Association between adiposity and facial aging: results from a Mendelian randomization study.
Association between adiposity and facial aging: results from a Mendelian randomization study.
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DOI：
10.1186/s40001-023-01236-x
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发表时间：
2023-09-15
影响因子：
4.2
通讯作者：
Feng, Jingwei
中科院分区：
文献类型：
--
作者：
Liu, Meiqi;Feng, Jingwei
皮肤作为一个具有社会学意义的界面，具有不同于其他器官的心理学意义，特别是在全球人口老龄化的背景下。越来越多的证据表明，面部衰老与肥胖风险增加有关。然而，现有的研究是观察性的，虽然他们可能会发现一些相关性，但很难简单地解开非因果或反向因果联系，因为这些联系可能会混淆或无法准确反映真正的因果联系。我们进行了一项双样本孟德尔随机（MR）研究，以检查面部衰老对广泛肥胖风险及其三个主要肥胖指标（包括体重指数（BMI），体脂百分比（BF%）和腰围（WC））的潜在影响。来自IEU OpenGWAS项目的遗传仪器，这是最大的面部衰老全基因组关联研究（GWAS）之一（423，999个样本），用于调查与广泛肥胖的关系（32，858例，65，839对照）。采用逆方差加权（IVW）技术，研究了与肥胖指标（BMI（461，460个样本）、BF%（454，633个样本）和WC（462，166个样本））相关的单核苷酸多态性（SNPs）与面部衰老的关系。进行了进一步的敏感性分析，包括孟德尔随机化-Egger（MR-Egger）、加权中位数估计和留一分析，以评价MR研究中结果的一致性和相关的潜在问题。我们在17个广泛的肥胖相关SNPs中发现了肥胖和面部衰老之间强而显著的相关性。（IVW估计比值比OR = 1.020，95% CI 1.010-1.029，P = 7.303e-05），458个BMI相关SNP（IVW估计比值比OR = 1.047，95%CI 1.0357-1.058，P = 1.154e-16），对于395个BF%相关SNP（OR = 1.056，95%CI 1.040- 1.072，P = 7.617e − 12），或374个WC相关SNP（OR = 1.072，95%CI 1057- 1.087，P = 1.229e − 23）。一系列的补充方法已被用来评估水平多效性和相关的潜在警告发生在MR研究。使用孟德尔随机化作为调查因果关系的另一种方法，我们发现肥胖和面部衰老之间存在因果关系，这在统计学上是强有力的。在线版本包含补充材料，可通过10.1186/s40001-023-01236-x获得。使用双样本孟德尔随机化，我们发现肥胖（及其三个主要肥胖指标，包括体重指数，体脂百分比和腰围）与面部衰老之间存在因果关系，这在统计学上是强有力的。在三个肥胖指标中，WC与面部老化有更好的因果关系，这表明皮下脂肪可能比内脏脂肪在面部老化中具有更大的贡献。随后的多变量MR分析（面部衰老的三个主要肥胖指标）和内脏/皮下脂肪组织与面部衰老之间的两个样本MR分析的阴性结果显示了更详细的因果关系。在线版本包含补充材料，可通过10.1186/s40001-023-01236-x获得。
Skin, as a sociologically meaningful interface, has psychological implications different from other organs, particularly in the context of the global population aging. Growing evidence suggests that facial aging is associated with an increased risk of adiposity. Existing research, however, were observational, and while they may find some correlations, it is difficult to simply disentangle non-causal or reverse-causal links because these associations may be confounded or fail to accurately reflect true causative linkages. We conducted a 2-sample Mendelian randomization (MR) study to examine the potential effect of facial aging on the risk of broad obesity and its three major adiposity indicators, including body mass index (BMI), body fat percentage (BF%) and waist circumference (WC). Genetic instruments from IEU OpenGWAS project, one of the largest available genome-wide association studies (GWAS) for facial aging (423,999 samples) were used to investigate the relation to broad obesity (32,858 cases, 65,839 controls). Using the inverse-variance weighted (IVW) technique, single nucleotide polymorphisms (SNPs) associated with adiposity indicators (BMI (461,460 samples), BF% (454,633 samples), and WC (462,166 samples)) were investigated in relationship to facial aging. Further sensitivity analyses were performed, including Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, to evaluate the consistency of the results and related potential issues in MR studies. We identified strong and significant correlations between adiposity and facial aging in the 17 broad obesity-associated SNPs (IVW estimate of odds ratio OR = 1.020, 95% CI 1.010–1.029, P = 7.303e − 05), 458 BMI-associated SNPs (IVW estimate of odds ratio OR = 1.047, 95% CI 1.0357–1.058, P = 1.154e − 16),for the 395 BF%-associated SNPs (OR = 1.056, 95%CI 1.040–1.072,P = 7.617e − 12), or for the 374 WC-associated SNPs (OR = 1.072, 95% CI 1057–1.087,P = 1.229e − 23). A range of complementary methodologies have been employed to evaluate horizontal pleiotropy and related potential caveats occurring in MR research. Using Mendelian randomization as an alternative approach to investigate causality, we found a causal relationship between adiposity and facial aging, which was statistically strong and significant. The online version contains supplementary material available at 10.1186/s40001-023-01236-x. Using a two-sample Mendelian randomization, we found a causal relationship between adiposity (and its three major adiposity indicators, including body mass index, body fat percentage and waist circumference) and facial aging, which was statistically strong and significant. Among the three adiposity indicators, WC had a better casual association with facial aging, which indicated that subcutaneous fat may present a major contribution in facial aging compared with visceral fat. More detailed causal relationship was revealed in negative results of subsequent multivariable MR analysis (three major adiposity indicators with facial aging) and two sample MR analysis between visceral/subcutaneous adipose tissue and facial aging. The online version contains supplementary material available at 10.1186/s40001-023-01236-x.
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影响因子：
12.3
作者：
Lyon MS;Andrews SJ;Elsworth B;Gaunt TR;Hemani G;Marcora E
通讯作者：
Marcora E
影响因子：
64.8
作者：
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Perry JRB
影响因子：
2.1
作者：
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影响因子：
7.4
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影响因子：
13.8
作者：
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