Effects of general and central adiposity on circulating lipoprotein, lipid, and metabolite levels in UK Biobank: A multivariable Mendelian randomization study.
Effects of general and central adiposity on circulating lipoprotein, lipid, and metabolite levels in UK Biobank: A multivariable Mendelian randomization study.
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DOI：
10.1016/j.lanepe.2022.100457
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发表时间：
2022-10
影响因子：
20.9
通讯作者：
Smith, George Davey
中科院分区：
文献类型：
--
作者：
Bell, Joshua A.;Richardson, Tom G.;Wang, Qin;Sanderson, Eleanor;Palmer, Tom;Walker, Venexia;O'Keeffe, Linda M.;Timpson, Nicholas J.;Cichonska, Anna;Julkunen, Heli;Wurtz, Peter;V. Holmes, Michael;Smith, George Davey
全身性肥胖（体重指数（BMI））和中心性肥胖（腰臀比（WHR））对循环脂蛋白、脂质和代谢物的直接影响尚不清楚。我们使用了来自英国生物银行的新代谢数据（N= 109，532，比以前的研究高5倍）。EDTA-血浆被用来量化249性状与核磁共振光谱，包括亚类特异性脂蛋白浓度和脂质含量，加上前血糖和炎症代谢产物。我们使用单变量和多变量两阶段最小二乘回归模型，以BMI和WHR的遗传风险评分为工具，估计BMI和WHR对代谢特征的总（未校正）和直接（相互校正）影响;加上对他汀类药物使用的影响以及性别，他汀类药物使用和年龄（药物使用的代理）的相互作用。在WHR调整前后，较高的BMI降低了载脂蛋白B和低密度脂蛋白胆固醇（LDL-C），而BMI仅在WHR调整前增加了甘油三酯。腰臀比的这些影响更大，且与BMI无关。直接影响因性别而明显不同，例如，男性甘油三酯仅随BMI增加而增加，女性甘油三酯仅随WHR增加而增加。肥胖测量增加了他汀类药物的使用，并显示出不同的他汀类药物使用和年龄的代谢影响。在最年轻的人群中（38- 53岁，他汀类药物-5%），BMI和WHR（每标准差）增加LDL-C（总效应：分别为0.04-SD，95%CI=-0.01，0.08和0.10-SD，95%CI= 0.02，0.17），但仅WHR直接增加LDL-C。在年龄最大者（63- 73岁，他汀类药物-29%）中，BMI和WHR直接降低LDL-C（分别为-0.19-SD，95%CI=-0.27，-0.11和-0.05-SD，95%CI=-0.16，0.06）。过度肥胖可能通过集中储存的脂肪增加致动脉粥样硬化脂质和代谢物水平，特别是在女性中。肥胖对降低LDL-C的明显影响可能通过肥胖对他汀类药物使用的影响来解释。英国医学研究理事会;英国心脏基金会;诺和诺德;国家健康研究所;惠康信托基金会;英国癌症研究
The direct effects of general adiposity (body mass index (BMI)) and central adiposity (waist-to-hip-ratio (WHR)) on circulating lipoproteins, lipids, and metabolites are unknown. We used new metabolic data from UK Biobank (N=109,532, a five-fold higher N over previous studies). EDTA-plasma was used to quantify 249 traits with nuclear-magnetic-resonance spectroscopy including subclass-specific lipoprotein concentrations and lipid content, plus pre-glycemic and inflammatory metabolites. We used univariable and multivariable two-stage least-squares regression models with genetic risk scores for BMI and WHR as instruments to estimate total (unadjusted) and direct (mutually-adjusted) effects of BMI and WHR on metabolic traits; plus effects on statin use and interaction by sex, statin use, and age (proxy for medication use). Higher BMI decreased apolipoprotein B and low-density lipoprotein cholesterol (LDL-C) before and after WHR-adjustment, whilst BMI increased triglycerides only before WHR-adjustment. These effects of WHR were larger and BMI-independent. Direct effects differed markedly by sex, e.g., triglycerides increased only with BMI among men, and only with WHR among women. Adiposity measures increased statin use and showed metabolic effects which differed by statin use and age. Among the youngest (38-53y, statins-5%), BMI and WHR (per-SD) increased LDL-C (total effects: 0.04-SD, 95%CI=-0.01,0.08 and 0.10-SD, 95%CI=0.02,0.17 respectively), but only WHR directly. Among the oldest (63-73y, statins-29%), BMI and WHR directly lowered LDL-C (-0.19-SD, 95%CI=-0.27,-0.11 and -0.05-SD, 95%CI=-0.16,0.06 respectively). Excess adiposity likely raises atherogenic lipid and metabolite levels exclusively via adiposity stored centrally, particularly among women. Apparent effects of adiposity on lowering LDL-C are likely explained by an effect of adiposity on statin use. UK Medical Research Council; British Heart Foundation; Novo Nordisk; National Institute for Health Research; Wellcome Trust; Cancer Research UK
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DOI：
10.1136/bmj.g2646
发表时间：
2014-05-14
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Dombrowski SU;Knittle K;Avenell A;Araújo-Soares V;Sniehotta FF
通讯作者：
Sniehotta FF
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
腰围比与心脏代谢性状，2型糖尿病和冠状动脉疾病的遗传关联。
DOI：
10.1001/jama.2016.21042
发表时间：
2017-02-14
期刊：
JAMA
影响因子：
--
作者：
Emdin CA;Khera AV;Natarajan P;Klarin D;Zekavat SM;Hsiao AJ;Kathiresan S
通讯作者：
Kathiresan S
肥胖，代谢产物和大肠癌风险：孟德尔随机研究。
影响因子：
9.3
作者：
Bull CJ;Bell JA;Murphy N;Sanderson E;Davey Smith G;Timpson NJ;Banbury BL;Albanes D;Berndt SI;Bézieau S;Bishop DT;Brenner H;Buchanan DD;Burnett-Hartman A;Casey G;Castellví-Bel S;Chan AT;Chang-Claude J;Cross AJ;de la Chapelle A;Figueiredo JC;Gallinger SJ;Gapstur SM;Giles GG;Gruber SB;Gsur A;Hampe J;Hampel H;Harrison TA;Hoffmeister M;Hsu L;Huang WY;Huyghe JR;Jenkins MA;Joshu CE;Keku TO;Kühn T;Kweon SS;Le Marchand L;Li CI;Li L;Lindblom A;Martín V;May AM;Milne RL;Moreno V;Newcomb PA;Offit K;Ogino S;Phipps AI;Platz EA;Potter JD;Qu C;Quirós JR;Rennert G;Riboli E;Sakoda LC;Schafmayer C;Schoen RE;Slattery ML;Tangen CM;Tsilidis KK;Ulrich CM;van Duijnhoven FJB;van Guelpen B;Visvanathan K;Vodicka P;Vodickova L;Wang H;White E;Wolk A;Woods MO;Wu AH;Campbell PT;Zheng W;Peters U;Vincent EE;Gunter MJ
通讯作者：
Gunter MJ
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S