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41 results on '"Fairhurst-Hunter, Zammy"'

1. Causal relevance of different blood pressure traits on risk of cardiovascular diseases: GWAS and Mendelian randomisation in 100,000 Chinese adults

Author

Pozarickij, Alfred, Gan, Wei, Lin, Kuang, Clarke, Robert, Fairhurst-Hunter, Zammy, Koido, Masaru, Kanai, Masahiro, Okada, Yukinori, Kamatani, Yoichiro, Bennett, Derrick, Du, Huaidong, Chen, Yiping, Yang, Ling, Avery, Daniel, Guo, Yu, Yu, Min, Yu, Canqing, Schmidt Valle, Dan, Lv, Jun, Chen, Junshi, Peto, Richard, Collins, Rory, Li, Liming, Chen, Zhengming, Millwood, Iona Y., and Walters, Robin G.

Published
2024
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2. Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease

Author

Zhao, Yajie, Chukanova, Maria, Kentistou, Katherine A., Fairhurst-Hunter, Zammy, Siegert, Anna Maria, Jia, Raina Y., Dowsett, Georgina K. C., Gardner, Eugene J., Lawler, Katherine, Day, Felix R., Kaisinger, Lena R., Tung, Yi-Chun Loraine, Lam, Brian Yee Hong, Chen, Hsiao-Jou Cortina, Wang, Quanli, Berumen-Campos, Jaime, Kuri-Morales, Pablo, Tapia-Conyer, Roberto, Alegre-Diaz, Jesus, Barroso, Inês, Emberson, Jonathan, Torres, Jason M., Collins, Rory, Saleheen, Danish, Smith, Katherine R., Paul, Dirk S., Merkle, Florian, Farooqi, I. Sadaf, Wareham, Nick J., Petrovski, Slavé, O’Rahilly, Stephen, Ong, Ken K., Yeo, Giles S. H., and Perry, John R. B.

Published
2024
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3. A saturated map of common genetic variants associated with human height

Author

Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U, Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D, Graham, Sarah E, Mukamel, Ronen E, Spracklen, Cassandra N, Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H, Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E, Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S, Akiyama, Masato, Allison, Matthew A, Alvarez, Marcus, Andersen, Mette K, Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F, Bollepalli, Sailalitha, Bonnycastle, Lori L, Bork-Jensen, Jette, Bradfield, Jonathan P, Bradford, Yuki, Braund, Peter S, Brody, Jennifer A, Burgdorf, Kristoffer S, Cade, Brian E, Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E Warwick, Degenhard, Frauke, Delgado, Graciela E, Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B, Engmann, Jorgen E, Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D, Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E, Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P, Goel, Anuj, Gordon, Scott D, Gorski, Mathias, Grove, Jakob, and Guo, Xiuqing

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Humans, Body Height, Gene Frequency, Genome, Human, Genome-Wide Association Study, Haplotypes, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Europe, Sample Size, Phenotype, Chromosome Mapping, 23andMe Research Team, VA Million Veteran Program, DiscovEHR, eMERGE, Lifelines Cohort Study, PRACTICAL Consortium, Understanding Society Scientific Group, General Science & Technology
Abstract

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

Published
2022

4. Causal association between snoring and stroke: a Mendelian randomization study in a Chinese population

Author

Chen, Junshi, Chen, Zhengming, Clarke, Robert, Collins, Rory, Guo, Yu, Li, Liming, Lv, Jun, Peto, Richard, Walter, Robin, Avery, Daniel, Bennett, Derrick, Boxall, Ruth, Burgess, Sue, Chan, Ka Hung, Chang, Yumei, Chen, Yiping, Clarke, Johnathan, Du, Huaidong, Mohamed, Ahmed Edris, Fairhurst-Hunter, Zammy, Fry, Hannah, Hill, Mike, Holmes, Michael, Im, Pek Kei, Iona, Andri, Kakkoura, Maria, Kartsonaki, Christiana, Kerosi, Rene, Lin, Kuang, Mazidi, Mohsen, Millwood, Iona, Morris, Sam, Nie, Qunhua, Pozarickij, Alfred, Ryder, Paul, Said, Saredo, Schmidt, Dan, Sherliker, Paul, Stevens, Becky, Turnbull, Iain, Walters, Robin, Wang, Lin, Wright, Neil, Yang, Ling, Yang, Xiaoming, Yao, Pang, Han, Xiao, Hou, Can, Pei, Pei, Liu, Chao, Yu, Canqing, Xia, Qingmei, Pang, Zengchang, Gao, Ruqin, Li, Shanpeng, Duan, Haiping, 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, Sun, Wei, Yan, Shichun, Cui, Xiaoming, Wang, Chi, Wu, Zhenyuan, Li, Yanjie, Kang, Quan, Luo, Huiming, Ou, Tingting, Zheng, Xiangyang, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, 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, Lin, Mei, Lu, Zhenzhen, Zhou, Lifang, Xie, Changping, Lan, Jian, Zhu, Tingping, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Chen, Ningyu, Qin, Yulu, Wang, Sisi, Wu, Xianping, Zhang, Ningmei, Chen, Xiaofang, Chang, Xiaoyu, Yuan, Mingqiang, Wu, Xia, Jiang, Wei, Liu, Jiaqiu, Sun, Qiang, Chen, Faqing, Ren, Xiaolan, Dong, Caixia, Zhang, Hui, Mao, Enke, Wang, Xiaoping, Wang, Tao, zhang, Xi, Kang, Kai, Feng, Shixian, Tian, Huizi, Fan, Lei, Li, XiaoLin, Sun, Huarong, He, Pan, Zhang, Xukui, Yu, Min, Hu, Ruying, Wang, Hao, Zhang, Xiaoyi, Cao, Yuan, Xie, Kaixu, Chen, Lingli, Shen, Dun, Li, Xiaojun, Jin, Donghui, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Xin, Zhang, Hao, Chen, Jianwei, Peng, Yuan, Zhang, Libo, Qu, Chan, Zhu, Yunqing, Zhuang, Zhenhuang, Sun, Dianjianyi, Millwood, Iona Y., and Walters, Robin G.

Published
2024
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7. A wide landscape of morbidity and mortality risk associated with marital status in 0.5 million Chinese men and women: a prospective cohort study

Author

Chen, Junshi, Chen (PI, Zhengming, Clarke, Robert, Collins, Rory, Guo, Yu, Li (PI, Liming, Lv, Jun, Peto, Richard, Walters, Robin, Avery, Daniel, Bennett, Derrick, Boxall, Ruth, Burgess, Sue, Chan, Ka Hung, Chang, Yumei, Chen, Yiping, Chen, Zhengming, Clarke, Johnathan, Du, Huaidong, Mohamed, Ahmed Edris, Fairhurst-Hunter, Zammy, Fry, Hannah, Hill, Mike, Holmes, Michael, Im, Pek Kei, Iona, Andri, Kakkoura, Maria, Kartsonaki, Christiana, Kerosi, Rene, Lin, Kuang, Mazidi, Mohsen, Millwood, Iona, Morris, Sam, Nie, Qunhua, Pozarickij, Alfred, Ryder, Paul, Said, Saredo, Schmidt, Dan, Sherliker, Paul, Stevens, Becky, Turnbull, Iain, Wang, Lin, Wright, Neil, Yang, Ling, Yang, Xiaoming, Yao, Pang, Han, Xiao, Hou, Can, Pei, Pei, Liu, Chao, Yu, Canqing, Xia, Qingmei, Pang, Zengchang, Gao, Ruqin, Li, Shanpeng, Duan, Haiping, 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, Sun, Wei, Yan, Shichun, Cui, Xiaoming, Wang, Chi, Wu, Zhenyuan, Li, Yanjie, Kang, Quan, Luo, Huiming, Ou, Tingting, Zheng, Xiangyang, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, 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, Lin, Mei, Lu, Zhenzhen, Zhou, Lifang, Xie, Changping, Lan, Jian, Zhu, Tingping, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Chen, Ningyu, Qin, Yulu, Wang, Sisi, Wu, Xianping, Zhang, Ningmei, Chen, Xiaofang, Chang, Xiaoyu, Yuan, Mingqiang, Wu, Xia, Jiang, Wei, Liu, Jiaqiu, Sun, Qiang, Chen, Faqing, Ren, Xiaolan, Dong, Caixia, Zhang, Hui, Mao, Enke, Wang, Xiaoping, Wang, Tao, zhang, Xi, Kang, Kai, Feng, Shixian, Tian, Huizi, Fan, Lei, Li, XiaoLin, Sun, Huarong, He, Pan, Zhang, Xukui, Yu, Min, Hu, Ruying, Wang, Hao, Zhang, Xiaoyi, Cao, Yuan, Xie, Kaixu, Chen, Lingli, Shen, Dun, Li, Xiaojun, Jin, Donghui, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Xin, Zhang, Hao, Chen, Jianwei, Peng, Yuan, Zhang, Libo, Qu, Chan, Xiao, Meng, Li, Aolin, Wang, Yueqing, Pang, Yuanjie, Li, Liming, and Sun, Dianjianyi

