Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
复制标题
DOI：
10.1371/journal.pone.0051954
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Butte NF
中科院分区：
文献类型：
--
作者：
Comuzzie AG;Cole SA;Laston SL;Voruganti VS;Haack K;Gibbs RA;Butte NF
西班牙裔儿童肥胖易感性及其合并症的遗传变异尚未确定。VIVA LA FAMILIA研究旨在从遗传学上绘制西班牙裔人群的儿童肥胖和相关生物学过程。一项全基因组关联研究（GWAS）使用Illumina Infinium技术对815名儿童进行了110万个单核苷酸多态性（SNP）的基因分型。在遗传标记和肥胖相关性状之间进行测量的基因型分析，人体测量、身体组成、生长、代谢物、激素、炎症、饮食、能量消耗、底物利用和身体活动。确定的全基因组重要基因座：1）其他研究中涉及的确证基因（MTNR1B、ZNF 259/APOA 5、XPA/FOXE 1（TTF-2）、DARC、CCR 3、ABO）; 2）在合理的生物学途径中定位的新基因（PCSK 2、ARHGAP 11 A、CHRNA3）; 3）揭示了在肥胖发病机制中具有未知功能的新基因（MATK、COL4A1）。显著的发现包括一个非同义SNP（rs1056513）INADL（p = 1.2E-07）体重; MTNR1B的内含子变异与空腹血糖相关（p = 3.7E-08）;与甘油三酯相关的APOA 5-ZNF 259区域变异（p = 2.5 - 4.8E-08）;与总抗氧化剂相关的PCSK 2内含子变体（p = 7.6E-08）; XPA/FOXE 1中的23个SNP区组（TTF-2）与血清TSH相关（p = 5.5E-08至1.0E-09）;非同义SNP（p = 1.3E-21），内含子SNP（p = 3.6E-13）在DARC中鉴定为MCP-1; ARHGAP 11A中与睡眠持续时间相关的内含子变体（p = 5.0E-08）;以及，在调整体重后，总能量消耗的MATK（p = 2.7E-08）和睡眠能量消耗的CHRNA3（p = 6.0E-08）中的变体。 前所未有的表型分析和高密度SNP基因分型使得能够定位与儿童肥胖病理生理学相关的新遗传位点。
Genetic variants responsible for susceptibility to obesity and its comorbidities among Hispanic children have not been identified. The VIVA LA FAMILIA Study was designed to genetically map childhood obesity and associated biological processes in the Hispanic population. A genome-wide association study (GWAS) entailed genotyping 1.1 million single nucleotide polymorphisms (SNPs) using the Illumina Infinium technology in 815 children. Measured genotype analysis was performed between genetic markers and obesity-related traits i.e., anthropometry, body composition, growth, metabolites, hormones, inflammation, diet, energy expenditure, substrate utilization and physical activity. Identified genome-wide significant loci: 1) corroborated genes implicated in other studies (MTNR1B, ZNF259/APOA5, XPA/FOXE1 (TTF-2), DARC, CCR3, ABO); 2) localized novel genes in plausible biological pathways (PCSK2, ARHGAP11A, CHRNA3); and 3) revealed novel genes with unknown function in obesity pathogenesis (MATK, COL4A1). Salient findings include a nonsynonymous SNP (rs1056513) in INADL (p = 1.2E-07) for weight; an intronic variant in MTNR1B associated with fasting glucose (p = 3.7E-08); variants in the APOA5-ZNF259 region associated with triglycerides (p = 2.5-4.8E-08); an intronic variant in PCSK2 associated with total antioxidants (p = 7.6E-08); a block of 23 SNPs in XPA/FOXE1 (TTF-2) associated with serum TSH (p = 5.5E-08 to 1.0E-09); a nonsynonymous SNP (p = 1.3E-21), an intronic SNP (p = 3.6E-13) in DARC identified for MCP-1; an intronic variant in ARHGAP11A associated with sleep duration (p = 5.0E-08); and, after adjusting for body weight, variants in MATK for total energy expenditure (p = 2.7E-08) and in CHRNA3 for sleeping energy expenditure (p = 6.0E-08). Unprecedented phenotyping and high-density SNP genotyping enabled localization of novel genetic loci associated with the pathophysiology of childhood obesity.
登录
查看更多内容
影响因子：
8
作者：
Barlow, SE;Dietz, WH
通讯作者：
Dietz, WH
影响因子：
7.1
作者：
Butte, Nancy F.;Cai, Guowen;Comuzzie, Anthony G.
通讯作者：
Comuzzie, Anthony G.
影响因子：
30.8
作者：
Bradfield, Jonathan P.;Taal, H. Rob;Timpson, Nicholas J.;Scherag, Andre;Lecoeur, Cecile;Warrington, Nicole M.;Hypponen, Elina;Holst, Claus;Valcarcel, Beatriz;Thiering, Elisabeth;Salem, Rany M.;Schumacher, Fredrick R.;Cousminer, Diana L.;Sleiman, Patrick M. A.;Zhao, Jianhua;Berkowitz, Robert I.;Vimaleswaran, Karani S.;Jarick, Ivonne;Pennell, Craig E.;Evans, David M.;St Pourcain, Beate;Berry, Diane J.;Mook-Kanamori, Dennis O.;Hofman, Albert;Rivadeneira, Fernando;Uitterlinden, Andre G.;van Duijn, Cornelia M.;van der Valk, Ralf J. P.;de Jongste, Johan C.;Postma, Dirkje S.;Boomsma, Dorret I.;Gauderman, W. James;Hassanein, Mohamed T.;Lindgren, Cecilia M.;Magi, Reedik;Boreham, Colin A. G.;Neville, Charlotte E.;Moreno, Luis A.;Elliott, Paul;Pouta, Anneli;Hartikainen, Anna-Liisa;Li, Mingyao;Raitakari, Olli;Lehtimaki, Terho;Eriksson, Johan G.;Palotie, Aarno;Dallongeville, Jean;Das, Shikta;Deloukas, Panos;McMahon, George;Ring, Susan M.;Kemp, John P.;Buxton, Jessica L.;Blakemore, Alexandra I. F.;Bustamante, Mariona;Guxens, Monica;Hirschhorn, Joel N.;Gillman, Matthew W.;Kreiner-Moller, Eskil;Bisgaard, Hans;Gilliland, Frank D.;Heinrich, Joachim;Wheeler, Eleanor;Barroso, Ines;O'Rahilly, Stephen;Meirhaeghe, Aline;Sorensen, Thorkild I. A.;Power, Chris;Palmer, Lyle J.;Hinney, Anke;Widen, Elisabeth;Farooqi, I. Sadaf;McCarthy, Mark I.;Froguel, Philippe;Meyre, David;Hebebrand, Johannes;Jarvelin, Marjo-Riitta;Jaddoe, Vincent W. V.;Smith, George Davey;Hakonarson, Hakon;Grant, Struan F. A.
通讯作者：
Grant, Struan F. A.
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Brautbar, Ariel;Covarrubias, Daniel;Ballantyne, Christie M.
通讯作者：
Ballantyne, Christie M.