ArticleGenome biology and evolution2016
Atopic Dermatitis Susceptibility Variants in Filaggrin Hitchhike Hornerin Selective Sweep.
Article in Genome biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Evolutionary Balancing of Genetic Consequence and Innovation in Mammals Through Variable Number Tandem Repeats.Genome biology and evolution · 2026Review
- HaploSweep: Detecting and Distinguishing Recent Soft and Hard Selective Sweeps through Haplotype Structure.Molecular biology and evolution · 2024Article
- Rare Filaggrin Variants Are Associated with Pustular Skin Diseases in Asians.International journal of molecular sciences · 2024Article
- Inborn Errors of Immunity Predisposing to Herpes Simplex Virus Infections of the Central Nervous System.Pathogens (Basel, Switzerland) · 2023Review
- Genetic Variants in Epidermal Differentiation Complex Genes as Predictive Biomarkers for Atopic Eczema, Allergic Sensitization, and Eczema-Associated Asthma in a 6-Year Follow-Up Case-Control Study in Children.Journal of clinical medicine · 2022Article
- The evolution of human skin pigmentation involved the interactions of genetic, environmental, and cultural variables.Pigment cell & melanoma research · 2021Review
- FLG Variation Differs between European Americans and African Americans.The Journal of investigative dermatology · 2021Observational
- Selective sweep for an enhancer involucrin allele identifies skin barrier adaptation out of Africa.Nature communications · 2021Article
- Evolutionary context of psoriatic immune skin response.Evolution, medicine, and public health · 2021Article
- Filaggrin gene mutations with special reference to atopic dermatitis.Current treatment options in allergy · 2020Article
- Associating filaggrin copy number variation and atopic dermatitis in African-Americans: Challenges and opportunities.Journal of dermatological science · 2020Observational
- Filaggrin sequencing and bioinformatics tools.Archives of dermatological research · 2020Article
- An Evolutionary Perspective on the Impact of Genomic Copy Number Variation on Human Health.Journal of molecular evolution · 2020Review
- Genetic ancestry does not explain increased atopic dermatitis susceptibility or worse disease control among African American subjects in 2 large US cohorts.The Journal of allergy and clinical immunology · 2020Article
- Resolving the Insertion Sites of Polymorphic Duplications Reveals a HERC2 Haplotype under Selection.Genome biology and evolution · 2019Article
- Fine-Scale Characterization of Genomic Structural Variation in the Human Genome Reveals Adaptive and Biomedically Relevant Hotspots.Genome biology and evolution · 2019Article
- Tiled array-based sequencing identifies enrichment of loss-of-function variants in the highly homologous filaggrin gene in African-American children with severe atopic dermatitis.Experimental dermatology · 2018Article
- Recent evolution of the human skin barrier.Experimental dermatology · 2018Review
- Archaic Hominin Introgression in Africa Contributes to Functional Salivary MUC7 Genetic Variation.Molecular biology and evolution · 2017Article
- VCFtoTree: a user-friendly tool to construct locus-specific alignments and phylogenies from thousands of anthropologically relevant genome sequences.BMC bioinformatics · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human skin has evolved rapidly, leaving evolutionary signatures in the genome. The filaggrin (FLG) gene is widely studied for its skin-barrier function in humans. The extensive genetic variation in this gene, especially common loss-of-function (LoF) mutations, has been established as primary risk factors for atopic dermatitis. To investigate the evolution of this gene, we analyzed 2,504 human genomes and genotyped the copy number variation of filaggrin repeats within FLG in 126 individuals from diverse ancestral backgrounds. We were unable to replicate a recent study claiming that LoF of FLG is adaptive in northern latitudes with lower ultraviolet light exposure. Instead, we present multiple lines of evidence suggesting that FLG genetic variation, including LoF variants, have little or no effect on fitness in modern humans. Haplotype-level scrutinization of the locus revealed signatures of a recent selective sweep in Asia, which increased the allele frequency of a haplotype group (Huxian haplogroup) in Asian populations. Functionally, we found that the Huxian haplogroup carries dozens of functional variants in FLG and hornerin (HRNR) genes, including those that are associated with atopic dermatitis susceptibility, HRNR expression levels and microbiome diversity on the skin. Our results suggest that the target of the adaptive sweep is HRNR gene function, and the functional FLG variants that involve susceptibility to atopic dermatitis, seem to hitchhike the selective sweep on HRNR. Our study presents a novel case of a locus that harbors clinically relevant common genetic variation with complex evolutionary trajectories.
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