Published
2024
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8. Long-Term Exposure to Fine Particulate Matter and Incidence of Esophageal Cancer: A Prospective Study of 0.5 Million Chinese Adults

Author

Chen, Junshi, Chen, Zhengming, Clarke, Robert, Collins, Rory, Guo, Yu, Li, Liming, Peto, Richard, Walters, Robin, Avery, Daniel, Bennett, Derrick, Boxall, Ruth, Burgess, Sue, Chan, Ka Hung, Chang, Yumei, Chen, Yiping, Clarke, Johnathan, Du, Huaidong, Mohamed, Ahmed Edris, Fairhurst-Hunter, Zammy, Fry, Hannah, Gilbert, Simon, Hacker, Alex, Hill, Mike, Holmes, Michael, Im, Pek Kei, Iona, Andri, Kakkoura, Maria, Kartsonaki, Christiana, Kerosi, Rene, Lin, Kuang, Mazidi, Mohsen, Millwood, Iona, Morris, Sam, Nie, Qunhua, Pozarickij, Alfred, Ryder, Paul, Said, Saredo, Sansome, Sam, Schmidt, Dan, Sherliker, Paul, Sohoni, Rajani, Stevens, Becky, Turnbull, Iain, Wang, Lin, Wright, Neil, Yang, Ling, Yang, Xiaoming, Yao, Pang, Han, Xiao, Hou, Can, Lv, Jun, Pei, Pei, Liu, Chao, Yu, Canqing, Xia, Qingmei, Pang, Zengchang, Gao, Ruqin, Li, Shanpeng, Duan, Haiping, 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, Sun, Wei, Yan, Shichun, Cui, Xiaoming, Wang, Chi, Wu, Zhenyuan, Li, Yanjie, Kang, Quan, Luo, Huiming, Ou, Tingting, Zheng, Xiangyang, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, 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, Lin, Mei, Lu, Zhenzhen, Zhou, Lifang, Xie, Changping, Lan, Jian, Zhu, Tingping, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Chen, Ningyu, Qin, Yulu, Wang, Sisi, Wu, Xianping, Zhang, Ningmei, Chen, Xiaofang, Chang, Xiaoyu, Yuan, Mingqiang, Wu, Xia, Jiang, Wei, Liu, Jiaqiu, Sun, Qiang, Chen, Faqing, Ren, Xiaolan, Dong, Caixia, Zhang, Hui, Mao, Enke, Wang, Xiaoping, Wang, Tao, Zhang, Xi, Kang, Kai, Feng, Shixian, Tian, Huizi, Fan, Lei, Li, XiaoLin, Sun, Huarong, He, Pan, Zhang, Xukui, Yu, Min, Hu, Ruying, Wang, Hao, Zhang, Xiaoyi, Cao, Yuan, Xie, Kaixu, Chen, Lingli, Shen, Dun, Li, Xiaojun, Jin, Donghui, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Xin, Zhang, Hao, Chen, Jianwei, Peng, Yuan, Zhang, Libo, Qu, Chan, Sun, Dong, Liu, Cong, Zhu, Yunqing, Sun, Dianjianyi, Pang, Yuanjie, Meng, Xia, Liu, Yang, and Kan, Haidong

Published
2023
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11. Conventional and genetic associations of BMI with major vascular and non-vascular disease incidence and mortality in a relatively lean Chinese population: U-shaped relationship revisited.

Author

Iona, Andri, Bragg, Fiona, Fairhurst-Hunter, Zammy, Millwood, Iona Y, Wright, Neil, Lin, Kuang, Yang, Ling, Du, Huaidong, Chen, Yiping, Pei, Pei, Cheng, Liang, Schmidt, Dan, Avery, Daniel, Yu, Canqing, Lv, Jun, Clarke, Robert, Walters, Robin, Li, Liming, Parish, Sarah, and Chen, Zhengming

Subjects
BODY mass index, CEREBRAL hemorrhage, ISCHEMIC stroke, CHINESE people, STROKE
Abstract

Background Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels. Methods The prospective China Kadoorie Biobank recruited >512 000 adults aged 30–79 years in 2004–08 and genotyped a random subset of 76 000 participants. In conventional and Mendelian randomization (MR) analyses, Cox regression yielded adjusted hazard ratios (HRs) associating measured and genetically predicted BMI levels with incident risks of major vascular events (MVEs; conventional/MR 68 431/23 621), ischaemic heart disease (IHD; 50 698/12 177), ischaemic stroke (IS; 42 427/11 897) and intracerebral haemorrhage (ICH; 7644/4712), and with mortality risks of CVD (15 427/6781), non-CVD (26 915/4355) and all causes (42 342/6784), recorded during ∼12 years of follow-up. Results Overall, the mean BMI was 23.8 (standard deviation: 3.2) kg/m2 and 13% had BMIs of <20 kg/m2. Measured and genetically predicted BMI showed positive log-linear associations with MVE, IHD and IS, but a shallower positive association with ICH in conventional analyses. Adjusted HRs per 5 kg/m2 higher genetically predicted BMI were 1.50 (95% CI 1.41–1.58), 1.49 (1.38–1.61), 1.42 (1.31–1.54) and 1.64 (1.58–1.69) for MVE, IHD, IS and ICH, respectively. These were stronger than associations in conventional analyses [1.21 (1.20–1.23), 1.28 (1.26–1.29), 1.31 (1.29–1.33) and 1.14 (1.10–1.18), respectively]. At BMIs of ≥20 kg/m2, there were stronger positive log-linear associations of BMI with CVD, non-CVD and all-cause mortality in MR than in conventional analyses. Conclusions Among relatively lean Chinese adults, higher genetically predicted BMI was associated with higher risks of incident CVDs. Excess mortality risks at lower BMI in conventional analyses are likely not causal and may reflect residual reverse causality. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Causal association between snoring and stroke: a Mendelian randomization study in a Chinese population

Author

Zhu, Yunqing, primary, Zhuang, Zhenhuang, additional, Lv, Jun, additional, Sun, Dianjianyi, additional, Pei, Pei, additional, Yang, Ling, additional, Millwood, Iona Y., additional, Walters, Robin G., additional, Chen, Yiping, additional, Du, Huaidong, additional, Wu, Xianping, additional, Schmidt, Dan, additional, Avery, Daniel, additional, Chen, Junshi, additional, Chen, Zhengming, additional, Li, Liming, additional, Yu, Canqing, additional, Clarke, Robert, additional, Collins, Rory, additional, Guo, Yu, additional, Peto, Richard, additional, Walter, Robin, additional, Bennett, Derrick, additional, Boxall, Ruth, additional, Burgess, Sue, additional, Chan, Ka Hung, additional, Chang, Yumei, additional, Clarke, Johnathan, additional, Mohamed, Ahmed Edris, additional, Fairhurst-Hunter, Zammy, additional, Fry, Hannah, additional, Hill, Mike, additional, Holmes, Michael, additional, Im, Pek Kei, additional, Iona, Andri, additional, Kakkoura, Maria, additional, Kartsonaki, Christiana, additional, Kerosi, Rene, additional, Lin, Kuang, additional, Mazidi, Mohsen, additional, Millwood, Iona, additional, Morris, Sam, additional, Nie, Qunhua, additional, Pozarickij, Alfred, additional, Ryder, Paul, additional, Said, Saredo, additional, Sherliker, Paul, additional, Stevens, Becky, additional, Turnbull, Iain, additional, Walters, Robin, additional, Wang, Lin, additional, Wright, Neil, additional, Yang, Xiaoming, additional, Yao, Pang, additional, Han, Xiao, additional, Hou, Can, additional, Liu, Chao, additional, Xia, Qingmei, additional, Pang, Zengchang, additional, Gao, Ruqin, additional, Li, Shanpeng, additional, Duan, Haiping, additional, Wang, Shaojie, additional, Liu, Yongmei, additional, Du, Ranran, additional, Zang, Yajing, additional, Cheng, Liang, additional, Tian, Xiaocao, additional, Zhang, Hua, additional, Zhai, Yaoming, additional, Ning, Feng, additional, Sun, Xiaohui, additional, Li, Feifei, additional, Lv, Silu, additional, Wang, Junzheng, additional, Hou, Wei, additional, Sun, Wei, additional, Yan, Shichun, additional, Cui, Xiaoming, additional, Wang, Chi, additional, Wu, Zhenyuan, additional, Li, Yanjie, additional, Kang, Quan, additional, Luo, Huiming, additional, Ou, Tingting, additional, Zheng, Xiangyang, additional, Guo, Zhendong, additional, Wu, Shukuan, additional, Li, Yilei, additional, Li, Huimei, additional, Wu, Ming, additional, Zhou, Yonglin, additional, Zhou, Jinyi, additional, Tao, Ran, additional, Yang, Jie, additional, Su, Jian, additional, Liu, Fang, additional, Zhang, Jun, additional, Hu, Yihe, additional, Lu, Yan, additional, Ma, Liangcai, additional, Tang, Aiyu, additional, Zhang, Shuo, additional, Jin, Jianrong, additional, Liu, Jingchao, additional, Lin, Mei, additional, Lu, Zhenzhen, additional, Zhou, Lifang, additional, Xie, Changping, additional, Lan, Jian, additional, Zhu, Tingping, additional, Liu, Yun, additional, Wei, Liuping, additional, Zhou, Liyuan, additional, Chen, Ningyu, additional, Qin, Yulu, additional, Wang, Sisi, additional, Zhang, Ningmei, additional, Chen, Xiaofang, additional, Chang, Xiaoyu, additional, Yuan, Mingqiang, additional, Wu, Xia, additional, Jiang, Wei, additional, Liu, Jiaqiu, additional, Sun, Qiang, additional, Chen, Faqing, additional, Ren, Xiaolan, additional, Dong, Caixia, additional, Zhang, Hui, additional, Mao, Enke, additional, Wang, Xiaoping, additional, Wang, Tao, additional, zhang, Xi, additional, Kang, Kai, additional, Feng, Shixian, additional, Tian, Huizi, additional, Fan, Lei, additional, Li, XiaoLin, additional, Sun, Huarong, additional, He, Pan, additional, Zhang, Xukui, additional, Yu, Min, additional, Hu, Ruying, additional, Wang, Hao, additional, Zhang, Xiaoyi, additional, Cao, Yuan, additional, Xie, Kaixu, additional, Chen, Lingli, additional, Shen, Dun, additional, Li, Xiaojun, additional, Jin, Donghui, additional, Yin, Li, additional, Liu, Huilin, additional, Fu, Zhongxi, additional, Xu, Xin, additional, Zhang, Hao, additional, Chen, Jianwei, additional, Peng, Yuan, additional, Zhang, Libo, additional, and Qu, Chan, additional

