Genome-wide association of pericardial fat identifies a unique locus for ectopic fat.
Genome-wide association of pericardial fat identifies a unique locus for ectopic fat.
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DOI：
10.1371/journal.pgen.1002705
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Fox CS;White CC;Lohman K;Heard-Costa N;Cohen P;Zhang Y;Johnson AD;Emilsson V;Liu CT;Chen YD;Taylor KD;Allison M;Budoff M;CARDIoGRAM Consortium;Rotter JI;Carr JJ;Hoffmann U;Ding J;Cupples LA;Liu Y
心包脂肪是一种与冠状动脉钙化和心肌梗死相关的局部脂肪堆积。我们假设遗传基因与心包脂肪有关，独立于其他体脂储存。弗雷明翰心脏研究(FHS)和动脉粥样硬化多种族研究(MESA)对5487名欧洲血统的人的心包脂肪进行了量化。使用标准阵列进行基因分型，并输入∼250万个HapMap SNPs。每项研究都进行了针对年龄、性别、体重和身高进行调整的心包脂肪的全基因组关联分析。进行了加权z-Score荟萃分析，并在MESA研究的另外3602名多民族个体中获得了验证。我们在初级荟萃分析中发现了一个全基因组的显著信号，位于TRIB2附近的rs10198628(MAF0.49，p = 2.7x10-08)。这种单核苷酸多态与内脏脂肪(p = 0.17)或体重指数(p = 0.38)无关，尽管在弗雷明翰心脏研究中，我们观察到内脏脂肪与体重指数(P BMI)调整后的名义意义上的方向性一致(p = 0.01)。我们的发现在MESA研究的非洲血统(n = 1,442，p = 0.001)、西班牙裔(n = 1,399，p = 0.004)和中国人(n = 761，p = 0.007)参与者中表现强劲，综合p值为5.4E-14。我们观察了TRIB2基因在小鼠心包脂肪中的表达。TRIB2附近的rs10198628与心包脂肪有关，但与全身性或内脏肥胖症的测量无关，强化了异位脂肪分布有独特遗传基础的概念。心包脂肪是一种与冠状动脉钙化和心肌梗死相关的局部脂肪堆积。为了测试遗传基因是否与心包脂肪相关，我们测量了5487名欧洲血统个体的心包脂肪。在使用全基因组关联进行无偏筛选后，我们在初级荟萃分析中确定了位于TRIB2附近的rs10198628(MAF0.49，p = 2.7x10-08)的全基因组显著信号。此单核苷酸多态与内脏脂肪(p = 0.17)或体重指数(p = 0.38)无关。我们的发现在MESA研究的多种族参与者中是强有力的，综合p值为5.4E-14。我们观察了TRIB2基因在小鼠心包脂肪中的表达。TRIB2附近的rs10198628与心包脂肪有关，但与全身性或内脏肥胖症的测量无关，强化了异位脂肪分布有独特遗传基础的概念。
Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ∼2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7×10-08). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution. Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. To test whether genetic loci are associated with pericardial fat independent of other body fat depots, we measured pericardial fat in 5,487 individuals of European ancestry. After performing an unbiased screen using genome-wide association, we identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7×10-08). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38). Our findings were robust among multi-ethnic participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution.
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