当前位置: X-MOL 学术Nat. Genet. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Effect of sequence variants on variance in glucose levels predicts type 2 diabetes risk and accounts for heritability.
Nature Genetics ( IF 30.8 ) Pub Date : 2017-Sep-01 , DOI: 10.1038/ng.3928
Erna V Ivarsdottir , Valgerdur Steinthorsdottir , Maryam S Daneshpour , Gudmar Thorleifsson , Patrick Sulem , Hilma Holm , Snaevar Sigurdsson , Astradur B Hreidarsson , Gunnar Sigurdsson , Ragnar Bjarnason , Arni V Thorsson , Rafn Benediktsson , Gudmundur Eyjolfsson , Olof Sigurdardottir , Isleifur Olafsson , Sirous Zeinali , Fereidoun Azizi , Unnur Thorsteinsdottir , Daniel F Gudbjartsson , Kari Stefansson

Sequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.7% per allele, P = 4.2 × 10-10), whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance (7.5% per allele, P = 4.9 × 10-11 and 7.3% per allele, P = 7.5 × 10-18, respectively). Variants that increase mean and between-subject variance in fasting glucose levels tend to increase T2D risk, whereas those that increase the mean but reduce variance do not (r2 = 0.61). The variants that increase between-subject variance increase fasting glucose heritability estimates. Intuitively, our results show that increasing the mean and variance of glucose levels is more likely to cause pathologically high glucose levels than increase in the mean offset by a decrease in variance.

中文翻译:

序列变异对葡萄糖水平变异的影响预测了2型糖尿病的风险并解释了遗传性。

影响平均空腹血糖水平的序列变体不一定影响2型糖尿病(T2D)的风险。我们评估了69,142例冰岛人中36种报道的葡萄糖相关序列变异对空腹血糖水平受试者间差异的影响。TCF7L2中增加空腹血糖水平的变异增加受试者间变异(每个等位基因5.7%,P = 4.2×10 -10),而GCK和G6PC2中升高空腹血糖水平的变异减少受试者间变异(每个等位基因7.5%) ,P = 4.9×10 -11和每个等位基因的7.3%,P = 7.5×10 -18, 分别)。在空腹血糖水平上增加均值和受试者间差异的变异往往会增加T2D风险,而那些增加均值却降低差异的变异却没有(r 2 = 0.61)。个体间差异增加的变异体会增加空腹血糖的遗传估计值。直观地,我们的结果表明,增加血糖水平的均值和方差比引起方差减少的均值偏移增加更可能导致病理性高血糖水平。
更新日期:2017-08-31
down
wechat
bug