ArticleEuropean journal of human genetics : EJHG2017
Missing heritability: is the gap closing? An analysis of 32 complex traits in the Lifelines Cohort Study.
Article in European journal of human genetics : EJHG, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 4 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Genetic insights into resting heart rate and its role in cardiovascular disease.Nature communications · 2023Pooled it
- X-linked genes influence various complex traits in dairy cattle.BMC genomics · 2023Pooled it
- Kernel-based gene-environment interaction tests for rare variants with multiple quantitative phenotypes.PloS one · 2022Pooled it
- Genetic loci associated with heart rate variability and their effects on cardiac disease risk.Nature communications · 2017Pooled it
- Polygenic Risk Scores Predicting Estimated GFR Validated With Iohexol Clearance.Kidney international reports · 2026Article
- Gene expression variation across genetically identical individuals predicts reproductive traits.eLife · 2025Article
- Addressing overfitting bias due to sample overlap in polygenic risk scoring.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Evaluation of Polygenic Risk Score for Prediction of Childhood Onset and Severity of Asthma.International journal of molecular sciences · 2024Article
- Transcriptome-Wide Association Study Reveals Potentially Candidate Genes Responsible for Milk Production Traits in Buffalo.International journal of molecular sciences · 2024Article
- Incorporating functional annotation with bilevel continuous shrinkage for polygenic risk prediction.BMC bioinformatics · 2024Article
- kGWASflow: a modular, flexible, and reproducible Snakemake workflow for k-mers-based GWAS.G3 (Bethesda, Md.) · 2023Article
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- CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.Cell genomics · 2022Article
- Explainable deep transfer learning model for disease risk prediction using high-dimensional genomic data.PLoS computational biology · 2022Article
- An eco-evo-devo genetic network model of stress response.Horticulture research · 2022Article
- Genetic association-based functional analysis detectsFrontiers in genetics · 2022Article
- Decoding 'Unnecessary Complexity': A Law of Complexity and a Concept of Hidden Variation Behind "Missing Heritability" in Precision Medicine.Journal of molecular evolution · 2021Review
- The trans-ancestral genomic architecture of glycemic traits.Nature genetics · 2021Article
- Genetic analyses identify widespread sex-differential participation bias.Nature genetics · 2021Article
- Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.Nature genetics · 2021Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the recent explosive rise in number of genetic markers for complex disease traits identified in genome-wide association studies, there is still a large gap between the known heritability of these traits and the part explained by these markers. To gauge whether this 'heritability gap' is closing, we first identified genome-wide significant SNPs from the literature and performed replication analyses for 32 highly relevant traits from five broad disease areas in 13 436 subjects of the Lifelines Cohort. Next, we calculated the variance explained by multi-SNP genetic risk scores (GRSs) for each trait, and compared it to their broad- and narrow-sense heritabilities captured by all common SNPs. The majority of all previously-associated SNPs (median=75%) were significantly associated with their respective traits. All GRSs were significant, with unweighted GRSs generally explaining less phenotypic variance than weighted GRSs, for which the explained variance was highest for height (15.5%) and varied between 0.02 and 6.7% for the other traits. Broad-sense common-SNP heritability estimates were significant for all traits, with the additive effect of common SNPs explaining 48.9% of the variance for height and between 5.6 and 39.2% for the other traits. Dominance effects were uniformly small (0-1.5%) and not significant. On average, the variance explained by the weighted GRSs accounted for only 10.7% of the common-SNP heritability of the 32 traits. These results indicate that GRSs may not yet be ready for accurate personalized prediction of complex disease traits limiting widespread adoption in clinical practice.
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