PDF(Pubmed)
Abstract：
High cortisol production in Cushing\'s syndrome leads to fat centralisation. The influence of modest cortisol variations on body shape, however, is less clear. We examined potentially causal associations between morning plasma cortisol and body shape and obesity with inverse-variance weighted random-effects models in a two-sample Mendelian randomisation analysis. We used publicly available summary statistics from the CORtisol NETwork (CORNET) consortium, UK Biobank, and the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Only in women, morning plasma cortisol (proxied by ten genetic polymorphisms) was associated positively with waist size reflected in waist-to-hip index (WHI, 0.035 standard deviation (SD) units change per one SD cortisol increase; 95% confidence interval (0.002-0.067); p = 0.036) and \"a body shape index\" (ABSI; 0.039 (0.006-0.071); p = 0.021). There was no evidence for associations with hip index (HI) or body mass index (BMI). Among individual polymorphisms, rs7450600 stood out (chromosome 6; Long Intergenic Non-Protein-Coding RNA 473 gene, LINC00473). Morning plasma cortisol proxied by rs7450600 was associated positively with WHI and inversely with HI and BMI in women and men. Our findings support a causal association of higher morning plasma cortisol with larger waist size in women and highlight LINC00473 as a genetic link between morning plasma cortisol and body shape.
摘要：
库欣综合征中皮质醇的高产生导致脂肪集中。适度的皮质醇变化对身体形状的影响，然而,不太清楚。我们在两个样本孟德尔随机化分析中，使用逆方差加权随机效应模型研究了早晨血浆皮质醇与体形与肥胖之间的潜在因果关系。我们使用了来自Cortisol网络(CORNET)联盟的公开可用的汇总统计数据，英国生物银行,和人体测量性状的遗传研究（GIANT）联盟。只有在女人身上,早晨血浆皮质醇（由10个遗传多态性代表）与腰臀指数（WHI，每增加一个SD皮质醇0.035标准差（SD）单位变化；95％置信区间（0.002-0.067）；p=0.036）和“身体形态指数”（ABSI；0.039（0.006-0.071）；p=0.021）。没有证据表明与髋关节指数（HI）或体重指数（BMI）相关。在个体多态性中，rs7450600脱颖而出（6号染色体；长基因间非蛋白质编码RNA473基因，LINC00473).rs7450600替代的早晨血浆皮质醇与WHI呈正相关，与HI和BMI呈负相关。我们的发现支持女性早晨血浆皮质醇较高与腰围较大之间的因果关系，并强调LINC00473是早晨血浆皮质醇与体形之间的遗传联系。
