ArticleNature communications2022
Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- UK Biobank whole-genome sequencing reveals robust contributions of rare variants to complex-trait heritability.Genome biology · 2026Article
- Genetic regulation of the plasma proteome and its link to cardiometabolic disease in Greenlandic Inuit.American journal of human genetics · 2025Article
- Severity of effect considerations regarding the use of mutation as a toxicological endpoint for risk assessment: A report from the 8th International Workshop on Genotoxicity Testing (IWGT).Environmental and molecular mutagenesis · 2025Review
- T2T-CHM13 improves read mapping and detection of clinically relevant genetic variation in the Swedish population.Genome research · 2025Article
- Multi-omics approaches for understanding gene-environment interactions in noncommunicable diseases: techniques, translation, and equity issues.Human genomics · 2025Review
- A modeling of complex trait phenotypic variance determinants.PNAS nexus · 2024Article
- Venous thromboembolic disease genetics: from variants to function.Journal of thrombosis and haemostasis : JTH · 2024Review
- GWAS advancements to investigate disease associations and biological mechanisms.Clinical and translational discovery · 2024Article
- Genetic determinants of plasma protein levels in the Estonian population.Scientific reports · 2024Article
- Article
- Gene expression and RNA splicing explain large proportions of the heritability for complex traits in cattle.Cell genomics · 2023Article
- The complete and fully-phased diploid genome of a male Han Chinese.Cell research · 2023Article
- Article
- Precision medicine in complex diseases-Molecular subgrouping for improved prediction and treatment stratification.Journal of internal medicine · 2023Review
- Unravelling the genetic architecture of human complex traits through whole genome sequencing.Nature communications · 2023Article
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- Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the success of genome-wide association studies, much of the genetic contribution to complex traits remains unexplained. Here, we analyse high coverage whole-genome sequencing data, to evaluate the contribution of rare genetic variants to 414 plasma proteins. The frequency distribution of genetic variants is skewed towards the rare spectrum, and damaging variants are more often rare. We estimate that less than 4.3% of the narrow-sense heritability is expected to be explained by rare variants in our cohort. Using a gene-based approach, we identify Cis-associations for 237 of the proteins, which is slightly more compared to a GWAS (N = 213), and we identify 34 associated loci in Trans. Several associations are driven by rare variants, which have larger effects, on average. We therefore conclude that rare variants could be of importance for precision medicine applications, but have a more limited contribution to the missing heritability of complex diseases.
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