Effects of adiposity on the human plasma proteome: observational and Mendelian randomisation estimates.
Effects of adiposity on the human plasma proteome: observational and Mendelian randomisation estimates.
复制标题
DOI：
10.1038/s41366-021-00896-1
复制
发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Timpson NJ
中科院分区：
文献类型：
--
作者：
Goudswaard LJ;Bell JA;Hughes DA;Corbin LJ;Walter K;Davey Smith G;Soranzo N;Danesh J;Di Angelantonio E;Ouwehand WH;Watkins NA;Roberts DJ;Butterworth AS;Hers I;Timpson NJ
肥胖的变化与心脏代谢疾病的结果有关，但导致这种疾病暴露的机制尚不清楚。本研究旨在评估体重指数（BMI）对一系列广泛的循环蛋白质的影响。我们使用了来自INTERVAL研究的多达2737名健康参与者的SomaLogic蛋白质组学数据。使用线性回归探索自我报告的BMI与3622种独特血浆蛋白之间的关联。这些都是补充孟德尔随机化（MR）分析使用遗传风险评分（GRS）组成的654 BMI相关的多态性，从最近的全基因组关联研究（GWAS）的成人BMI。使用大卫Bioinformatics 6.8对BMI改变的蛋白质进行疾病富集分析。从观察上看，BMI与1576种蛋白质相关（P < 1.4 × 10−5），尤其是与瘦素和脂肪酸结合蛋白4（FABP 4）呈正相关，与性激素结合球蛋白（SHBG）呈负相关。观察估计值可能混杂，但BMI的GRS与测量的混杂因素无关。MR分析为BMI和包括瘦素在内的八种蛋白质之间的因果关系提供了证据（0.63标准差（SD）/SD BMI，95% CI 0.48-0.79，P = 1.6 × 10−15），FABP 4（0.64 SD/SD BMI，95% CI 0.46-0.83，P = 6.7 × 10−12）和SHBG（−0.45 SD/SD BMI，95% CI −0.65至−0.25，P = 1.4 × 10−5）。观察和MR估计值（R2 = 0.33）的幅度一致，并且有证据表明，BMI改变最强烈的蛋白质富含心血管疾病相关基因。这项研究为肥胖对人类蛋白质组的广泛影响提供了证据。BMI强烈改变的蛋白质包括那些参与调节食欲，性激素和炎症的蛋白质;这些蛋白质也富含心血管疾病相关基因。总之，这些结果有助于将注意力集中在肥胖相关疾病的新蛋白质组特征上。
Variation in adiposity is associated with cardiometabolic disease outcomes, but mechanisms leading from this exposure to disease are unclear. This study aimed to estimate effects of body mass index (BMI) on an extensive set of circulating proteins. We used SomaLogic proteomic data from up to 2737 healthy participants from the INTERVAL study. Associations between self-reported BMI and 3622 unique plasma proteins were explored using linear regression. These were complemented by Mendelian randomisation (MR) analyses using a genetic risk score (GRS) comprised of 654 BMI-associated polymorphisms from a recent genome-wide association study (GWAS) of adult BMI. A disease enrichment analysis was performed using DAVID Bioinformatics 6.8 for proteins which were altered by BMI. Observationally, BMI was associated with 1576 proteins (P < 1.4 × 10−5), with particularly strong evidence for a positive association with leptin and fatty acid-binding protein-4 (FABP4), and a negative association with sex hormone-binding globulin (SHBG). Observational estimates were likely confounded, but the GRS for BMI did not associate with measured confounders. MR analyses provided evidence for a causal relationship between BMI and eight proteins including leptin (0.63 standard deviation (SD) per SD BMI, 95% CI 0.48–0.79, P = 1.6 × 10−15), FABP4 (0.64 SD per SD BMI, 95% CI 0.46–0.83, P = 6.7 × 10−12) and SHBG (−0.45 SD per SD BMI, 95% CI −0.65 to −0.25, P = 1.4 × 10−5). There was agreement in the magnitude of observational and MR estimates (R2 = 0.33) and evidence that proteins most strongly altered by BMI were enriched for genes involved in cardiovascular disease. This study provides evidence for a broad impact of adiposity on the human proteome. Proteins strongly altered by BMI include those involved in regulating appetite, sex hormones and inflammation; such proteins are also enriched for cardiovascular disease-related genes. Altogether, results help focus attention onto new proteomic signatures of obesity-related disease.
登录
查看更多内容
DOI：
10.1016/s0140-6736(17)31928-1
发表时间：
2017-11-25
期刊：
Lancet (London, England)
影响因子：
--
作者：
Di Angelantonio E;Thompson SG;Kaptoge S;Moore C;Walker M;Armitage J;Ouwehand WH;Roberts DJ;Danesh J;INTERVAL Trial Group
通讯作者：
INTERVAL Trial Group
DOI：
10.4137/cmc.s17067
发表时间：
2014
期刊：
Clinical Medicine Insights. Cardiology
影响因子：
--
作者：
Furuhashi M;Saitoh S;Shimamoto K;Miura T
通讯作者：
Miura T
影响因子：
37.8
作者：
Dale CE;Fatemifar G;Palmer TM;White J;Prieto-Merino D;Zabaneh D;Engmann JEL;Shah T;Wong A;Warren HR;McLachlan S;Trompet S;Moldovan M;Morris RW;Sofat R;Kumari M;Hyppönen E;Jefferis BJ;Gaunt TR;Ben-Shlomo Y;Zhou A;Gentry-Maharaj A;Ryan A;UCLEB Consortium; METASTROKE Consortium;Mutsert R;Noordam R;Caulfield MJ;Jukema JW;Worrall BB;Munroe PB;Menon U;Power C;Kuh D;Lawlor DA;Humphries SE;Mook-Kanamori DO;Sattar N;Kivimaki M;Price JF;Davey Smith G;Dudbridge F;Hingorani AD;Holmes MV;Casas JP
通讯作者：
Casas JP
DOI：
10.1111/dom.12124
发表时间：
2014-02
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Garg SK;Maurer H;Reed K;Selagamsetty R
通讯作者：
Selagamsetty R
影响因子：
64.5
作者：
Astle, William J.;Elding, Heather;Soranzo, Nicole
通讯作者：
Soranzo, Nicole