ArticleHuman molecular genetics2015
Homozygous loss-of-function variants in European cosmopolitan and isolate populations.
Article in Human molecular genetics, 2015. 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.
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.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation.The pharmacogenomics journal · 2018Pooled it
- Autism spectrum disorder trios from consanguineous populations are enriched for rare homozygous variants, identifying 32 new candidate genes.Scientific reports · 2026Article
- Search for germline gene variants in colorectal cancer families presenting with multiple primary colorectal cancers.International journal of cancer · 2025Article
- Regionally enriched rare deleterious exonic variants in the UK and Ireland.Nature communications · 2024Article
- Emerging significance of butyrylcholinesterase.World journal of experimental medicine · 2024Review
- The impact of the Turkish population variome on the genomic architecture of rare disease traits.Genetics in medicine open · 2024Article
- The Counteracting Effects of Demography on Functional Genomic Variation: The Roma Paradigm.Molecular biology and evolution · 2021Article
- Less Is More, Natural Loss-of-Function Mutation Is a Strategy for Adaptation.Plant communications · 2020Review
- Comprehensive genome and transcriptome analyses reveal genetic relationship, selection signature, and transcriptome landscape of small-sized Korean native Jeju horse.Scientific reports · 2019Article
- Increased ultra-rare variant load in an isolated Scottish population impacts exonic and regulatory regions.PLoS genetics · 2019Article
- An actionable KCNH2 Long QT Syndrome variant detected by sequence and haplotype analysis in a population research cohort.Scientific reports · 2019Article
- Identifying mouse developmental essential genes using machine learning.Disease models & mechanisms · 2018Article
- Mortality patterns in Southern Adriatic islands of Croatia: a registry-based study.Croatian medical journal · 2018Article
- Runs of homozygosity: windows into population history and trait architecture.Nature reviews. Genetics · 2018Review
- Slightly deleterious genomic variants and transcriptome perturbations in Down syndrome embryonic selection.Genome research · 2018Article
- Natural Knockouts: Natural Selection Knocked Out.Biology · 2017Article
- Settling the score: variant prioritization and Mendelian disease.Nature reviews. Genetics · 2017Review
- The impact of recent population history on the deleterious mutation load in humans and close evolutionary relatives.Current opinion in genetics & development · 2016Review
- Translational plasticity facilitates the accumulation of nonsense genetic variants in the human population.Genome research · 2016Article
- Testing the role of predicted gene knockouts in human anthropometric trait variation.Human molecular genetics · 2016Article
Corrections and comments
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Authors and funding
31 authors at 8 institutions in 4 countries.
Funding
Abstract
Homozygous loss of function (HLOF) variants provide a valuable window on gene function in humans, as well as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown—as are the phenotypic effects of losing function for most human genes. Here, we make use of 1432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, which we show are enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to show that most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation.
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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.