Association of genetic Loci with glucose levels in childhood and adolescence: a meta-analysis of over 6,000 children.
Association of genetic Loci with glucose levels in childhood and adolescence: a meta-analysis of over 6,000 children.
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DOI：
10.2337/db10-1575
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发表时间：
2011-06
期刊：
影响因子：
7.7
通讯作者：
Langenberg C
中科院分区：
文献类型：
--
作者：
Barker A;Sharp SJ;Timpson NJ;Bouatia-Naji N;Warrington NM;Kanoni S;Beilin LJ;Brage S;Deloukas P;Evans DM;Grontved A;Hassanali N;Lawlor DA;Lecoeur C;Loos RJ;Lye SJ;McCarthy MI;Mori TA;Ndiaye NC;Newnham JP;Ntalla I;Pennell CE;St Pourcain B;Prokopenko I;Ring SM;Sattar N;Visvikis-Siest S;Dedoussis GV;Palmer LJ;Froguel P;Smith GD;Ekelund U;Wareham NJ;Langenberg C
探究在非糖尿病成年人中近期发现的与空腹血糖或胰岛素水平相关的常见基因变异在健康儿童和青少年中是否可检测到。
在六项针对欧洲血统儿童和青少年的研究中，对总共16个与空腹血糖相关的单核苷酸多态性（SNP）进行了基因分型，这些研究包括6000多名9 - 16岁的男孩和女孩。我们进行了荟萃分析，以检验单个SNP以及16个基因座的加权风险评分与空腹血糖的关联。
9个基因座与健康儿童和青少年的血糖水平相关，其中4种关联在先前的研究中已有报道，5种在此首次报道（GLIS3、PROX1、SLC2A2、ADCY5和CRY2）。效应量与成年人相似，表明这些空腹血糖基因座的作用与年龄无关。携带G6PC2、MTNR1B、GCK和GLIS3升糖等位基因的儿童和青少年，根据β细胞功能的稳态模型评估，其β细胞功能也有所降低。使用加权风险评分进行的分析显示，评分每增加一个单位，空腹血糖水平升高[β（95%置信区间）]0.026 mmol/L（0.021 - 0.031）。
在成年人全基因组关联研究中发现的新的空腹血糖基因座与健康儿童和青少年空腹血糖水平的改变相关，且效应量与成年人相当。在非糖尿病成年人中，空腹血糖随时间变化很小，我们的研究结果表明，空腹血糖基因座的作用与年龄无关，这导致了从儿童期开始个体间血糖水平的长期差异。
To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9–16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced β-cell function, as indicated by homeostasis model assessment of β-cell function. Analysis using a weighted risk score showed an increase [β (95% CI)] in fasting glucose level of 0.026 mmol/L (0.021–0.031) for each unit increase in the score. Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
8.2
作者：
Lee, Joyce M.
通讯作者：
Lee, Joyce M.
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：
30.8
作者：
Prokopenko I;Langenberg C;Florez JC;Saxena R;Soranzo N;Thorleifsson G;Loos RJ;Manning AK;Jackson AU;Aulchenko Y;Potter SC;Erdos MR;Sanna S;Hottenga JJ;Wheeler E;Kaakinen M;Lyssenko V;Chen WM;Ahmadi K;Beckmann JS;Bergman RN;Bochud M;Bonnycastle LL;Buchanan TA;Cao A;Cervino A;Coin L;Collins FS;Crisponi L;de Geus EJ;Dehghan A;Deloukas P;Doney AS;Elliott P;Freimer N;Gateva V;Herder C;Hofman A;Hughes TE;Hunt S;Illig T;Inouye M;Isomaa B;Johnson T;Kong A;Krestyaninova M;Kuusisto J;Laakso M;Lim N;Lindblad U;Lindgren CM;McCann OT;Mohlke KL;Morris AD;Naitza S;Orrù M;Palmer CN;Pouta A;Randall J;Rathmann W;Saramies J;Scheet P;Scott LJ;Scuteri A;Sharp S;Sijbrands E;Smit JH;Song K;Steinthorsdottir V;Stringham HM;Tuomi T;Tuomilehto J;Uitterlinden AG;Voight BF;Waterworth D;Wichmann HE;Willemsen G;Witteman JC;Yuan X;Zhao JH;Zeggini E;Schlessinger D;Sandhu M;Boomsma DI;Uda M;Spector TD;Penninx BW;Altshuler D;Vollenweider P;Jarvelin MR;Lakatta E;Waeber G;Fox CS;Peltonen L;Groop LC;Mooser V;Cupples LA;Thorsteinsdottir U;Boehnke M;Barroso I;Van Duijn C;Dupuis J;Watanabe RM;Stefansson K;McCarthy MI;Wareham NJ;Meigs JB;Abecasis GR
通讯作者：
Abecasis GR
影响因子：
30.8
作者：
Bouatia-Naji, Nabila;Bonnefond, Amelie;Froguel, Philippe
通讯作者：
Froguel, Philippe