Diabetes Care. 2018 Nov;41(11):2396-2403. doi: 10.2337/dc18-1032. Epub 2018 Sep 25.
Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.
We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects ( = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes ( = 2,454 vs. 968) and type 2 diabetes ( = 2,779 vs. 10,396).
The leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring , encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1-associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes.
Our results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.
成人隐匿性自身免疫性糖尿病（LADA）与 1 型和 2 型糖尿病具有共同的临床特征；然而，关于 LADA 的精确定义仍存在争议。了解其遗传基础是深入了解这种糖尿病亚型适当分类的潜在策略之一。
我们对欧洲血统的 LADA 病例对照（=2634 对 5947）进行了首次全基因组关联研究，并与 1 型糖尿病病例对照（=2454 对 968）和 2 型糖尿病病例对照（=2779 对 10396）进行了比较。
主要的遗传信号与 1 型糖尿病主要相关，但我们在全基因组范围内观察到与 1 型和 2 型糖尿病均存在正遗传相关性。此外，我们在已知的 1 型糖尿病位点上观察到一个新的独立信号，该位点包含编码糖酵解和胰岛素信号通路调节剂的 ，在 2 型糖尿病和自身免疫性疾病中与炎症和自噬有关，以及 LADA 中关键的 1 型相关 HLA 单倍型频率减弱，表明这些是区分儿童期发病的 1 型糖尿病和成人自身免疫性糖尿病的因素。
我们的结果支持进一步研究区分自身免疫性糖尿病形式的遗传因素以及更精确的分类策略的必要性。
