ArticleCell metabolism2020
Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.
Article in Cell metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Genome-wide association study provides novel insight into the genetic architecture of severe obesity.PLoS genetics · 2025Pooled it
- The bi-directional association between bipolar disorder and obesity: Evidence from Meta and bioinformatics analysis.International journal of obesity (2005) · 2023Pooled it
- IMPROVE 2025: The 3rd International Meeting on Pathway-Related Obesity: Vision & Evidence.Clinical obesity · 2026Article
- Integrated Genomic and Transcriptomic Analysis Reveals the Genetic Basis and Causal Association Between Obesity and Atrial Fibrillation.Diabetes, obesity & metabolism · 2026Article
- Chung-Jansen Syndrome in a Young Woman with a PHIP Variant: Severe Obesity, Intellectual Disability, and Endocrine Abnormalities.Journal of clinical medicine · 2026Article
- Hypothalamic obesity.Reviews in endocrine & metabolic disorders · 2026Review
- Systematic common and rare variant association testing in 392,030 whole genomes inmedRxiv : the preprint server for health sciences · 2026Article
- The genetics of obesity: aetiology, prevention and therapy.Nature metabolism · 2026Review
- The Signal in the Extreme: A Systematic Outlier Framework Identifies Discrete Immunometabolic Subtypes in Human and Cellular Models.Medical sciences (Basel, Switzerland) · 2026Article
- Sleep-Disordered Breathing in Chung-Jansen Syndrome.International journal of molecular sciences · 2026Article
- Modeling genotype-by-environment interactions across climatic conditions reveals environment-specific genomic regions and candidate genes underlying feed efficiency traits in tropical beef cattle.Scientific reports · 2026Article
- Novel Insights: A Novel PHIP Variant in a Family with Severe Early-Onset Obesity.Hormone research in paediatrics · 2026Article
- Cross-species studies implicate the melanocortin 3 receptor more strongly in the control of pubertal development than energy balance.Molecular metabolism · 2026Article
- Severe obesity as an oligogenic condition: evidence from 1714 adults seeking treatment in the UK National Health Service.Human genomics · 2025Article
- The landscape of germline variants in breast and colorectal cancer susceptibility genes in patients with pituitary tumours.Journal of neuro-oncology · 2025Article
- Neuroendocrinology and the Genetics of Obesity.Endocrinology · 2025Review
- Multi-phase, multi-ethnic GWAS uncovers putative loci in predisposition to elite sprint and power performance, health and disease.Biology of sport · 2025Article
- Genetic etiology and clinical features of non-syndromic pediatric obesity in the Chinese population: a large cohort study.BMC pediatrics · 2025Article
- The Interplay of UCP3 and PCSK1 Variants in Severe Obesity.Current obesity reports · 2025Review
- Towards a genetic obesity risk score in a single-center study of children and adolescents with obesity.Scientific reports · 2025Article
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22 authors at 7 institutions in 4 countries.
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Abstract
Obesity is genetically heterogeneous with monogenic and complex polygenic forms. Using exome and targeted sequencing in 2,737 severely obese cases and 6,704 controls, we identified three genes (PHIP, DGKI, and ZMYM4) with an excess burden of very rare predicted deleterious variants in cases. In cells, we found that nuclear PHIP (pleckstrin homology domain interacting protein) directly enhances transcription of pro-opiomelanocortin (POMC), a neuropeptide that suppresses appetite. Obesity-associated PHIP variants repressed POMC transcription. Our demonstration that PHIP is involved in human energy homeostasis through transcriptional regulation of central melanocortin signaling has potential diagnostic and therapeutic implications for patients with obesity and developmental delay. Additionally, we found an excess burden of predicted deleterious variants involving genes nearest to loci from obesity genome-wide association studies. Genes and gene sets influencing obesity with variable penetrance provide compelling evidence for a continuum of causality in the genetic architecture of obesity, and explain some of its missing heritability.
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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.