目的利用孟德尔随机化方法,探讨免疫细胞与肥胖风险的因果关系。方法从GWAS catalog数据库获取731种免疫细胞与肥胖的数据集,采用逆方差加权法、加权中位数等方法探讨免疫细胞与肥胖的因果关系,并运用Cochran's Q检验、MR-Egger回归...目的利用孟德尔随机化方法,探讨免疫细胞与肥胖风险的因果关系。方法从GWAS catalog数据库获取731种免疫细胞与肥胖的数据集,采用逆方差加权法、加权中位数等方法探讨免疫细胞与肥胖的因果关系,并运用Cochran's Q检验、MR-Egger回归、Leave one out等方法,评价结果的稳定性。结果共发现32种免疫细胞与肥胖存在潜在因果关系(P<0.05),其中经典树突状细胞(cDC,CD80 on CD62L+myeloid DC,P<0.001)与肥胖因果关系最为稳定(P<0.001)。且与肥胖风险呈负向因果关系(OR=0.956,95%CI:0.931~0.982),同时反向孟德尔分析显示肥胖与TBNK细胞(CD45on lymphocyte,P=0.043,OR=1.372,95%CI:1.010~1.865)存在正向因果关系,即CD45 on lymphocyte与肥胖风险互为正向因果关系,经敏感性检验后,正反向结果均具有稳定性。多变量孟德尔分析显示,当32种免疫细胞性状同时激活时,仅TBNK细胞(CD16-CD56 on NK,P=0.016,OR=1.107,95%CI:1.019~1.203)与肥胖存在正向因果关系。结论本研究从遗传学的角度初步揭示免疫细胞与肥胖的因果关系,为未来的精准医学和个体化治疗提供重要的理论基础。展开更多
Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents.Methods A cross-sectional study was conducted including 3,0...Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents.Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity.Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)=0.68;95%confidence interval(CI)=0.59,0.78]and abdominal obesity(OR=0.68;95%CI=0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR=0.31,95%CI=0.19,0.50)or abdominal obesity(OR=0.46,95%CI=0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR=2.06,95%CI=1.09,3.91).Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.展开更多
肥胖是指体重严重超过标准体重范围,其诊断通常会涉及体重指数(body mass index,BMI)的计算。对成年人来说,男性BMI超过27kg/m2,女性BMI超过30kg/m2即为肥胖;对于儿童来说,如果BMI超过95%的同龄人,那么该儿童即被判定患有肥胖症。肥胖...肥胖是指体重严重超过标准体重范围,其诊断通常会涉及体重指数(body mass index,BMI)的计算。对成年人来说,男性BMI超过27kg/m2,女性BMI超过30kg/m2即为肥胖;对于儿童来说,如果BMI超过95%的同龄人,那么该儿童即被判定患有肥胖症。肥胖会让人们更容易患上高血压、糖尿病和抑郁症等疾病,带来终身的健康问题。目前,肥胖影响着全球近7亿成年人;单单在美国,就有380万~540万儿童和青少年患有严重肥胖症[1]。展开更多
文摘目的:非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)存在明显的遗传易感性,脂肪细胞因子通过参与胰岛素抵抗和肝脏脂肪变性等过程,在NAFLD的发生和发展中发挥重要作用,但参与脂肪细胞因子通路的基因与NAFLD之间的关联仍不明确。本研究旨在探索脂肪细胞因子通路的基因多态性位点及其交互作用与肥胖儿童NAFLD的关联。方法:采用病例对照研究,将肥胖儿童分为NAFLD组和对照组。采集受试者外周静脉血2 mL,提取DNA后采用多重PCR和高通量测序对脂肪细胞因子通路的14个单核苷酸多态性(single nucleotide polymorphism,SNP)进行分型检测。采用单因素及多因素Logistic回归分析各SNP与肥胖儿童NAFLD的关联。基于显性模型,联合使用交叉分析和Logistic回归分析相加或相乘交互作用。采用广义多因子降维法(generalized multifactor dimensionality reduction,GMDR)检测14个SNP之间基因-基因交互作用与肥胖儿童NAFLD之间的关联。结果:共纳入1 022例儿童,NAFLD组与对照组各511例。