Published
2024
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13. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

Author

Schmidt, Amand F, Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S, Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pająk, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E, Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S, McCarty, Catherine A, Kirchner, H Lester, Larson, Eric B, Crosslin, David R, de Andrade, Mariza, Roden, Dan M, Denny, Joshua C, Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M Abdullah, Eppinga, Ruben N, Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O, Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M, Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P, Smith, Daniel J, Meade, Tom, Maitland-van der Zee, Anke H, Baranova, Ekaterina V, Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L, Grobbee, Diederick E, Froguel, Philippe, Thuillier, Dorothée, Balkau, Beverley, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M, Chasman, Daniel I, Reiner, Alex P, Lange, Leslie A, Ritchie, Marylyn D, Asselbergs, Folkert W, Casas, Juan-Pablo, Keating, Brendan J, Preiss, David, Hingorani, Aroon D, and Sattar, Naveed

Published
2017
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14. Long-Term Exposure to Fine Particulate Matter and Incidence of Esophageal Cancer: A Prospective Study of 0.5 Million Chinese Adults

Author

Sun, Dong, primary, Liu, Cong, additional, Zhu, Yunqing, additional, Yu, Canqing, additional, Guo, Yu, additional, Sun, Dianjianyi, additional, Pang, Yuanjie, additional, Pei, Pei, additional, Du, Huaidong, additional, Yang, Ling, additional, Chen, Yiping, additional, Meng, Xia, additional, Liu, Yang, additional, Zhang, Jun, additional, Schmidt, Dan, additional, Avery, Daniel, additional, Chen, Junshi, additional, Chen, Zhengming, additional, Lv, Jun, additional, Kan, Haidong, additional, Li, Liming, additional, Clarke, Robert, additional, Collins, Rory, additional, Peto, Richard, additional, Walters, Robin, additional, Bennett, Derrick, additional, Boxall, Ruth, additional, Burgess, Sue, additional, Chan, Ka Hung, additional, Chang, Yumei, additional, Clarke, Johnathan, additional, Mohamed, Ahmed Edris, additional, Fairhurst-Hunter, Zammy, additional, Fry, Hannah, additional, Gilbert, Simon, additional, Hacker, Alex, additional, Hill, Mike, additional, Holmes, Michael, additional, Im, Pek Kei, additional, Iona, Andri, additional, Kakkoura, Maria, additional, Kartsonaki, Christiana, additional, Kerosi, Rene, additional, Lin, Kuang, additional, Mazidi, Mohsen, additional, Millwood, Iona, additional, Morris, Sam, additional, Nie, Qunhua, additional, Pozarickij, Alfred, additional, Ryder, Paul, additional, Said, Saredo, additional, Sansome, Sam, additional, Sherliker, Paul, additional, Sohoni, Rajani, additional, Stevens, Becky, additional, Turnbull, Iain, additional, Wang, Lin, additional, Wright, Neil, additional, Yang, Xiaoming, additional, Yao, Pang, additional, Han, Xiao, additional, Hou, Can, additional, Liu, Chao, additional, Xia, Qingmei, additional, Pang, Zengchang, additional, Gao, Ruqin, additional, Li, Shanpeng, additional, Duan, Haiping, additional, Wang, Shaojie, additional, Liu, Yongmei, additional, Du, Ranran, additional, Zang, Yajing, additional, Cheng, Liang, additional, Tian, Xiaocao, additional, Zhang, Hua, additional, Zhai, Yaoming, additional, Ning, Feng, additional, Sun, Xiaohui, additional, Li, Feifei, additional, Lv, Silu, additional, Wang, Junzheng, additional, Hou, Wei, additional, Sun, Wei, additional, Yan, Shichun, additional, Cui, Xiaoming, additional, Wang, Chi, additional, Wu, Zhenyuan, additional, Li, Yanjie, additional, Kang, Quan, additional, Luo, Huiming, additional, Ou, Tingting, additional, Zheng, Xiangyang, additional, Guo, Zhendong, additional, Wu, Shukuan, additional, Li, Yilei, additional, Li, Huimei, additional, Wu, Ming, additional, Zhou, Yonglin, additional, Zhou, Jinyi, additional, Tao, Ran, additional, Yang, Jie, additional, Su, Jian, additional, Liu, Fang, additional, Hu, Yihe, additional, Lu, Yan, additional, Ma, Liangcai, additional, Tang, Aiyu, additional, Zhang, Shuo, additional, Jin, Jianrong, additional, Liu, Jingchao, additional, Lin, Mei, additional, Lu, Zhenzhen, additional, Zhou, Lifang, additional, Xie, Changping, additional, Lan, Jian, additional, Zhu, Tingping, additional, Liu, Yun, additional, Wei, Liuping, additional, Zhou, Liyuan, additional, Chen, Ningyu, additional, Qin, Yulu, additional, Wang, Sisi, additional, Wu, Xianping, additional, Zhang, Ningmei, additional, Chen, Xiaofang, additional, Chang, Xiaoyu, additional, Yuan, Mingqiang, additional, Wu, Xia, additional, Jiang, Wei, additional, Liu, Jiaqiu, additional, Sun, Qiang, additional, Chen, Faqing, additional, Ren, Xiaolan, additional, Dong, Caixia, additional, Zhang, Hui, additional, Mao, Enke, additional, Wang, Xiaoping, additional, Wang, Tao, additional, Zhang, Xi, additional, Kang, Kai, additional, Feng, Shixian, additional, Tian, Huizi, additional, Fan, Lei, additional, Li, XiaoLin, additional, Sun, Huarong, additional, He, Pan, additional, Zhang, Xukui, additional, Yu, Min, additional, Hu, Ruying, additional, Wang, Hao, additional, Zhang, Xiaoyi, additional, Cao, Yuan, additional, Xie, Kaixu, additional, Chen, Lingli, additional, Shen, Dun, additional, Li, Xiaojun, additional, Jin, Donghui, additional, Yin, Li, additional, Liu, Huilin, additional, Fu, Zhongxi, additional, Xu, Xin, additional, Zhang, Hao, additional, Chen, Jianwei, additional, Peng, Yuan, additional, Zhang, Libo, additional, and Qu, Chan, additional

Published
2023
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15. Protein-truncating variants inBSNare associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease

