Obesity research & clinical practice · 2026
Genetic burden of rare leptin-melanocortin variants in pediatric nonsyndromic obesity: Evidence from a Taiwanese cohort.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Chang Yu-Ming, Hwang Daw-Yang, Chou Yen-Yin, Pan Yu-Wen, Weng Yun-Han, Tsai Meng-Che
Аннотация
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.
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.