Genetic Predisposition to Type 2 Diabetes and Risk of Subclinical Atherosclerosis and Cardiovascular Diseases Among 160,000 Chinese Adults
Authors: Gan Wei , Bragg Fiona , Walters Robin G. , Millwood Iona Y. , Lin Kuang , Chen Yiping , Guo Yu , Vaucher Julien , Bian Zheng , Bennett Derrick , Lv Jun , Yu Canqing , Mahajan Anubha , Clarke Robert J. , Li Liming , Holmes Michael V. , McCarthy Mark I. , Chen Zhengming ,   China Kadoorie Biobank Collaborative Group, Chen Junshi , Chen Zhengming , Clarke Robert , Collins Rory , Guo Yu , Li Liming , Lv Jun , Peto Richard , Walters Robin , Avery Daniel , Bennett Derrick , Boxall Ruth , Bragg Fiona , Chang Yumei , Chen Yiping , Du Huaidong , Gilbert Simon , Hacker Alex , Holmes Michael , Iona Andri , Kartsonaki Christiana , Kerosi Rene , Kurmi Om , Lewington Sarah , Lancaster Garry , Lin Kuang , McDonnell John , Millwood Iona , Nie Qunhua , Radhakrishnan Jayakrishnan , Ryder Paul , Sansome Sam , Schmidt Dan , Sherliker Paul , Sohoni Rajani , Stevens Becky , Turnbull Iain , Wang Jenny , Wang Lin , Wright Neil , Yang Ling , Yang Xiaoming , Bian Zheng , Chen Ge , Han Xiao , Hou Can , Pei Pei , Qu Shuzhen , Tan Yunlong , Yu Canqing , Pang Zengchang , Gao Ruqin , Wang Shaojie , Liu Yongmei , Du Ranran , Zang Yajing , Cheng Liang , Tian Xiaocao , Zhang Hua , Lv Silu , Wang Junzheng , Hou Wei , Yin Jiyuan , Jiang Ge , Zhou Xue , Yang Liqiu , He Hui , Yu Bo , Li Yanjie , Mu Huaiyi , Xu Qinai , Dou Meiling , Ren Jiaojiao , Wang Shanqing , Hu Ximin , Wang Hongmei , Chen Jinyan , Fu Yan , Fu Zhenwang , Wang Xiaohuan , Weng Min , Zheng Xiangyang , Li Yilei , Li Huimei , Wang Yanjun , Wu Ming , Zhou Jinyi , Tao Ran , Yang Jie , Ni Chuanming , Zhang Jun , Hu Yihe , Lu Yan , Ma Liangcai , Tang Aiyu , Zhang Shuo , Jin Jianrong , Liu Jingchao , Tang Zhenzhu , Chen Naying , Huang Ying , Li Mingqiang , Meng Jinhuai , Pan Rong , Jiang Qilian , Zhang Weiyuan , Liu Yun , Wei Liuping , Zhou Liyuan , Chen Ningyu , Guan Hairong , Wu Xianping , Zhang Ningmei , Chen Xiaofang , Tang Xuefeng , Luo Guojin , Li Jianguo , Zhong Xunfu , Liu Jiaqiu , Sun Qiang , Ge Pengfei , Ren Xiaolan , Dong Caixia , Zhang Hui , Mao Enke , Wang Xiaoping , Wang Tao , Zhang Xi , Zhang Ding , Zhou Gang , Feng Shixian , Chang Liang , Fan Lei , Gao Yulian , He Tianyou , Sun Huarong , He Pan , Hu Chen , Lv Qiannan , Zhang Xukui , Yu Min , Hu Ruying , Wang Hao , Qian Yijian , Wang Chunmei , Xie Kaixue , Chen Lingli , Zhang Yidan , Pan Dongxia , Huang Yuelong , Chen Biyun , Yin Li , Jin Donghui , Liu Huilin , Fu Zhongxi , Xu Qiaohua , Xu Xin , Zhang Hao , Xiong Youping , Long Huajun , Li Xianzhi , Zhang Libo , Qiu Zhe 
Published: August 2019

In observational studies, type 2 diabetes is associated with two- to fourfold higher risk of cardiovascular diseases (CVD). Using data from the China Kadoorie Biobank (CKB), we examined associations of genetically predicted type 2 diabetes with CVD among ∼160,000 participants to assess whether these relationships are causal. A type 2 diabetes genetic risk score (comprising 48 established risk variants) was associated with the presence of carotid plaque (odds ratio 1.17 [95% CI 1.05, 1.29] per 1 unit higher log-odds of type 2 diabetes; n = 6,819) and elevated risk of ischemic stroke (IS) (1.08 [1.02, 1.14]; n = 17,097), nonlacunar IS (1.09 [1.03, 1.16]; n = 13,924), and major coronary event (1.12 [1.02, 1.23]; n = 5,081). There was no significant association with lacunar IS (1.03 [0.91, 1.16], n = 3,173) or intracerebral hemorrhage (ICH) (1.01 [0.94, 1.10], n = 6,973), although effect estimates were imprecise. These associations were consistent with observational associations of type 2 diabetes with CVD in CKB (P for heterogeneity &gt;0.3) and with the associations of type 2 diabetes with IS, ICH, and coronary heart disease in two-sample Mendelian randomization analyses based on summary statistics from European population genome-wide association studies (P for heterogeneity &gt;0.2). In conclusion, among Chinese adults, genetic predisposition to type 2 diabetes was associated with atherosclerotic CVD, consistent with a causal association.