Author

Zhao, Yajie, primary, Chukanova, Maria, additional, Kentistou, Katherine A, additional, Fairhurst-Hunter, Zammy, additional, Siegert, Anna Maria, additional, Jia, Raina, additional, Dowsett, Georgina, additional, Gardner, Eugene J, additional, Day, Felix R, additional, Kaisinger, Lena R, additional, Tung, Yi-Chun Loraine, additional, Hong Lam, Brian Yee, additional, Chen, Hsiao-Jou Cortina, additional, Wang, Quanli, additional, Berumen-Campos, Jaime, additional, Kuri-Morales, Pablo, additional, Tapia-Conyer, Roberto, additional, Alegre-Diaz, Jesus, additional, Emberson, Jonathan, additional, Torres, Jason M, additional, Collins, Rory, additional, Saleheen, Danish, additional, Smith, Katherine R, additional, Paul, Dirk S, additional, Merkle, Florian, additional, Wareham, Nick J, additional, Petrovski, Slavé, additional, O’Rahilly, Steve, additional, Ong, Ken K, additional, Yeo, Giles S H, additional, and Perry, John R B, additional

Published
2023
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16. Protein-truncating variants in BSNare associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease

Author

Zhao, Yajie, Chukanova, Maria, Kentistou, Katherine A., Fairhurst-Hunter, Zammy, Siegert, Anna Maria, Jia, Raina Y., Dowsett, Georgina K. C., Gardner, Eugene J., Lawler, Katherine, Day, Felix R., Kaisinger, Lena R., Tung, Yi-Chun Loraine, Lam, Brian Yee Hong, Chen, Hsiao-Jou Cortina, Wang, Quanli, Berumen-Campos, Jaime, Kuri-Morales, Pablo, Tapia-Conyer, Roberto, Alegre-Diaz, Jesus, Barroso, Inês, Emberson, Jonathan, Torres, Jason M., Collins, Rory, Saleheen, Danish, Smith, Katherine R., Paul, Dirk S., Merkle, Florian, Farooqi, I. Sadaf, Wareham, Nick J., Petrovski, Slavé, O’Rahilly, Stephen, Ong, Ken K., Yeo, Giles S. H., and Perry, John R. B.

Abstract

Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSNand APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSNand APBA1were not associated with normal variation in childhood adiposity. Furthermore, BSNprotein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large in BSNPTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSNPTV carriers as well as the functional consequences of BSNdeletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity.

Published
2024
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17. Additional file 3 of Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality

Author

O’Loughlin, Jessica, Casanova, Francesco, Fairhurst-Hunter, Zammy, Hughes, Amanda, Bowden, Jack, Watkins, Edward R., Freathy, Rachel M., Millwood, Iona Y., Lin, Kuang, Chen, Zhengming, Li, Liming, Lv, Jun, Walters, Robin G., Howe, Laura D., Kuchenbaecker, Karoline, and Tyrrell, Jessica

Abstract

Additional file 3: Fig. S1. Observational and genetic associationsbetween WHR and depressive symptoms. Fig. S2. The genetic 1-sample MR estimatesof BMI to depressive symptoms stratified by sex and region. Fig. S3. Thegenetic 1-sample MR estimates of BMI to major depression stratified by sex andregion. Figs. S4-S8. Scatter plots of SNP-depression outcome vs. SNP-BMI2-sample MR analyses. Figs. S9-S13. Scatter plots of SNP-depression outcome vs.SNP-WHR 2-sample MR analyses.

Published
2023
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18. Additional file 1 of Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality

Author

O’Loughlin, Jessica, Casanova, Francesco, Fairhurst-Hunter, Zammy, Hughes, Amanda, Bowden, Jack, Watkins, Edward R., Freathy, Rachel M., Millwood, Iona Y., Lin, Kuang, Chen, Zhengming, Li, Liming, Lv, Jun, Walters, Robin G., Howe, Laura D., Kuchenbaecker, Karoline, and Tyrrell, Jessica

Abstract

Additional file 1: Supplementary methods.

Published
2023
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19. Causal relevance of different blood pressure traits on risk of cardiovascular diseases: GWAS and Mendelian randomisation in 100,000 Chinese adults

Author

Pozarickij, Alfred, primary, Gan, Wei, additional, Lin, Kuang, additional, Clarke, Robert, additional, Fairhurst-Hunter, Zammy, additional, Koido, Masaru, additional, Kanai, Masahiro, additional, Okada, Yukinori, additional, Kamatani, Yoichiro, additional, Guo, Yu, additional, Bennett, Derrick, additional, Du, Huaidong, additional, Chen, Yiping, additional, Yang, Ling, additional, Avery, Daniel, additional, Yu, Min, additional, Yu, Canqing, additional, Valle, Dan Schmidt, additional, Lv, Jun, additional, Chen, Junshi, additional, Peto, Richard, additional, Collins, Rory, additional, Li, Liming, additional, Chen, Zhengming, additional, Millwood, Iona Y, additional, and Walters, Robin G, additional

Published
2023
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20. Trans-ancestry meta-analysis improves performance of genetic scores for multiple adiposity-related traits in East Asian populations

Author

Walters, Robin, primary, Fairhurst-Hunter, Zammy, additional, Lin, Kuang, additional, Millwood, Iona, additional, Pozarickij, Alfred, additional, Chen, Tzu-Ting, additional, Torres, Jason M., additional, Luan, Jian'an, additional, Kartsonaki, Christiana, additional, Gan, Wei, additional, Mahajan, Anubha, additional, Du, Huaidong, additional, Sohoni, Rajani, additional, Guo, Yu, additional, Sansome, Sam, additional, Yang, Ling, additional, Yu, Canqing, additional, Chen, Yiping, additional, Lv, Jun, additional, Hemani, Gibran, additional, Koido, Masaru, additional, Kamatani, Yoichiro, additional, Spracklen, Cassandra, additional, Gordon-Larsen, Penny, additional, Koprulu, Mine, additional, Meng, Xiangrui, additional, Kuchenbaecker, Karoline, additional, Fatumo, Segun, additional, Bhatta, Laxmi, additional, Brumpton, Ben, additional, Alegre-Diaz, Jesus, additional, Kuri-Morales, Pablo, additional, Tapia-Conyer, Roberto, additional, Graham, Sarah, additional, Willer, Cristen, additional, Neville, Matthew, additional, Karpe, Fredrik, additional, Graff, Mariaelisa, additional, North, Kari, additional, Loos, Ruth, additional, Haiman, Christopher, additional, Peters, Ulrike, additional, Buyske, Steven, additional, Gignoux, Christopher, additional, Wojcik, Genevieve, additional, Lin, Yen-Feng, additional, Li, Liming, additional, McCarthy, Mark, additional, Chen, Zhengming, additional, and Holmes, Michael, additional

Published
2022
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21. Trans-ancestry meta-analysis improves performance of genetic scores for multiple adiposity-related traits in East Asian populations

Author

Fairhurst-Hunter, Zammy, primary, Lin, Kuang, additional, Millwood, Iona Y, additional, Pozarickij, Alfred, additional, Chen, Tzu-Ting, additional, Torres, Jason M, additional, Luan, Jian-an, additional, Kartsonaki, Christiana, additional, Gan, Wei, additional, Mahajan, Anubha, additional, Du, Huaidong, additional, Sohoni, Rajani, additional, Guo, Yu, additional, Sansome, Sam, additional, Yang, Ling, additional, Yu, Canqing, additional, Chen, Yiping, additional, Lv, Jun, additional, Hemani, Gibran, additional, Koido, Masaru, additional, Kamatani, Yoichiro, additional, Spracklen, Cassandra N, additional, Gordon-Larsen, Penny, additional, Koprulu, Mine, additional, Meng, Xiangrui, additional, Kuchenbaecker, Karoline, additional, Fatumo, Segun, additional, Bhatta, Laxmi, additional, Brumpton, Ben, additional, Alegre-Diaz, Jesus, additional, Kuri-Morales, Pablo, additional, Tapia-Conyer, Roberto, additional, Graham, Sarah E, additional, Willer, Cristen J, additional, Neville, Matt J, additional, Karpe, Fredrik, additional, Graff, Mariaelisa, additional, North, Kari E., additional, Loos, Ruth J.F., additional, Haiman, Christopher A., additional, Peters, Ulrike, additional, Buskye, Steve, additional, Gignoux, Christopher R., additional, Wojcik, Genevieve, additional, Lin, Yen-Feng, additional, Li, Liming, additional, McCarthy, Mark I, additional, Chen, Zhengming, additional, Holmes, Michael V, additional, and Walters, Robin G, additional

Published
2022
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22. Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie

Abstract

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

Published
2022

23. Associations of Adiposity, Circulating Protein Biomarkers, and Risk of Major Vascular Diseases

Author

Pang, Yuanjie, primary, Kartsonaki, Christiana, additional, Lv, Jun, additional, Fairhurst-Hunter, Zammy, additional, Millwood, Iona Y., additional, Yu, Canqing, additional, Guo, Yu, additional, Chen, Yiping, additional, Bian, Zheng, additional, Yang, Ling, additional, Chen, Junshi, additional, Clarke, Robert, additional, Walters, Robin G., additional, Holmes, Michael V., additional, Li, Liming, additional, and Chen, Zhengming, additional

Published
2021
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24. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., Hingorani, Aroon D., Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.

