SynthesisGenes2020
A Systematic Review of Extreme Phenotype Strategies to Search for Rare Variants in Genetic Studies of Complex Disorders.
Synthesis in Genes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Tools used to appraise the quality of studies included in systematic reviews and meta-analyses in human genetics: a systematic review.European journal of human genetics : EJHG · 2025Pooled it
- Pooled it
- A Systematic Review on the Genetic Contribution to Tinnitus.Journal of the Association for Research in Otolaryngology : JARO · 2024Pooled it
- Systematic Review of Prevalence Studies and Familial Aggregation in Vestibular Migraine.Frontiers in genetics · 2020Pooled it
- Charting the Phenotypic Landscape of FBN1 Variants in Marfan Syndrome With Ectopia Lentis Through Extreme Phenotype Sampling.Investigative ophthalmology & visual science · 2026Article
- Bayesian Genome-Wide Association Study of Feed Efficiency Traits in Pigs.Animals : an open access journal from MDPI · 2026Article
- Wild genes to the rescue: high-throughput genomics reveals the wild source of broomrape resistance in sunflower.Journal of experimental botany · 2026Article
- Genetic Determinants of T-Cell Homeostasis in Critical Illness: An Exploratory Analysis of Immune Gene Variants and TREC Dynamics.Journal of personalized medicine · 2026Article
- Extreme phenotype-derived machine learning reveals susceptibility and resilience signatures for severe diabetic retinopathy.Frontiers in endocrinology · 2026Article
- A Neuron-Like Cellular Model for Severe Tinnitus Associated with Rare Variations in the ANK2 Gene.Molecular neurobiology · 2025Article
- Identifying Rare Germline Variants Associated with Metastatic Prostate Cancer Through an Extreme Phenotype Study.medRxiv : the preprint server for health sciences · 2025Article
- Psychiatric neuroimaging designs for individualised, cohort, and population studies.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Phenotypic spectrum of tinnitus patients bearing rare ANK2 gene variants.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024Article
- Study design features increase replicability in cross-sectional and longitudinal brain-wide association studies.bioRxiv : the preprint server for biology · 2024Article
- A study concept of expeditious clinical enrollment for genetic modifier studies in Charcot-Marie-Tooth neuropathy 1A.Journal of the peripheral nervous system : JPNS · 2024Article
- Weighted burden analysis of rare coding variants in 470,000 exome-sequenced UK Biobank participants characterises effects on hyperlipidaemia risk.Journal of human genetics · 2024Article
- Commentary on "Craniofacial Syndromes and class III phenotype: common genotype fingerprints? A scoping review and meta-analysis".Pediatric research · 2024Article
- Increased burden of rare protein-truncating variants in constrained, brain-specific and synaptic genes in extremely impulsively violent males with antisocial personality disorder.Genes, brain, and behavior · 2024Article
- Identification of Genetic Variants for Diabetic Retinopathy Risk Applying Exome Sequencing in Extreme Phenotypes.BioMed research international · 2024Article
- Need of orthogonal approaches in neurological disease modeling in mouse.Frontiers in molecular neuroscience · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exome sequencing has been commonly used to characterize rare diseases by selecting multiplex families or singletons with an extreme phenotype (EP) and searching for rare variants in coding regions. The EP strategy covers both extreme ends of a disease spectrum and it has been also used to investigate the contribution of rare variants to the heritability of complex clinical traits. We conducted a systematic review to find evidence supporting the use of EP strategies in the search for rare variants in genetic studies of complex diseases and highlight the contribution of rare variations to the genetic structure of polygenic conditions. After assessing the quality of the retrieved records, we selected 19 genetic studies considering EPs to demonstrate genetic association. All studies successfully identified several rare or de novo variants, and many novel candidate genes were also identified by selecting an EP. There is enough evidence to support that the EP approach for patients with an early onset of a disease can contribute to the identification of rare variants in candidate genes or pathways involved in complex diseases. EP patients may contribute to a better understanding of the underlying genetic architecture of common heterogeneous disorders such as tinnitus or age-related hearing loss.
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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 Socratic graph.