Causal Relevance of Lp(a) for Coronary Heart Disease and Stroke Types in East Asian and European Ancestry Populations: A Mendelian Randomization Study

作者：Robert Clarke, Neil Wright, Kuang Lin, Canqing Yu, Robin Walters, Jun Lv, Michael Hill, Christiana Kartsonaki, Iona Y. Millwood, Derrick Bennett, Daniel Avery, Ling Yang, Yiping Chen, Huaidong Du, Paul Sherliker, Xiaoming Yang, Dianjianyi Sun, Liming Li, Chan Qu, Santica M. Marcovina, Rory Collins, Zhengming Chen, Sarah Parish, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Maxim Barnard, Derrick Bennett, Ruth Boxall, Ka Hung Chan, Yiping Chen, Zhengming Chen, Charlotte Clarke, Jonathan Clarke, Robert Clarke, Huaidong Du, Ahmed Edris Mohamed, Hannah Fry, Simon Gilbert, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Kshitij Kolhe, Hubert Lam, Kuang Lin, James Liu, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozarickij, Maryam Rahmati, Paul Ryder, Dan Schmidt, Becky Stevens, Iain Turnbull, Robin Walters, Baihan Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Pang Yao, Xiao Han, Can Hou, Qingmei Xia, Chao Liu, Jun Lv, Pei Pei, Dianjianyi Sun, Canqing Yu, Lang Pan, Zengchang Pang, Ruqin Gao, Shanpeng Li, Haiping Duan, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li, Silu Lv, Junzheng Wang, Wei Hou, Wei Sun, Shichun Yan, Xiaoming Cui, Chi Wang, Zhenyuan Wu, Yanjie Li, Quan Kang, Huiming Luo, Tingting Ou, Xiangyang Zheng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su, Fang Liu, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Mei Lin, Zhenzhen Lu, Lifang Zhou, Changping Xie, Jian Lan, Tingping Zhu, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Yulu Qin, Sisi Wang, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xiaoyu Chang, Mingqiang Yuan, Xia Wu, Xiaofang Chen, Wei Jiang, Jiaqiu Liu, Qiang Sun, Faqing Chen, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi zhang, Kai Kang, Shixian Feng, Huizi Tian, Lei Fan, XiaoLin Li, Huarong Sun, Pan He, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Xiaoyi Zhang, Yuan Cao, Kaixu Xie, Lingli Chen, Dun Shen, Xiaojun Li, Donghui Jin, Li Yin, Huilin Liu, Zhongxi Fu, Xin Xu, Hao Zhang, Jianwei Chen, Yuan Peng, Libo Zhang, Chan Qu · 发表于：Circulation · 年份：2025 · DOI：10.1161/circulationaha.124.072086 · 被引用次数：19 · 研究领域：Lipoproteins and Cardiovascular Health、Atherosclerosis and Cardiovascular Diseases、Diabetes, Cardiovascular Risks, and Lipoproteins

BACKGROUND: Elevated plasma levels of Lp(a) [lipoprotein(a)] are a causal risk factor for coronary heart disease and stroke in European individuals, but the causal relevance of Lp(a) for different stroke types and in East Asian individuals with different Lp(a) genetic architecture is uncertain. METHODS: We measured plasma levels of Lp(a) in a nested case-control study of 18 174 adults (mean [SD] age, 57 [10] years; 49% female) in the China Kadoorie Biobank (CKB) and performed a genome-wide association analysis to identify genetic variants affecting Lp(a) levels, with replication in ancestry-specific subsets in UK Biobank. We further performed 2-sample Mendelian randomization analyses, associating ancestry-specific Lp(a)-associated instrumental variants derived from CKB or from published data in European individuals with risk of myocardial infarction (n=17 091), ischemic stroke (IS [n=29 233]) and its subtypes, or intracerebral hemorrhage (n=5845) in East Asian and European individuals using available data from CKB and genome-wide association analysis consortia. RESULTS: In CKB observational analyses, plasma levels of Lp(a) were log-linearly and positively associated with higher risks of myocardial infarction and IS, but not with intracerebral hemorrhage. In genome-wide association analysis, we identified 29 single nucleotide polymorphisms independently associated with Lp(a) that together explained 33% of variance in Lp(a) in Chinese individuals. In UK Biobank, the lead Chines...