Abstract

Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

Published
2019
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25. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Planningssecretariaat HCK, Onderzoek Precision medicine, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Brain, Cancer, Cardiovasculaire Epidemiologie, Epi Methoden Team 6, Aios en Stafsecr. Cardiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, Team Medisch, Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, Van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, Van Der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'An, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., De Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Van Der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-Van Der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Roussel, Ronan, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Björn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., Hingorani, Aroon D., Planningssecretariaat HCK, Onderzoek Precision medicine, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Brain, Cancer, Cardiovasculaire Epidemiologie, Epi Methoden Team 6, Aios en Stafsecr. Cardiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, Team Medisch, Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, Van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, Van Der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'An, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., De Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Van Der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-Van Der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Roussel, Ronan, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Björn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.

Published
2019

26. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Schmidt, Amand F, primary, Holmes, Michael V, additional, Preiss, David, additional, Swerdlow, Daniel, additional, Denaxas, Spiros, additional, Fatemifar, Ghazaleh, additional, Faraway, Rupert, additional, Finan, Chris, additional, Lumbers, Tom, additional, Henry, Albert, additional, Valentine, Dennis, additional, Fairhurst-Hunter, Zammy, additional, Hartwig, Fernando Pires, additional, Horta, Bernardo Lessa, additional, Hypponen, Elina, additional, Power, Christine, additional, Moldovan, Max, additional, van Iperen, Erik, additional, Hovingh, Kees, additional, Demuth, Ilja, additional, Norman, Kristina, additional, Steinhagen-Thiessen, Elisabeth, additional, Demuth, Juri, additional, Bertram, Lars, additional, Lill, Christina M, additional, Coassin, Stefan, additional, Willeit, Johann, additional, Kiechl, Stefan, additional, Willeit, Karin, additional, Mason, Dan, additional, Wright, John, additional, Morris, Richard, additional, Wanamethee, Goya, additional, Whincup, Peter, additional, Ben-Shlomo, Yoav, additional, McLachlan, Stela, additional, Price, Jackie F., additional, Kivimaki, Mika, additional, Welch, Catherine, additional, Sanchez-Galvez, Adelaida, additional, Marques-Vidal, Pedro, additional, Nicolaides, Andrew, additional, Panayiotou, Andrie G., additional, Onland-Moret, N. Charlotte, additional, van der Schouw, Yvonne T., additional, Matullo, Giuseppe, additional, Fiorito, Giovanni, additional, Guarrera, Simonetta, additional, Sacerdote, Carlotta, additional, Wareham, Nicholas J, additional, Langenberg, Claudia, additional, Scott, Robert A, additional, Luan, Jian’an, additional, Bobak, Martin, additional, Malyutina, Sofia, additional, Pajak, Andrzej, additional, Kubinova, Ruzena, additional, Tamosiunas, Abdonas, additional, Pikhart, Hynek, additional, Grarup, Niels, additional, Pedersen, Oluf, additional, Hansen, Torben, additional, Linneberg, Allan, additional, Jess, Tine, additional, Cooper, Jackie, additional, Humphries, Steve E, additional, Brilliant, Murray, additional, Kitchner, Terrie, additional, Hakonarson, Hakon, additional, Carrell, David S., additional, McCarty, Catherine A., additional, Lester, Kirchner H, additional, Larson, Eric B., additional, Crosslin, David R., additional, Andrade, Mariza de, additional, Roden, Dan M, additional, Denny, Joshua C, additional, Carty, Cara, additional, Hancock, Stephen, additional, Attia, John, additional, Holliday, Elizabeth, additional, Scott, Rodney, additional, Schofield, Peter, additional, O’Donnell, Martin, additional, Yusuf, Salim, additional, Chong, Michael, additional, Pare, Guillaume, additional, van der Harst, Pim, additional, Said, M. Abdullah, additional, Eppinga, Ruben N., additional, Verweij, Niek, additional, Snieder, Harold, additional, Christen, Tim, additional, Mook-Kanamori, D.O., additional, Gustafsson, Stefan, additional, Lind, Lars, additional, Ingelsson, Erik, additional, Pazoki, Raha, additional, Franco, Oscar, additional, Hofman, Albert, additional, Uitterlinden, Andre, additional, Dehghan, Abbas, additional, Teumer, Alexander, additional, Baumeister, Sebastian, additional, Dörr, Marcus, additional, Lerch, Markus M., additional, Völker, Uwe, additional, Völzke, Henry, additional, Ward, Joey, additional, Pell, Jill P, additional, Meade, Tom, additional, Christophersen, Ingrid E., additional, Maitland-van der Zee, Anke H., additional, Baranova, Ekaterina V., additional, Young, Robin, additional, Ford, Ian, additional, Campbell, Archie, additional, Padmanabhan, Sandosh, additional, Bots, Michiel L, additional, Grobbee, Diederick E., additional, Froguel, Philippe, additional, Thuillier, Dorothée, additional, Roussel, Ronan, additional, Bonnefond, Amelie, additional, Cariou, Bertrand, additional, Smart, Melissa, additional, Bao, Yanchun, additional, Kumari, Meena, additional, Mahajan, Anubha, additional, Hopewell, Jemma C., additional, Seshadri, Sudha, additional, Dale, Caroline, additional, Costa, Rui Providencia E, additional, Ridker, Paul M, additional, Chasman, Daniel I., additional, Reiner, Alex P., additional, Ritchie, Marylyn D, additional, Lange, Leslie A, additional, Cornish, Alex J., additional, Dobbins, Sara E., additional, Hemminki, Kari, additional, Kinnersley, Ben, additional, Sanson, Marc, additional, Labreche, Karim, additional, Simon, Matthias, additional, Bondy, Melissa, additional, Law, Philip, additional, Speedy, Helen, additional, Allan, James, additional, Li, Ni, additional, Went, Molly, additional, Weinhold, Niels, additional, Morgan, Gareth, additional, Sonneveld, Pieter, additional, Nilsson, Björn, additional, Goldschmidt, Hartmut, additional, Sud, Amit, additional, Engert, Andreas, additional, Hansson, Markus, additional, Hemingway, Harry, additional, Asselbergs, Folkert W, additional, Patel, Riyaz S, additional, Keating, Brendan J, additional, Sattar, Naveed, additional, Houlston, Richard, additional, Casas, Juan P, additional, and Hingorani, Aroon D, additional

Published
2018
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27. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

Author

Schmidt, Amand F., Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik Pa, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard W, Wanamethee, Goya, Whincup, Peter H, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew N., Panayiotou, Andrie G., Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A, Luan, Jian'an, Smith, Daniel J, Maitland-van der Zee, Anke H, Baranova, Ekaterina V, LifeLines Cohort Study Group, Schmidt, Amand F., Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik Pa, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard W, Wanamethee, Goya, Whincup, Peter H, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew N., Panayiotou, Andrie G., Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A, Luan, Jian'an, Smith, Daniel J, Maitland-van der Zee, Anke H, Baranova, Ekaterina V, and LifeLines Cohort Study Group

Abstract

BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores.FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c(0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30).INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits

Published
2017

28. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

Author

Pharmacoepidemiology and Clinical Pharmacology, Schmidt, Amand F., Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik Pa, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard W, Wanamethee, Goya, Whincup, Peter H, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew N., Panayiotou, Andrie G., Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A, Luan, Jian'an, Smith, Daniel J, Maitland-van der Zee, Anke H, Baranova, Ekaterina V, LifeLines Cohort Study Group, Pharmacoepidemiology and Clinical Pharmacology, Schmidt, Amand F., Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik Pa, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard W, Wanamethee, Goya, Whincup, Peter H, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew N., Panayiotou, Andrie G., Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A, Luan, Jian'an, Smith, Daniel J, Maitland-van der Zee, Anke H, Baranova, Ekaterina V, and LifeLines Cohort Study Group

Published
2017

29. PCSK9 genetic variants and risk of type 2 diabetes: A mendelian randomisation study

Author

UMC Utrecht, Cardiovasculaire Epi Team 3, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Brain, JC onderzoeksprogramma Kanker, Circulatory Health, Cardiovasculaire Epidemiologie, TN groep Adan, Aios en Stafsecr. Cardiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, Cardiologie, Team Medisch, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O., Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Balkau, Beverley, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., Sattar, Naveed, UMC Utrecht, Cardiovasculaire Epi Team 3, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Brain, JC onderzoeksprogramma Kanker, Circulatory Health, Cardiovasculaire Epidemiologie, TN groep Adan, Aios en Stafsecr. Cardiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, Cardiologie, Team Medisch, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O., Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Balkau, Beverley, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., and Sattar, Naveed

