ReviewHuman genetics2020
Missing heritability of complex diseases: case solved?
Review in Human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
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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.
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Who cites it
87 citing papers in PubMed.
- Intragenic deletions from whole genome sequencing of 1054 suicide deaths.Research square · 2026Article
- When splicing is not all or none: GT>GC 5' splice-site variants as a model for intermediate effects and challenges in variant classification.HGG advances · 2026Article
- UK Biobank whole-genome sequencing reveals robust contributions of rare variants to complex-trait heritability.Genome biology · 2026Article
- The Use of Population Isolates to Identify Metabolic Syndrome's Genetic Aetiology.Molecular genetics & genomic medicine · 2026Review
- Harnessing artificial intelligence in plant breeding: innovations in digital phenotyping and breeding methodologies.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2026Review
- Genomic selection accuracy and bias using imputed genotypes on growth, welfare and fitness traits in two Pekin duck lines.BMC genomics · 2026Article
- Interactions between rare variants in DNA repair genes and cardiometabolic risk explain more variability in cognitive function.GeroScience · 2026Article
- Rare variants in FAT3 as possible contributors to non-syndromic orofacial cleft risk.Human genomics · 2026Article
- Association Between Catenin Beta-1 (CTNNB1) Gene Polymorphisms and Non-Traumatic Osteonecrosis of the Femoral Head (ONFH).Current issues in molecular biology · 2026Article
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- Comprehensive benchmarking single and multi ancestry polygenic score methods with the PGS-hub platform.Nature communications · 2026Article
- The Evolution of Gene Sequencing Technologies: Unveiling Genetic Architecture of Nonsyndromic Orofacial Clefts.Genetics research · 2026Review
- Autism Heterogeneity Related to Preterm Birth: Multi-Ancestry Results From the Simons Foundation Powering Autism Research for Knowledge Sample.Biological psychiatry global open science · 2026Article
- Evolvability: progress and key questions.Bioscience · 2025Review
- SPINK1-related chronic pancreatitis: A model that encapsulates the spectrum of variant effects, genetic complexity, and classificatory challenges.American journal of human genetics · 2025Article
- Novel susceptibility gene SLC23A2 functions via PI3K-AKT-mTOR pathway in etiology of non-syndromic cleft palate.Journal of human genetics · 2025Observational
- Systematic benchmarking of tools for structural variation detection using short- and long-read sequencing data in pigs.iScience · 2025Article
- Multi-omics approaches for understanding gene-environment interactions in noncommunicable diseases: techniques, translation, and equity issues.Human genomics · 2025Review
- Whole-exome sequencing association study reveals genetic effects on tumor microenvironment components in nasopharyngeal carcinoma.The Journal of clinical investigation · 2025Article
- Psychiatric neuroimaging at a crossroads: Insights from psychiatric genetics.Developmental cognitive neuroscience · 2024Review
27 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
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
About 10 years ago, after the first large-scale genome-wide association studies (GWAS) were conducted to find genes associated with common complex diseases, investigators were surprised to find that the amount of heritability explained by the significant hits was very low for almost all the studied traits. Indeed, when compared to heritability estimates expected from the observed trait concordance within families, the heritability explained by the associated variants was always much smaller, more than ten times smaller for some traits. There was thus a problem of "missing heritability" and different hypotheses were proposed to help find this "missing heritability". These hypotheses involved novel research strategies in which different groups engaged including among others increasing sample sizes of GWAS or looking for rare variants and structural variations that were not captured by the SNP-chips used in GWAS. How successful have these efforts been in finding the "missing heritability"? Could it be that the problem of "missing heritability" was ill-defined? These are the questions that will be addressed in this paper by taking some different examples of complex traits.
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Registered trials
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