New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
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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。
作者：
循环葡萄糖水平受到严格控制。为了确定新的血糖位点，我们对21项全基因组关联研究进行了荟萃分析，这些研究为多达46，186名非糖尿病参与者的空腹血糖（FG）、空腹胰岛素（FI）和β细胞功能指数（HOMA-B）和胰岛素抵抗（HOMA-IR）提供了信息。对另外76,558名受试者的25个基因座进行随访，发现16个基因座与FG/HOMA-B相关，2个基因座与FI/HOMA-IR相关，其中包括9个新的FG基因座（在ADCY 5、MADD、ADRA 2A、FADS 1、GLIS 3、SLC 2A 2、PROX 1和FAM 148 B中或附近）和1个影响FI/HOMA-IR的基因座（在IGF 1附近）。我们还证明了ADCY 5、PROX 1、GCK、GCKR和DGKB/TMEM 195与2型糖尿病（T2 D）的关联。在这些基因座中，可能的生物学候选基因影响信号转导、细胞增殖、发育、葡萄糖敏感和昼夜节律调节。我们的研究结果表明，血糖性状的遗传研究可以识别T2 D风险位点，以及适度提高FG的位点，但不会导致明显的糖尿病。
Circulating glucose levels are tightly regulated. To identify novel glycemic loci, we performed meta-analyses of 21 genome-wide associations studies informative for fasting glucose (FG), fasting insulin (FI) and indices of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 non-diabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with FG/HOMA-B and two associated with FI/HOMA-IR. These include nine new FG loci (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and FAM148B) and one influencing FI/HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB/TMEM195 with type 2 diabetes (T2D). Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify T2D risk loci, as well as loci that elevate FG modestly, but do not cause overt diabetes.