Gholami Morteza, Hamidi Armita Kakavand, Naghshband Zeinab, Asadi Mojgan, Amoli Mahsa M
Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
J Diabetes Metab Disord. 2024 Dec 20;24(1):23. doi: 10.1007/s40200-024-01507-2. eCollection 2025 Jun.
This study aims to identify new variants and haplotypes associated with monogenic obesity by analyzing known obesity genes in whole exome sequencing (WES) data.
The monogenic obesity-associated genes were identified by using the National Institutes of Health (NIH) Genetic Testing Registry (GTR) monogenic obesity panels. WES was performed on ( = 49) extremely obese (children under 5 with weight-for-height greater than 3 standard deviations (SD) above the World Health Organization (WHO) Child Growth Standards median) and ( = 50) control nonobese (25 > body mass index (BMI) < 30) subjects without a history of childhood obesity, and also Iranome WES data of healthy subjects ( = 800).
Seventy-four genes were included in WES analyses. After Bonferroni correction, the T allele of rs2275155 on was significantly associated with the increased risk of obesity for allelic and co-dominant models (˂0.05). Also, a significant association was observed for the T allele of rs116167439 on and the T allele of rs201676524 a rare variant on ; for allelic, dominant, overdominant, and co-dominant models (˂0.05). In the haplotype association study, TC on ), CATA (on ), CAA, CTA, CAAA, and TTGA (on ) haplotypes showed significant associations with monogenic obesity ( < 0.05).
This study suggested that the T allele of two common variants rs2275155 and rs116167439, also rare variant rs201676524 are associated with an increased risk of monogenic obesity. The significant haplotype associations indicate these variants may be in linkage with causative rare variants and should be considered in future studies.
The online version contains supplementary material available at 10.1007/s40200-024-01507-2.
本研究旨在通过分析全外显子组测序（WES）数据中的已知肥胖基因，鉴定与单基因肥胖相关的新变异和单倍型。
利用美国国立卫生研究院（NIH）遗传检测注册库（GTR）的单基因肥胖检测板鉴定与单基因肥胖相关的基因。对49名极度肥胖者（5岁以下身高体重比高于世界卫生组织（WHO）儿童生长标准中位数3个标准差（SD）的儿童）和50名对照非肥胖者（体重指数（BMI）在25至30之间）且无儿童肥胖病史的受试者进行WES检测，同时对800名健康受试者的伊朗外显子组WES数据进行分析。
WES分析纳入了74个基因。经过Bonferroni校正后，14号染色体上rs2275155的T等位基因在等位基因模型和共显性模型中与肥胖风险增加显著相关（P<0.05）。此外，7号染色体上rs116167439的T等位基因和14号染色体上一个罕见变异rs201676524的T等位基因在等位基因、显性、超显性和共显性模型中也观察到显著关联（P<0.05）。在单倍型关联研究中，14号染色体上的TC、7号染色体上的CATA、14号染色体上的CAA、CTA、CAAA和TTGA单倍型与单基因肥胖显著相关（P<0.05）。
本研究表明，两个常见变异rs2275155和rs116167439的T等位基因以及罕见变异rs201676524与单基因肥胖风险增加相关。显著的单倍型关联表明这些变异可能与致病性罕见变异连锁，应在未来研究中予以考虑。
在线版本包含可在10.1007/s40200-024-01507-2获取的补充材料。
