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3. Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study

Author

Zheng, Jie, Xu, Min, Yang, Qian, Hu, Chunyan, Walker, Venexia, Lu, Jieli, Wang, Jiqiu, Liu, Ruixin, Xu, Yu, Wang, Tiange, Zhao, Zhiyun, Yuan, Jinqiu, Burgess, Stephen, Au Yeung, Shiu Lun, Luo, Shan, Anderson, Emma L., Holmes, Michael V., Smith, George Davey, Ning, Guang, Wang, Weiqing, Gaunt, Tom R., and Bi, Yufang

Published
2023
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7. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids

Author

Ramdas, Shweta, Judd, Jonathan, Graham, Sarah E., Kanoni, Stavroula, Wang, Yuxuan, Surakka, Ida, Wenz, Brandon, Clarke, Shoa L., Chesi, Alessandra, Wells, Andrew, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J.M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Lee, Wen-Jane, Hsiung, Chao Agnes, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Schönherr, Sebastian, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Le, Phuong, Feitosa, Mary F., Wojczynski, Mary K., Hemerich, Daiane, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Noah, Tsao L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Emmel, Carina, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Sankareswaran, Alagu, Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R.H.J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Morgan, Anna, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R.B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, He, Karen Y., Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H.H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W.J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Ida Chen, Yii-Der, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D.C., Arnett, Donna K., Walker, Mark, Scott, Laura J., Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N.A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Lu, Fan, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, t Hart, Leen M., Elders, Petra J.M., Rader, Daniel J., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J.F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F.A., Kiemeney, Lambertus, de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., Willems van Dijk, Ko, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Huey-Herng Sheu, Wayne, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K.E., Boomsma, Dorret I., de Geus, Eco J.C., Cupples, L. Adrienne, van Meurs, Joyce B.J., Ikram, Arfan, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Tuomilehto, Jaakko, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, Y. Eugene, Ho, Yuk-Lam, Lynch, Julie A., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Struan Grant, Natarajan, Pradeep, Sun, Yan V., Morris, Andrew P., Deloukas, Panos, Peloso, Gina, Assimes, Themistocles L., Willer, Cristen J., Zhu, Xiang, and Brown, Christopher D.

Published
2022
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9. Causal inference in health and disease: a review of the principles and applications of Mendelian randomization.

Author

Lovegrove, Catherine E, Howles, Sarah A, Furniss, Dominic, and Holmes, Michael V

Abstract

Mendelian randomization (MR) is a genetic epidemiological technique that uses genetic variation to infer causal relationships between modifiable exposures and outcome variables. Conventional observational epidemiological studies are subject to bias from a range of sources; MR analyses can offer an advantage in that they are less prone to bias as they use genetic variants inherited at conception as "instrumental variables", which are proxies of an exposure. However, as with all research tools, MR studies must be carefully designed to yield valuable insights into causal relationships between exposures and outcomes, and to avoid biased or misleading results that undermine the validity of the causal inferences drawn from the study. In this review, we outline Mendel's laws of inheritance, the assumptions and principles that underlie MR, MR study designs and methods, and how MR analyses can be applied and reported. Using the example of serum phosphate concentrations on liability to kidney stone disease we illustrate how MR estimates may be visualized and, finally, we contextualize MR in bone and mineral research including exemplifying how this technique could be employed to inform clinical studies and future guidelines concerning BMD and fracture risk. This review provides a framework to enhance understanding of how MR may be used to triangulate evidence and progress research in bone and mineral metabolism as we strive to infer causal effects in health and disease. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Mendelian randomization

Author

Sanderson, Eleanor, Glymour, M. Maria, Holmes, Michael V., Kang, Hyunseung, Morrison, Jean, Munafò, Marcus R., Palmer, Tom, Schooling, C. Mary, Wallace, Chris, Zhao, Qingyuan, and Davey Smith, George

Published
2022
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13. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Author

Kanoni, Stavroula, Graham, Sarah E., Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L., Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J. M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Yousri, Noha A., Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Hwu, Chii-Min, Hung, Yi-Jen, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, EWarwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Vazquez-Moreno, Miguel, Feitosa, Mary F., Wojczynski, Mary K., Wang, Zhe, Preuss, Michael H., Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Tsao, Noah L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Frank, Mirjam, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Bayyana, Swati, Stringham, Heather M., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Nardone, Giuseppe Giovanni, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R. B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Liang, Jingjing, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, Hollander, Anneke Iden, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Costanzo, Maria C., Jang, Dongkeun, Burtt, Noël P., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, EShyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M.‘t, Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Chuang, Lee-Ming, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., Willemsen, Allegonda H. M., Cupples, LAdrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, YEugene, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter W. F., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Mohlke, Karen L., Sun, Yan V., Morris, Andrew P., Boehnke, Michael, Brown, Christopher D., Natarajan, Pradeep, Deloukas, Panos, Willer, Cristen J., Assimes, Themistocles L., and Peloso, Gina M.

Published
2022
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14. Genetic Analysis and Natural History of LRRK2 G2019S Parkinson’s Disease (P11-3.006)

Author

Kmiecik, Matthew, primary, Micheletti, Steven, additional, Coker, Daniella, additional, Heilbron, Karl, additional, Shi, Jingchunzi, additional, Stagaman, Keaton, additional, Sonmez, Teresa Filshtein, additional, Fontanillas, Pierre, additional, Shringarpure, Suyash, additional, Schloetter, Madeleine, additional, Rowbotham, Helen M., additional, Cannon, Paul, additional, Shelton, Janie, additional, Hinds, David A., additional, Tung, Joyce Y., additional, Holmes, Michael V., additional, Aslibekyan, Stella, additional, and Norcliffe-Kaufmann, Lucy, additional

Published
2024
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16. The power of genetic diversity in genome-wide association studies of lipids

Author

Graham, Sarah E., Clarke, Shoa L., Wu, Kuan-Han H., Kanoni, Stavroula, Zajac, Greg J. M., Ramdas, Shweta, Surakka, Ida, Ntalla, Ioanna, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Hwang, Mi Yeong, Han, Sohee, Narita, Akira, Choudhury, Ananyo, Bentley, Amy R., Ekoru, Kenneth, Verma, Anurag, Trivedi, Bhavi, Martin, Hilary C., Hunt, Karen A., Hui, Qin, Klarin, Derek, Zhu, Xiang, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Ruotsalainen, Sanni E., Havulinna, Aki S., Veturi, Yogasudha, Feng, QiPing, Rosenthal, Elisabeth A., Lingren, Todd, Pacheco, Jennifer Allen, Pendergrass, Sarah A., Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Hindy, George, Rasheed, Asif, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Willemsen, Gonneke, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Yao, Jie, Manichaikul, Ani, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Sidore, Carlo, