PDF(Pubmed)
Abstract：
It remains unknown whether adiposity subtypes are differentially associated with colorectal cancer (CRC). To move beyond single-trait anthropometric indicators, we derived four multi-trait body shape phenotypes reflecting adiposity subtypes from principal components analysis on body mass index, height, weight, waist-to-hip ratio, and waist and hip circumference. A generally obese (PC1) and a tall, centrally obese (PC3) body shape were both positively associated with CRC risk in observational analyses in 329,828 UK Biobank participants (3728 cases). In genome-wide association studies in 460,198 UK Biobank participants, we identified 3414 genetic variants across four body shapes and Mendelian randomization analyses confirmed positive associations of PC1 and PC3 with CRC risk (52,775 cases/45,940 controls from GECCO/CORECT/CCFR). Brain tissue-specific genetic instruments, mapped to PC1 through enrichment analysis, were responsible for the relationship between PC1 and CRC, while the relationship between PC3 and CRC was predominantly driven by adipose tissue-specific genetic instruments. This study suggests distinct putative causal pathways between adiposity subtypes and CRC.
摘要：
目前尚不清楚肥胖亚型是否与结直肠癌（CRC）存在差异。为了超越单特征人体测量指标，我们从体重指数的主成分分析中得出了四种反映肥胖亚型的多性状体型表型，高度,体重,腰臀比,腰围和臀围。一般肥胖（PC1）和高个子，在329,828名UKBiobank参与者(3728例)的观察性分析中,中心型肥胖(PC3)的体型均与CRC风险呈正相关.在460,198名英国生物银行参与者的全基因组关联研究中，我们在4种体型中鉴定出3414种遗传变异,孟德尔随机化分析证实PC1和PC3与CRC风险呈正相关(来自GECCO/CORECT/CCFR的52,775例/45,940例对照).脑组织特异性基因仪器,通过富集分析映射到PC1，负责PC1和CRC之间的关系，而PC3和CRC之间的关系主要由脂肪组织特异性遗传工具驱动。这项研究表明肥胖亚型和CRC之间存在明显的因果关系。