Published
2017

30. PCSK9 genetic variants and risk of type 2 diabetes:a mendelian randomisation study

Author

Schmidt, Amand F, Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S, Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Schmidt, Amand F, Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S, Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, and Linneberg, Allan

Abstract

BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores.FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m(2), -0·09 to 0·30).INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benef

Published
2017

32. PCSK9genetic variants and risk of type 2 diabetes: a mendelian randomisation study

Author

Schmidt, Amand F, Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S, Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pająk, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E, Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S, McCarty, Catherine A, Kirchner, H Lester, Larson, Eric B, Crosslin, David R, de Andrade, Mariza, Roden, Dan M, Denny, Joshua C, Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M Abdullah, Eppinga, Ruben N, Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O, Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M, Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P, Smith, Daniel J, Meade, Tom, Maitland-van der Zee, Anke H, Baranova, Ekaterina V, Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L, Grobbee, Diederick E, Froguel, Philippe, Thuillier, Dorothée, Balkau, Beverley, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M, Chasman, Daniel I, Reiner, Alex P, Lange, Leslie A, Ritchie, Marylyn D, Asselbergs, Folkert W, Casas, Juan-Pablo, Keating, Brendan J, Preiss, David, Hingorani, Aroon D, and Sattar, Naveed

Abstract

Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.

Published
2017
Full Text
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33. A wide landscape of morbidity and mortality risk associated with marital status in 0·5 million Chinese men and women: a prospective cohort study

Author

Xiao, Meng, Li, Aolin, Wang, Yueqing, Yu, Canqing, Pang, Yuanjie, Pei, Pei, Yang, Ling, Chen, Yiping, Du, Huaidong, Schmidt, Dan, Avery, Daniel, Sun, Qiang, Chen, Junshi, Chen, Zhengming, Li, Liming, Lv, Jun, Sun, Dianjianyi, Chen, Junshi, Chen, Zhengming, Clarke, Robert, Collins, Rory, Guo, Yu, Li, Liming, Lv, Jun, Peto, Richard, Walters, Robin, Avery, Daniel, Bennett, Derrick, Boxall, Ruth, Burgess, Sue, Chan, Ka Hung, Chang, Yumei, Chen, Yiping, Chen, Zhengming, Clarke, Johnathan, Clarke, Robert, Du, Huaidong, Mohamed, Ahmed Edris, Fairhurst-Hunter, Zammy, Fry, Hannah, Hill, Mike, Holmes, Michael, Im, Pek Kei, Iona, Andri, Kakkoura, Maria, Kartsonaki, Christiana, Kerosi, Rene, Lin, Kuang, Mazidi, Mohsen, Millwood, Iona, Morris, Sam, Nie, Qunhua, Pozarickij, Alfred, Ryder, Paul, Said, Saredo, Schmidt, Dan, Sherliker, Paul, Stevens, Becky, Turnbull, Iain, Walters, Robin, Wang, Lin, Wright, Neil, Yang, Ling, Yang, Xiaoming, Yao, Pang, Guo, Yu, Han, Xiao, Hou, Can, Lv, Jun, Pei, Pei, Liu, Chao, Yu, Canqing, Xia, Qingmei, Pang, Zengchang, Gao, Ruqin, Li, Shanpeng, Duan, Haiping, 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, Sun, Wei, Yan, Shichun, Cui, Xiaoming, Wang, Chi, Wu, Zhenyuan, Li, Yanjie, Kang, Quan, Luo, Huiming, Ou, Tingting, Zheng, Xiangyang, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, 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, Lin, Mei, Lu, Zhenzhen, Zhou, Lifang, Xie, Changping, Lan, Jian, Zhu, Tingping, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Chen, Ningyu, Qin, Yulu, Wang, Sisi, Wu, Xianping, Zhang, Ningmei, Chen, Xiaofang, Chang, Xiaoyu, Yuan, Mingqiang, Wu, Xia, Chen, Xiaofang, Jiang, Wei, Liu, Jiaqiu, Sun, Qiang, Chen, Faqing, Ren, Xiaolan, Dong, Caixia, Zhang, Hui, Mao, Enke, Wang, Xiaoping, Wang, Tao, zhang, Xi, Kang, Kai, Feng, Shixian, Tian, Huizi, Fan, Lei, Li, XiaoLin, Sun, Huarong, He, Pan, Zhang, Xukui, Yu, Min, Hu, Ruying, Wang, Hao, Zhang, Xiaoyi, Cao, Yuan, Xie, Kaixu, Chen, Lingli, Shen, Dun, Li, Xiaojun, Jin, Donghui, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Xin, Zhang, Hao, Chen, Jianwei, Peng, Yuan, Zhang, Libo, and Qu, Chan

Abstract

A comprehensive depiction of long-term health impacts of marital status is lacking.

Published
2023
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34. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, Van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, Van Der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian’an, Bobak, Martin, Malyutina, Sofia, Pająk, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., De Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O’Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Van Der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-Van Der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Roussel, Ronan, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Björn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.

Subjects
Genetic association studies, LDL-cholesterol, Phenome-wide association scan, Mendelian randomisation, Coronary artery disease, 3. Good health, Research Article
Abstract

Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

35. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Schmidt, Amand F, Holmes, Michael V, Preiss, David, Swerdlow, Daniel I, Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, Van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin Christine, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, Van Der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert A, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pająk, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E, Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S, McCarty, Catherine A, Lester, Kirchner H, Larson, Eric B, Crosslin, David R, De Andrade, Mariza, Roden, Dan M, Denny, Joshua C, Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Van Der Harst, Pim, Said, M Abdullah, Eppinga, Ruben N, Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D O, Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M, Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P, Meade, Tom, Christophersen, Ingrid E, Maitland-Van Der Zee, Anke H, Baranova, Ekaterina V, Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L, Grobbee, Diederick E, Froguel, Philippe, Thuillier, Dorothée, Roussel, Ronan, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C, Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E, Ridker, Paul M, Chasman, Daniel I, Reiner, Alex P, Ritchie, Marylyn D, Lange, Leslie A, Cornish, Alex J, Dobbins, Sara E, Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Björn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W, Patel, Riyaz S, Keating, Brendan J, Sattar, Naveed, Houlston, Richard, Casas, Juan P, and Hingorani, Aroon D

Subjects
610 Medicine & health, 3. Good health
Abstract

BACKGROUND We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

36. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Schmidt, Amand F, Holmes, Michael V, Preiss, David, Swerdlow, Daniel I, Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, Van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, Van Der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert A, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pająk, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E, Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S, McCarty, Catherine A, Lester, Kirchner H, Larson, Eric B, Crosslin, David R, De Andrade, Mariza, Roden, Dan M, Denny, Joshua C, Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Van Der Harst, Pim, Said, M Abdullah, Eppinga, Ruben N, Verweij, Niek, Snieder, Harold, Lifelines Cohort Authors, Christen, Tim, Mook-Kanamori, DO, ICBP Consortium, Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M, Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P, Meade, Tom, Christophersen, Ingrid E, Maitland-Van Der Zee, Anke H, Baranova, Ekaterina V, Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L, Grobbee, Diederick E, Froguel, Philippe, Thuillier, Dorothée, Roussel, Ronan, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C, Seshadri, Sudha, METASTROKE Consortium Of The ISGC, Dale, Caroline, Costa, Rui Providencia E, Ridker, Paul M, Chasman, Daniel I, Reiner, Alex P, Ritchie, Marylyn D, Lange, Leslie A, Cornish, Alex J, Dobbins, Sara E, Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Björn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W, Patel, Riyaz S, Keating, Brendan J, Sattar, Naveed, Houlston, Richard, Casas, Juan P, and Hingorani, Aroon D

Subjects
Genetic association studies, Serine Proteinase Inhibitors, Anticholesteremic Agents, PCSK9 Inhibitors, Myocardial Infarction, Down-Regulation, Cholesterol, LDL, Polymorphism, Single Nucleotide, Risk Assessment, 3. Good health, Brain Ischemia, Stroke, Treatment Outcome, Risk Factors, LDL-cholesterol, Humans, Phenome-wide association scan, Proprotein Convertase 9, Mendelian randomisation, Biomarkers, Dyslipidemias, Genome-Wide Association Study, Randomized Controlled Trials as Topic
Abstract

BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

37. The Genetic Architecture of Depression in Individuals of East Asian Ancestry

Author

Giannakopoulou, Olga, Lin, Kuang, Meng, Xiangrui, Su, Mei-Hsin, Kuo, Po-Hsiu, Peterson, Roseann E., Awasthi, Swapnil, Moscati, Arden, Coleman, Jonathan R. I., Bass, Nick, Millwood, Iona Y., Chen, Yiping, Chen, Zhengming, Chen, Hsi-Chung, Lu, Mong-Liang, Huang, Ming-Chyi, Chen, Chun-Hsin, Stahl, Eli A., Loos, Ruth J. F., Mullins, Niamh, Ursano, Robert J., Kessler, Ronald C., Stein, Murray B., Sen, Srijan, Scott, Laura J., Burmeister, Margit, Fang, Yu, Tyrrell, Jess, Jiang, Yunxuan, Tian, Chao, McIntosh, Andrew M., Ripke, Stephan, Dunn, Erin C., Kendler, Kenneth S., Walters, Robin G., Lewis, Cathryn M., Kuchenbaecker, Karoline, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Colodro-Conde, Lucía, Coon, Hilary, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Howard, David M., Hougaard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., Luykx, Jurjen J., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Pettersson, Erik, Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thompson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T, Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, EJC, DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela AF, Magnusson, Patrik K., Martin, Nicholas G., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M., O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda WJH, Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Agee, Michelle, Aslibekyan, Stella, Auton, Adam, Babalola, Elizabeth, Bell, Robert K., Bielenberg, Jessica, Bryc, Katarzyna, Bullis, Emily, Cameron, Briana, Coker, Daniella, Cuellar Partida, Gabriel, Dhamija, Devika, Das, Sayantan, Elson, Sarah L., Filshtein, Teresa, Fletez-Brant, Kipper, Fontanillas, Pierre, Freyman, Will, Gandhi, Pooja M., Heilbron, Karl, Hicks, Barry, Hinds, David A., Huber, Karen E., Jewett, Ethan M., Kleinman, Aaron, Kukar, Katelyn, Lane, Vanessa, Lin, Keng-Han, Lowe, Maya, Luff, Marie K., McCreight, Jennifer C., McIntyre, Matthew H., McManus, Kimberly F., Micheletti, Steven J., Moreno, Meghan E., Mountain, Joanna L., Mozaffari, Sahar V., Nandakumar, Priyanka, Noblin, Elizabeth S., O'Connell, Jared, Petrakovitz, Aaron A., Poznik, G. David, Schumacher, Morgan, Shastri, Anjali J., Shelton, Janie F., Shi, Jingchunzi, Shringarpure, Suyash, Tran, Vinh, Tung, Joyce Y., Wang, Xin, Wang, Wei, Weldon, Catherine H., Wilton, Peter, Avery, Daniel, Bennett, Derrick, Bian, Zheng, Boxall, Ruth, Bragg, Fiona, Chan, Ka Hung, Chang, Liang, Chang, Yumei, Chen, Biyun, Chen, Jinyan, Chen, Junshi, Chen, Naying, Chen, Ningyu, Chen, Xiaofang, Cheng, Liang, Clarke, Johnathan, Clarke, Robert, Collins, Rory, Dong, Caixia, Du, Huaidong, Du, Ranran, Fairhurst-Hunter, Zammy, Fan, Lei, Feng, Shixian, Fu, Zhongxi, Gan, Wei, Gao, Ruqin, Gao, Yulian, Ge, Pengfei, Gilbert, Simon, Gong, Weiwei, Gu, Qijun, Guo, Yu, Guo, Zhendong, Guo, Ziyan, Hacker, Alex, Han, Xiao, Hariri, Parisa, He, Pan, He, Tianyou, Hill, Mike, Holmes, Michael, Hou, Can, Hou, Wei, Hu, Chen, Hu, Ruying, Hu, Ximin, Hu, Yihe, Hua, Hua, Hua, Yujie, Huang, Yuelong, Im, Pek Kei, Iona, Andri, Jiang, Qilian, Jin, Jianrong, Kakkoura, Maria, Kang, Quan, Kartsonaki, Christiana, Kerosi, Rene, Kong, Ling, Lan, Jian, Lancaster, Garry, Li, Feifei, Li, Huimei, Li, Jianguo, Li, Liming, Li, Mingqiang, LI, Shanpeng, Li, Yanjie, Li, Yilei, Li, Zhongxiao, Lingli, Lingli, Liu, Chao, Liu, Depei, Liu, Duo, Liu, Fang, Liu, Huilin, Liu, Jiaqiu, Liu, Jingchao, Liu, Yongmei, Liu, Yun, Long, Huajun, Lu, Yan, Luo, Guojin, Lv, Jun, Lv, Silu, Ma, Liangcai, Mao, Enke, McDonnell, John, Meng, Fanwen, Meng, Jinhuai, Millwood, Iona, Nie, Qunhua, Ning, Feng, Pan, Dongxia, Pan, Rong, Pang, Zengchang, Pei, Pei, Peto, Richard, Pozarickij, Alfred, Qian, Yijian, Qin, Yulu, Qu, Chan, Ren, Xiaolan, Ryder, Paul, Sansome, Sam, Schmidt, Dan, Sherliker, Paul, Sohoni, Rajani, Stevens, Becky, Su, Jian, Sun, Huarong, Sun, Qiang, Sun, Xiaohui, Tang, Aiyu, Tang, Zhenzhu, Tao, Ran, Tian, Xiaocao, Turnbull, Iain, Walters, Robin, Wan, Meng, Wang, Chunmei, Wang, Chen, Wang, Hao, Wang, Junzheng, Wang, Lin, Wang, Ping, Wang, Tao, Wang, Shaojie, Wang, Sisi, Wang, Xiaohuan, Wei, Liuping, Weng, Min, Wright, Neil, Wu, Ming, Wu, Xianping, Wu, Shukuan, Xie, Kaixu, Xu, Qiaohua, Xu, Qinai, Xu, Xin, Yan, Shichun, Yang, Ling, Yang, Xiaoming, Yang, Jie, Yao, Pang, Yin, Li, Yu, Bo, Yu, Canqing, Yu, Min, Zhai, Yaoming, Zhang, Hao, Zhang, Hui, Zhang, Jun, Zhang, Libo, Zhang, Ningmei, Zhang, Xi, Zhang, Xiaoyi, Zhang, Xukui, Zhong, Xunfu, Zhou, Ding Zhang, Zhou, Gang, Zhou, Jinyi, Zhou, Liyuan, Zhou, Weiwei, Zhou, Xue, Zhou, Yonglin, and Zou, Mingyuan

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38. Publisher Correction : Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, He, Yunye, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Georgakis, Marios K, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Caro, Ilana, Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Krebs, Kristi, Wilson, Peter W F, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Consortium, COMPASS, Consortium, INVENT, Initiative, Dutch Parelsnoer, Biobank, Estonian, Consortium, PRECISE4Q, Consortium, FinnGen, Liaw, Yi-Ching, Network, NINDS Stroke Genetics, Consortium, MEGASTROKE, Consortium, SIREN, Group, China Kadoorie Biobank Collaborative, Program, VA Million Veteran, Consortium, International Stroke Genetics, Japan, Biobank, Consortium, CHARGE, Consortium, GIGASTROKE, Millwood, Iona Y, Vaura, Felix C, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M M, Lin, Kuang, Irvin, Marguerite R, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Winsvold, Bendik Slagsvold, Kõrv, Janika, França, Paulo H C, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas G., Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Srinivasasainagendra, Vinodh, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Anderson, Christopher D, Zwart, John-Anker, Niiranen, Teemu J, Parodi, Livia, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Hachiya, Tsuyoshi, Bae, Hee-Joon, Dichgans, Martin, Debette, Stephanie, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Jürgenson, Tuuli, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Namba, Shinichi, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Posner, Daniel C, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Kamanu, Frederick K, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Koido, Masaru, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Le Grand, Quentin, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Shi, Mingyang, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Børge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Bis, Joshua C, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michèle M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-François, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke J H, Kappelle, L Jaap, Esko, Tõnu, Metspalu, Andres, Mägi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jiménez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie L M, Rannikmäe, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent N S, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engström, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibañez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muiño, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul I W, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-François, Delavaran, Hossein, Dörr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Müller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Ásgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles D A, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tárraga, Carolina, Völzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Le Grand, Quentin, Ferreira, Leslie E, Nagai, Akiko, Murakami, Yoishinori, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, van Vugt, Marion, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Völker, Uwe, de Jager, Phil L, de Cid, Rafael, Nordestgaard, Børge G, Sargurupremraj, Muralidharan, Verma, Shefali S, de Laat, Karlijn F, van Norden, Anouk G W, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul J A M, Gons, Rob A R, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank G W, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjær, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethüm, Kathrin, Gallego-Fabrega, Cristina, Lledós, Miquel, Llucià-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, José, Freijó, Marimar, Arenillas, Juan Francisco, Obach, Victor, Álvarez-Sabín, José, Molina, Carlos A, Ribó, Marc, Muñoz-Narbona, Lucia, Lopez-Cancio, Elena, Millán, Mònica, Diaz-Navarro, Rosa, Vives-Bauza, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sánchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Martí-Fàbregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet M J, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Onland-Moret, N Charlotte, and Heath, Alicia K

Subjects
Stroke, Multidisciplinary, Genetic markers, ddc:500, Predictive markers, Genome-wide association studies
Published
2022
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39. BMI and well-being in people of East Asian and European ancestry: a Mendelian randomisation study.

