Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Clin Chem. 2020 Dec 1;66(12):1548-1557. doi: 10.1093/clinchem/hvaa227.
Adiponectin is a protein hormone produced by adipocytes that may play an important role in obesity. However, the causal interrelation between plasma adiponectin and body mass index (BMI) is still uncertain. We tested the hypotheses that (a) plasma adiponectin and BMI are inversely associated observationally, (b) genetically high BMI is associated with lower plasma adiponectin, and (c) genetically high plasma adiponectin is associated with lower BMI.
Information on 108 896 individuals from the Copenhagen General Population Study was used in observational and bidirectional one-sample Mendelian randomization analyses, using 5 genetic variants for BMI and 3 for adiponectin. For independent confirmation, information on 322 154 individuals from the GIANT consortium, and 29 347 individuals from the ADIPOGen consortium was used in bidirectional two-sample Mendelian randomization analysis, using 68 genetic variants for BMI and 14 for adiponectin.
In observational analyses, a 1 kg/m2 increase in BMI was associated with -0.44 µg/mL (95% confidence interval: -0.46, -0.42) in plasma adiponectin, whereas a 1 µg/mL increase in plasma adiponectin was associated with -0.11 kg/m2 (-0.12, -0.11) in BMI. In causal genetic analyses, no associations were observed between BMI and plasma adiponectin and vice versa. In one-sample Mendelian randomization analyses, a 1 kg/m2 genetically determined increase in BMI was associated with -0.13 µg/mL (-0.53, 0.28) in plasma adiponectin, whereas a 1 µg/mL genetically determined increase in plasma adiponectin was associated with 0.01 kg/m2 (-0.05, 0.07) in BMI. Corresponding estimates in the two-sample Mendelian randomization analyses were 0.03 µg/mL (-0.02, 0.07) and 0.03 kg/m2(-0.02, 0.07), respectively.
Observationally, plasma adiponectin and BMI are inversely associated. In contrast, genetically high plasma adiponectin is unlikely to influence BMI, and genetically high BMI is unlikely to influence plasma adiponectin.
脂联素是一种由脂肪细胞产生的蛋白激素，它可能在肥胖中起着重要作用。然而，血浆脂联素与体重指数（BMI）之间的因果关系仍不确定。我们检验了以下假设：（a）血浆脂联素和 BMI 呈负相关；（b）遗传上较高的 BMI 与较低的血浆脂联素有关；（c）遗传上较高的血浆脂联素与较低的 BMI 有关。
使用来自哥本哈根普通人群研究的 108896 名个体的信息，进行观察性和单向样本 Mendelian 随机化分析，使用 5 个 BMI 遗传变异和 3 个脂联素遗传变异。为了进行独立验证，使用 GIANT 联盟的 322154 名个体和 ADIPOGen 联盟的 29347 名个体的信息，进行双向两样本 Mendelian 随机化分析，使用 68 个 BMI 遗传变异和 14 个脂联素遗传变异。
在观察性分析中，BMI 每增加 1kg/m2，血浆脂联素降低 -0.44µg/mL（95%置信区间：-0.46，-0.42），而血浆脂联素每增加 1µg/mL，BMI 降低 -0.11kg/m2（-0.12，-0.11）。在因果遗传分析中，未观察到 BMI 和血浆脂联素之间存在关联，反之亦然。在单样本 Mendelian 随机化分析中，遗传上 BMI 每增加 1kg/m2，血浆脂联素降低 -0.13µg/mL（-0.53，0.28），而遗传上血浆脂联素每增加 1µg/mL，BMI 增加 0.01kg/m2（-0.05，0.07）。在两样本 Mendelian 随机化分析中，相应的估计值分别为 0.03µg/mL（-0.02，0.07）和 0.03kg/m2（-0.02，0.07）。
观察性研究表明，血浆脂联素和 BMI 呈负相关。相反，遗传上较高的血浆脂联素不太可能影响 BMI，而遗传上较高的 BMI 也不太可能影响血浆脂联素。
