Genome-wide association study for the interaction between BMR and BMI in obese Korean women including overweight.

Genome-wide association study for the interaction between BMR and BMI in obese Korean women including overweight.
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DOI:
10.4162/nrp.2016.10.1.115
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发表时间:
2016-02
影响因子:
2.4
通讯作者:
Kim AJ
Kim AJ
中科院分区:
医学4区
文献类型:
--
作者:
Lee M;Kwon DY;Kim MS;Choi CR;Park MY;Kim AJ

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这是第一项研究,以确定共同的遗传因素与基础代谢率(BMR)和身体质量指数(BMI)的肥胖韩国妇女,包括超重。为进一步研究肥胖基因与BMR的相互作用奠定了基础。实验设计为2 × 2,变量为BMR和BMI。在超重和肥胖(BMI > 23 kg/m2)与正常人相比,以及在低BMR(< 1426.3 kcal/d)与高BMR相比的女性中进行单核苷酸多态性(SNP)的全基因组关联研究(GWAS)。在本研究中,共有140个SNPs达到正式的全基因组统计学显著性(P < 1 × 10-4)。调查,估计能量摄入量,使用24小时回忆法为三天,问卷调查的家族史,体检,体育活动进行。我们发现10q23.1染色体区域的两个NRG 3基因SNPs与BMR(rs 10786764; P = 8.0 × 10-7,rs 1040675; 2.3 × 10-6)和BMI(rs 10786764; P = 2.5 × 10-5,rs 10786764; 6.57 × 10-5)高度相关。其他与BMI相关的基因(HSD 52、TMA 16、MARCH 1、NRG 1、NRXN 3和STK 4)产生P <10 × 10-4。在韩国肥胖妇女中发现5个与BMR和BMI相关的新基因座,包括NRG 3、OR 8 U8、BCL 2L 2-PABPN 1、PABPN 1和SLC 22 A17(P < 1 × 10-4)。在问卷调查中,发现各组在每周饥饿次数、胃癌家族史、咖啡摄入量和体重控制试验方面存在显著差异。我们使用GWAS发现了几个常见的BMR和BMI相关基因。虽然这些新建立的基因座中的大多数以前与肥胖无关,但它们可能为体重调节提供新的见解。我们在韩国人中发现的与BMR和BMI相关的五个常见基因将作为复制和验证未来代谢率研究的参考。
This is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction. The experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > 23 kg/m2) compared to the normality, and in women with low BMR (< 1426.3 kcal/day) compared to high BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P < 1 × 10-4). Surveys to estimate energy intake using 24-h recall method for three days and questionnaires for family history, a medical examination, and physical activities were conducted. We found that two NRG3 gene SNPs in the 10q23.1 chromosomal region were highly associated with BMR (rs10786764; P = 8.0 × 10-7, rs1040675; 2.3 × 10-6) and BMI (rs10786764; P = 2.5 × 10-5, rs10786764; 6.57 × 10-5). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P <10 × 10-4. Five new loci associated with BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P < 1 × 10-4). In the questionnaire investigation, significant differences were found in the number of starvation periods per week, family history of stomach cancer, coffee intake, and trial of weight control in each group. We discovered several common BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate.