First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes.
First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes.
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DOI：
10.2337/dc18-1032
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发表时间：
2018-11
期刊：
影响因子：
16.2
通讯作者：
Grant SFA
中科院分区：
文献类型：
--
作者：
Cousminer DL;Ahlqvist E;Mishra R;Andersen MK;Chesi A;Hawa MI;Davis A;Hodge KM;Bradfield JP;Zhou K;Guy VC;Åkerlund M;Wod M;Fritsche LG;Vestergaard H;Snyder J;Højlund K;Linneberg A;Käräjämäki A;Brandslund I;Kim CE;Witte D;Sørgjerd EP;Brillon DJ;Pedersen O;Beck-Nielsen H;Grarup N;Pratley RE;Rickels MR;Vella A;Ovalle F;Melander O;Harris RI;Varvel S;Grill VER;Bone Mineral Density in Childhood Study;Hakonarson H;Froguel P;Lonsdale JT;Mauricio D;Schloot NC;Khunti K;Greenbaum CJ;Åsvold BO;Yderstræde KB;Pearson ER;Schwartz S;Voight BF;Hansen T;Tuomi T;Boehm BO;Groop L;Leslie RD;Grant SFA
成人隐匿性自身免疫性糖尿病(LADA)具有1型和2型糖尿病的临床特征；然而，关于LADA的确切定义仍在争论中。了解其遗传基础是深入了解这一糖尿病亚型适当分类的一个潜在策略。我们在欧洲血统的病例受试者和人群控制受试者(n=2,634比5,947)中进行了第一次全基因组关联研究，并与患有1型糖尿病(n=2,454比968)和2型糖尿病(n=2,779比10,396)的病例受试者进行比较。主要的遗传信号主要与1型糖尿病共享，尽管我们观察到全基因组范围内与1型和2型糖尿病都存在正的遗传相关性。此外，我们在已知的1型糖尿病基因座上观察到一个新的独立信号，该信号含有PFKFB3，编码了2型糖尿病中糖酵解和胰岛素信号的调节因子，以及自身免疫性疾病中的炎症和自噬，以及LADA中与关键类型1相关的HLA单倍型频率的减弱，这表明这些是区分儿童期起病的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类型的遗传因素以及更精确的分类策略的必要性。
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 (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 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 PFKFB3, 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.
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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：
30.8
作者：
Onengut-Gumuscu, Suna;Chen, Wei-Min;Burren, Oliver;Cooper, Nick J.;Quinlan, Aaron R.;Mychaleckyj, Josyf C.;Farber, Emily;Bonnie, Jessica K.;Szpak, Michal;Schofield, Ellen;Achuthan, Premanand;Guo, Hui;Fortune, Mary D.;Stevens, Helen;Walker, Neil M.;Ward, Lucas D.;Kundaje, Anshul;Kellis, Manolis;Daly, Mark J.;Barrett, Jeffrey C.;Cooper, Jason D.;Deloukas, Panos;Todd, John A.;Wallace, Chris;Concannon, Patrick;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
DOI：
10.1111/dme.12700
发表时间：
2015-07
期刊：
Diabetic medicine : a journal of the British Diabetic Association
影响因子：
--
作者：
Laugesen E;Østergaard JA;Leslie RD;Danish Diabetes Academy Workshop and Workshop Speakers
通讯作者：
Danish Diabetes Academy Workshop and Workshop Speakers
影响因子：
3.7
作者：
Jia X;Zha T;Wu B;Zhang Y;Chen W;Wang X;Yu H;He G
通讯作者：
He G