1. Vitamin D and cause-specific vascular disease and mortality: a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults
- Author
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Huang, Tao, Afzal, Shoaib, Yu, Canqing, Guo, Yu, Bian, Zheng, Yang, Ling, Millwood, Iona Y., Walters, Robin G., Chen, Yiping, Chen, Ningyu, Gao, Ruqin, Chen, Junshi, Clarke, Robert, Chen, Zhengming, Ellervik, Christina, Nordestgaard, Børge G., Lv, Jun, Li, Liming, Collins, Rory, Peto, Richard, Avery, Daniel, Boxall, Ruth, Bennett, Derrick, Chang, Yumei, Du, Huaidong, Gilbert, Simon, Hacker, Alex, Hill, Mike, Holmes, Michael, Iona, Andri, Kartsonaki, Christiana, Kerosi, Rene, Kong, Ling, Kurmi, Om, Lancaster, Garry, Lewington, Sarah, Lin, Kuang, McDonnell, John, 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, Xiaoming, Han, Xiao, Hou, Can, Pei, Pei, Liu, Chao, Tan, Yunlong, Pang, Zengchang, Li, Shanpeng, Wang, Shaojie, Liu, Yongmei, Du, Ranran, Zang, Yajing, Cheng, Liang, Tian, Xiaocao, Zhang, Hua, Zhai, Yaoming, Ning, Feng, Sun, Xiaohui, Li, Feifei, Lv, Silu, Wang, Junzheng, Hou, Wei, Zeng, Mingyuan, Jiang, Ge, Zhou, Xue, Yang, Liqiu, He, Hui, Yu, Bo, Li, Yanjie, Xu, Qinai, Kang, Quan, Guo, Ziyan, Wang, Dan, Hu, Ximin, Chen, Jinyan, Fu, Yan, Fu, Zhenwang, Wang, Xiaohuan, Weng, Min, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, Fu, Zhifang, Wu, Ming, Zhou, Yonglin, Zhou, Jinyi, Tao, Ran, Yang, Jie, Su, Jian, Liu, Fang, 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, Lan, Jian, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Wang, Ping, Meng, Fanwen, Qin, Yulu, Wang, Sisi, Wu, Xianping, Zhang, Ningmei, Zhou, Weiwei, Luo, Guojin, Li, Jianguo, Chen, Xiaofang, 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, Hu, Chen, Zhang, Xukui, Wu, Huifang, He, Pan, Yu, Min, Hu, Ruying, Wang, Hao, Qian, Yijian, Wang, Chunmei, Xie, Kaixu, Chen, Lingli, Zhang, Yidan, Pan, Dongxia, Gu, Qijun, Huang, Yuelong, Chen, Biyun, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Qiaohua, Xu, Xin, Zhang, Hao, Long, Huajun, Li, Xianzhi, Zhang, Libo, and Qiu, Zhe
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Adult ,medicine.medical_specialty ,lcsh:Medicine ,Disease ,Lower risk ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Causal effect ,Vitamin D and neurology ,Humans ,Medicine ,Vascular Diseases ,030212 general & internal medicine ,Myocardial infarction ,Vitamin D ,Mendelian randomisation ,Stroke ,business.industry ,Vascular disease ,Confounding ,lcsh:R ,General Medicine ,Vitamin D Deficiency ,medicine.disease ,Lipids ,3. Good health ,Cardiovascular diseases ,Population study ,Gene-Environment Interaction ,business ,030217 neurology & neurosurgery ,Research Article - Abstract
Background Randomised control trials and genetic analyses have demonstrated that vitamin D or 25-hydroxyvitamin D (25[OH]D) levels may not play a causal role in the development of cardiovascular disease. However, it is unclear if 25(OH)D is causally associated with cause-specific vascular disease and lipids. Therefore, we examined the causal association of 25(OH)D with myocardial infarction, stroke, ischaemic heart disease, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and lipid levels among both Chinese and Europeans. Methods We used a Mendelian randomisation (MR) design in the China Kadoorie Biobank, the Copenhagen City Heart Study, and the Copenhagen General Population Study. The 25(OH)D-related genetic variants in the CYP2R1 and DCHR7 genes were genotyped in 99,012 Chinese adults and 106,911 Danish adults. Results In Chinese adults, plasma 25(OH)D levels were not significantly associated with cause-specific vascular disease or mortality, with the exception of intracerebral haemorrhage (HR, 1.09 [95% CI, 1.01,1.18] per 25 nmol/L higher plasma 25(OH)D). In Europeans, plasma 25(OH)D levels were inversely associated with all types of vascular diseases and mortality. However, MR analysis did not demonstrate causal associations of genetically increased 25(OH)D levels with cause-specific vascular diseases, or mortality in both Chinese and European adults. In addition, each 25 nmol/L higher 25(OH)D was observationally associated with lower total cholesterol and low-density lipoprotein cholesterol levels, but higher high-density lipoprotein cholesterol levels. Likewise, MR analysis showed that 25(OH)D levels were not causally associated with lipids in both Chinese and European adults after Bonferroni correction. Conclusions We found no evidence to support that genetically increased 25(OH)D was associated with a lower risk of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and lipid levels in both Chinese and European adults. These results suggest that the inverse associations of vitamin D with vascular disease could be the result of confounding. Electronic supplementary material The online version of this article (10.1186/s12916-019-1401-y) contains supplementary material, which is available to authorized users.
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- 2019