在调整年龄、性别、BMI后,多因素Logistic回归结果显示:PPARG rs1801282在3个遗传模型中与肥胖儿童NAFLD存在关联,分别是杂合子模型(CG vs CC,OR=0.58,95%CI 0.36~0.95,P=0.029)、显性模型(CG+GG vs CC,OR=0.62,95%CI 0.38~1.00,P=0.049)、超显性模型(CC+GG vs CG,OR=1.72,95%CI 1.06~2.80,P=0.028);PRKAG2 rs12703159在4个遗传模型中与肥胖儿童NAFLD存在关联,分别是杂合子模型(CT vs CC,OR=1.51,95%CI 1.10~2.07,P=0.011)、显性模型(CT+TT vs CC,OR=1.50,95%CI 1.10~2.03,P=0.010)、超显性模型(CC+TT vs CT,OR=0.67,95%CI 0.49~0.92,P=0.012)、加性模型(CC vs CT vs TT,OR=1.40,95%CI 1.07~1.83,P=0.015)。但PPARG rs1801282与PRKAG2 rs12703159间的相乘及相加交互作用均与肥胖儿童NAFLD不存在关联。经GMDR分析,调整年龄、性别、BMI后,14个SNP之间的交互作用均无统计学意义(均P>0.05)。结论:PPARG rs1801282、PRKAG2 rs12703159突变型与肥胖儿童NAFLD存在关联,但未发现SNP交互作用与肥胖儿童NAFLD之间的关联。
文摘目的利用孟德尔随机化方法,探讨免疫细胞与肥胖风险的因果关系。方法从GWAS catalog数据库获取731种免疫细胞与肥胖的数据集,采用逆方差加权法、加权中位数等方法探讨免疫细胞与肥胖的因果关系,并运用Cochran's Q检验、MR-Egger回归、Leave one out等方法,评价结果的稳定性。结果共发现32种免疫细胞与肥胖存在潜在因果关系(P<0.05),其中经典树突状细胞(cDC,CD80 on CD62L+myeloid DC,P<0.001)与肥胖因果关系最为稳定(P<0.001)。且与肥胖风险呈负向因果关系(OR=0.956,95%CI:0.931~0.982),同时反向孟德尔分析显示肥胖与TBNK细胞(CD45on lymphocyte,P=0.043,OR=1.372,95%CI:1.010~1.865)存在正向因果关系,即CD45 on lymphocyte与肥胖风险互为正向因果关系,经敏感性检验后,正反向结果均具有稳定性。多变量孟德尔分析显示,当32种免疫细胞性状同时激活时,仅TBNK细胞(CD16-CD56 on NK,P=0.016,OR=1.107,95%CI:1.019~1.203)与肥胖存在正向因果关系。结论本研究从遗传学的角度初步揭示免疫细胞与肥胖的因果关系,为未来的精准医学和个体化治疗提供重要的理论基础。
基金supported by the National Health Commission of the People’s Republic of China Medical Reform Major Program:China National Chronic Diseases and Nutrition Surveillance of Adults[2015-2017]Qianrang Zhu is funded by a China Scholarship Council PhD Scholarship[No.202109110099].
文摘Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents.Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity.Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)=0.68;95%confidence interval(CI)=0.59,0.78]and abdominal obesity(OR=0.68;95%CI=0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR=0.31,95%CI=0.19,0.50)or abdominal obesity(OR=0.46,95%CI=0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR=2.06,95%CI=1.09,3.91).Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.
文摘肥胖是指体重严重超过标准体重范围,其诊断通常会涉及体重指数(body mass index,BMI)的计算。对成年人来说,男性BMI超过27kg/m2,女性BMI超过30kg/m2即为肥胖;对于儿童来说,如果BMI超过95%的同龄人,那么该儿童即被判定患有肥胖症。肥胖会让人们更容易患上高血压、糖尿病和抑郁症等疾病,带来终身的健康问题。目前,肥胖影响着全球近7亿成年人;单单在美国,就有380万~540万儿童和青少年患有严重肥胖症[1]。
