pooled it
- Cross-ancestry genome-wide association studies of liver function biomarkers uncover pleiotropic variants, systemic disease links and therapeutic targets.Genome medicine · 2026Pooled it
- Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.Nature communications · 2023Pooled it
- Genome-Wide Association Study on Longitudinal Change in Fasting Plasma Glucose in Korean Population.Diabetes & metabolism journal · 2023Pooled it
- Population-scale analysis of common and rare genetic variation associated with hearing loss in adults.Communications biology · 2022Pooled it
- Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss.American journal of human genetics · 2022Pooled it
- Incorporating functional priors improves polygenic prediction accuracy in UK Biobank and 23andMe data sets.Nature communications · 2021Pooled it
- Identifying independent causal cell types for human diseases and risk variants.Cell genomics · 2026Article
- Correlations between causal effect sizes of proximal SNPs vary with functional annotations and implicate stabilizing selection.Nature genetics · 2026Article
- Evolution of quantitative traits with background selection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Improved heritability partitioning and enrichment analyses using summary statistics with graphREML.Nature genetics · 2026Article
- An empirical Bayes framework for burden and dispersion association tests helps prioritize rare variants associated with Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Analysis of whole genome sequencing and plasma metabolomics unveil genetic determinants and clinical implications for human health.Nature communications · 2026Article
- Fine-mapping candidate neuropsychiatric regulatory variants using cell type-aware comparative genomics.bioRxiv : the preprint server for biology · 2026Article
- A dish-to-biobank framework links β-cell nutrient-stress programs to genetic and dietary risk for Type 2 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- Pleiotropic shared heritability quantifies the shared genetic variance of common diseases.Nature genetics · 2026Article
- Decoding sequence determinants of gene expression in diverse cellular and disease states.Nature methods · 2026Article
- Mapping disease loci to biological processes via joint pleiotropic and epigenomic partitioning.Cell genomics · 2026Article
- Background selection in recombining genomes and its consequences for the maintenance of variation in complex traits.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Common variant heritability has been widely reported to be concentrated in variants within cell-type-specific non-coding functional annotations, but little is known about low-frequency variant functional architectures. We partitioned the heritability of both low-frequency (0.5%≤ minor allele frequency <5%) and common (minor allele frequency ≥5%) variants in 40 UK Biobank traits across a broad set of functional annotations. We determined that non-synonymous coding variants explain 17 ± 1% of low-frequency variant heritability ([Formula: see text]) versus 2.1 ± 0.2% of common variant heritability ([Formula: see text]). Cell-type-specific non-coding annotations that were significantly enriched for [Formula: see text] of corresponding traits were similarly enriched for [Formula: see text] for most traits, but more enriched for brain-related annotations and traits. For example, H3K4me3 marks in brain dorsolateral prefrontal cortex explain 57 ± 12% of [Formula: see text] versus 12 ± 2% of [Formula: see text] for neuroticism. Forward simulations confirmed that low-frequency variant enrichment depends on the mean selection coefficient of causal variants in the annotation, and can be used to predict effect size variance of causal rare variants (minor allele frequency <0.5%).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.