Academic Journal
Genetic burden of rare leptin-melanocortin variants in pediatric nonsyndromic obesity: Evidence from a Taiwanese cohort.
| Τίτλος: | Genetic burden of rare leptin-melanocortin variants in pediatric nonsyndromic obesity: Evidence from a Taiwanese cohort. |
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| Συγγραφείς: | Chang YM; Department of Genomic Medicine, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan; Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan., Hwang DY; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan., Chou YY; Department of Genomic Medicine, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan; Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan., Pan YW; Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan., Weng YH; Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan., Tsai MC; Department of Genomic Medicine, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan; Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan; Department of Medical Humanities and Social Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: mengchets@gs.ncku.edu.tw. |
| Πηγή: | Obesity research & clinical practice [Obes Res Clin Pract] 2026 Sep-Oct; Vol. 20 (5), pp. 401-408. Date of Electronic Publication: 2026 Aug 03. |
| Τύπος έκδοσης: | Journal Article; Observational Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101303911 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1871-403X (Print) Linking ISSN: 1871403X NLM ISO Abbreviation: Obes Res Clin Pract Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier, 2007- |
| Ιατρικοί όροι (MeSH): | Leptin*/genetics , Pediatric Obesity*/genetics, Receptors, Leptin/genetics ; Humans ; Child ; Taiwan ; Female ; Child, Preschool ; Male ; Prospective Studies ; Adolescent ; Genetic Variation ; Genetic Predisposition to Disease |
| Περίληψη: | Background: Rare and deleterious variants in the leptin-melanocortin pathway can underlie severe childhood obesity, but data from East Asian populations remain limited. Methods: We conducted a single-center prospective observational cohort study of 188 Taiwanese children (4-18 years) with nonsyndromic obesity recruited between Jan 2017 and Dec 2024 for targeted sequencing of 12 leptin-melanocortin genes and compared them with two cohorts from the Taiwan Biobank: 527 normal‑weight adults presumed to have normal weight in childhood and 213 obese adults. We compared carrier proportions and mean variant counts and applied the Optimal Sequence Kernel Association Test (SKAT-O) across groups at the pathway and gene levels for three variant sets: all exonic variants, rare variants, and potentially influential variants (PIVs, defined as rare protein-truncating variants or missense variants with high deleteriousness scores). We also analyzed questionnaire-derived eating behavior scores using SKAT-O within the childhood obesity cohort. Results: Children with obesity carried a higher PIV burden than both normal-weight adults (41.0% vs. 24.1%; p < 0.0001) and obese adults (41.0% vs. 25.8%; p = 0.001); mean PIV counts were also higher. Pathway-level SKAT-O supported enrichment driven by rare variants and PIVs. Gene-level enrichment for LEPR and MAGEL2, and variant-level enrichment for two missense variants, MAGEL2 p.Gly285Arg and LEPR p.Asn128Lys, were observed in the childhood obesity group. Analyses of eating‑behavior scores showed nominal signals for exonic variants in MAGEL2 and PIVs in SIM1, but neither met the Bonferroni‑corrected threshold. Conclusions: Rare, putatively deleterious leptin-melanocortin variants, particularly in LEPR and MAGEL2, are enriched in Taiwanese children with nonsyndromic obesity, underscoring the value of pathway-focused genetic evaluation in pediatric obesity. (Copyright © 2026 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Leptin-melanocortin pathway; Pathway analysis; Pediatric obesity; Rare variant |
| Substance Nomenclature: | 0 (Leptin) 0 (Receptors, Leptin) |
| Entry Date(s): | Date Created: 20260803 Date Completed: 20261007 Latest Revision: 20261009 |
| Update Code: | 20261010 |
| DOI: | 10.1016/j.orcp.2026.07.003 |
| PMID: | 42547334 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1871-403X |
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| DOI: | 10.1016/j.orcp.2026.07.003 |