Author

O'Loughlin J, Casanova F, Hughes A, Fairhurst-Hunter Z, Li L, Chen Z, Bowden J, Watkins E, Freathy RM, Howe LD, Walters RG, and Tyrrell J

Subjects
Adult, Female, Humans, Male, China, Body Mass Index, East Asian People, European People, Health Status
Abstract

Previous studies have linked higher body mass index (BMI) to lower subjective well-being in adult European ancestry populations. However, our understanding of these relationships across different populations is limited. Here, we investigated the association between BMI and well-being in people of (a) East Asian and (b) European ancestry in the China Kadoorie Biobank (CKB) and UK Biobank (UKB), respectively. Mendelian randomisation (MR) methods were used to test the relationship between BMI with (a) health satisfaction and (b) life satisfaction. One-sample MR enabled us to test effects in men and women separately and to test the role of cultural contexts by stratifying our analyses by urban and rural home location in both China and the UK. Further, we implemented a control function method to test the linearity of the BMI-well-being relationship. We found evidence of different associations between BMI and well-being in individuals of East Asian versus European ancestry. For example, a genetically instrumented higher BMI tentatively associated with higher health satisfaction in people of East Asian ancestry, especially in females (ß: 0.041, 95% CI: 0.002, 0.081). In contrast, there was a robust inverse association between higher genetically instrumented BMI and health satisfaction in all European ancestry UKB participants (ß: -0.183, 95% CI: -0.200, -0.165, P difference  < 1.00E-15). We also showed the importance of considering non-linear relationships in the MR framework by providing evidence of non-linear relationships between BMI and health and life satisfaction. Overall, our study suggests potential setting-specific causality in the relationship between BMI and subjective well-being, with robust differences observed between East Asians and Europeans when considering very similar outcomes. We highlight the importance of (a) considering potential non-linear relationships in causal analyses and (b) testing causal relationships in different populations, as the casual nature of relationships, especially relationships influenced by social processes, may be setting-specific., (© 2023. The Author(s).)

Published
2023
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40. Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality.

Author

O'Loughlin J, Casanova F, Fairhurst-Hunter Z, Hughes A, Bowden J, Watkins ER, Freathy RM, Millwood IY, Lin K, Chen Z, Li L, Lv J, Walters RG, Howe LD, Kuchenbaecker K, and Tyrrell J

Subjects
Female, Humans, Male, Body Mass Index, Mendelian Randomization Analysis, Obesity genetics, Polymorphism, Single Nucleotide genetics, China, Body Composition genetics, Depression epidemiology, Depression genetics, East Asian People, Genome-Wide Association Study
Abstract

Background: Extensive evidence links higher body mass index (BMI) to higher odds of depression in people of European ancestry. However, our understanding of the relationship across different settings and ancestries is limited. Here, we test the relationship between body composition and depression in people of East Asian ancestry., Methods: Multiple Mendelian randomisation (MR) methods were used to test the relationship between (a) BMI and (b) waist-hip ratio (WHR) with depression. Firstly, we performed two-sample MR using genetic summary statistics from a recent genome-wide association study (GWAS) of depression (with 15,771 cases and 178,777 controls) in people of East Asian ancestry. We selected 838 single nucleotide polymorphisms (SNPs) correlated with BMI and 263 SNPs correlated with WHR as genetic instrumental variables to estimate the causal effect of BMI and WHR on depression using the inverse-variance weighted (IVW) method. We repeated these analyses stratifying by home location status: China versus UK or USA. Secondly, we performed one-sample MR in the China Kadoorie Biobank (CKB) in 100,377 participants. This allowed us to test the relationship separately in (a) males and females and (b) urban and rural dwellers. We also examined (c) the linearity of the BMI-depression relationship., Results: Both MR analyses provided evidence that higher BMI was associated with lower odds of depression. For example, a genetically-instrumented 1-SD higher BMI in the CKB was associated with lower odds of depressive symptoms [OR: 0.77, 95% CI: 0.63, 0.95]. There was evidence of differences according to place of residence. Using the IVW method, higher BMI was associated with lower odds of depression in people of East Asian ancestry living in China but there was no evidence for an association in people of East Asian ancestry living in the USA or UK. Furthermore, higher genetic BMI was associated with differential effects in urban and rural dwellers within China., Conclusions: This study provides the first MR evidence for an inverse relationship between BMI and depression in people of East Asian ancestry. This contrasts with previous findings in European populations and therefore the public health response to obesity and depression is likely to need to differ based on sociocultural factors for example, ancestry and place of residence. This highlights the importance of setting-specific causality when using genetic causal inference approaches and data from diverse populations to test hypotheses. This is especially important when the relationship tested is not purely biological and may involve sociocultural factors., (© 2023. The Author(s).)

Published
2023
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41. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9.

Author

Schmidt AF, Holmes MV, Preiss D, Swerdlow DI, Denaxas S, Fatemifar G, Faraway R, Finan C, Valentine D, Fairhurst-Hunter Z, Hartwig FP, Horta BL, Hypponen E, Power C, Moldovan M, van Iperen E, Hovingh K, Demuth I, Norman K, Steinhagen-Thiessen E, Demuth J, Bertram L, Lill CM, Coassin S, Willeit J, Kiechl S, Willeit K, Mason D, Wright J, Morris R, Wanamethee G, Whincup P, Ben-Shlomo Y, McLachlan S, Price JF, Kivimaki M, Welch C, Sanchez-Galvez A, Marques-Vidal P, Nicolaides A, Panayiotou AG, Onland-Moret NC, van der Schouw YT, Matullo G, Fiorito G, Guarrera S, Sacerdote C, Wareham NJ, Langenberg C, Scott RA, Luan J, Bobak M, Malyutina S, Pająk A, Kubinova R, Tamosiunas A, Pikhart H, Grarup N, Pedersen O, Hansen T, Linneberg A, Jess T, Cooper J, Humphries SE, Brilliant M, Kitchner T, Hakonarson H, Carrell DS, McCarty CA, Lester KH, Larson EB, Crosslin DR, de Andrade M, Roden DM, Denny JC, Carty C, Hancock S, Attia J, Holliday E, Scott R, Schofield P, O'Donnell M, Yusuf S, Chong M, Pare G, van der Harst P, Said MA, Eppinga RN, Verweij N, Snieder H, Christen T, Mook-Kanamori DO, Gustafsson S, Lind L, Ingelsson E, Pazoki R, Franco O, Hofman A, Uitterlinden A, Dehghan A, Teumer A, Baumeister S, Dörr M, Lerch MM, Völker U, Völzke H, Ward J, Pell JP, Meade T, Christophersen IE, Maitland-van der Zee AH, Baranova EV, Young R, Ford I, Campbell A, Padmanabhan S, Bots ML, Grobbee DE, Froguel P, Thuillier D, Roussel R, Bonnefond A, Cariou B, Smart M, Bao Y, Kumari M, Mahajan A, Hopewell JC, Seshadri S, Dale C, Costa RPE, Ridker PM, Chasman DI, Reiner AP, Ritchie MD, Lange LA, Cornish AJ, Dobbins SE, Hemminki K, Kinnersley B, Sanson M, Labreche K, Simon M, Bondy M, Law P, Speedy H, Allan J, Li N, Went M, Weinhold N, Morgan G, Sonneveld P, Nilsson B, Goldschmidt H, Sud A, Engert A, Hansson M, Hemingway H, Asselbergs FW, Patel RS, Keating BJ, Sattar N, Houlston R, Casas JP, and Hingorani AD

Subjects
Anticholesteremic Agents adverse effects, Biomarkers blood, Brain Ischemia epidemiology, Brain Ischemia prevention & control, Down-Regulation, Dyslipidemias blood, Dyslipidemias epidemiology, Genome-Wide Association Study, Humans, Myocardial Infarction epidemiology, Myocardial Infarction prevention & control, Randomized Controlled Trials as Topic, Risk Assessment, Risk Factors, Serine Proteinase Inhibitors adverse effects, Stroke epidemiology, Stroke prevention & control, Treatment Outcome, Anticholesteremic Agents therapeutic use, Cholesterol, LDL blood, Dyslipidemias drug therapy, Dyslipidemias genetics, PCSK9 Inhibitors, Polymorphism, Single Nucleotide, Proprotein Convertase 9 genetics, Serine Proteinase Inhibitors therapeutic use
Abstract

Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9., Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration., Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable., Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

Published
2019
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