外显子组测序
外显子组
生命银行
肥胖
生物
体质指数
遗传学
基因
疾病
突变
内科学
内分泌学
医学
作者
Lena R Kaisinger,Katherine A. Kentistou,Stasa Stankovic,Eugene J. Gardner,Felix R. Day,Yajie Zhao,Alexander Mörseburg,Christopher J. Carnie,Guido Zagnoli-Vieira,Fabio Puddu,Stephen Jackson,Stephen O’Rahilly,I. Sadaf Farooqi,Laura Dearden,Lucas Carminatti Pantaleão,Susan E. Ozanne,Ken K. Ong,John R. B. Perry
出处
期刊:Cell genomics
[Elsevier]
日期:2023-08-01
卷期号:3 (8): 100362-100362
被引量:4
标识
DOI:10.1016/j.xgen.2023.100362
摘要
Obesity contributes substantially to the global burden of disease and has a significant heritable component. Recent large-scale exome sequencing studies identified several genes in which rare, protein-coding variants have large effects on adult body mass index (BMI). Here we extended such work by performing sex-stratified associations in the UK Biobank study (N∼420,000). We identified genes in which rare heterozygous loss-of-function increases adult BMI in women (DIDO1, PTPRG, and SLC12A5) and in men (SLTM), with effect sizes up to ∼8 kg/m2. This is complemented by analyses implicating rare variants in OBSCN and MADD for recalled childhood adiposity. The known functions of these genes, as well as findings of common variant genome-wide pathway enrichment analyses, suggest a role for neuron death, apoptosis, and DNA damage response mechanisms in the susceptibility to obesity across the life-course. These findings highlight the importance of considering sex-specific and life-course effects in the genetic regulation of obesity.
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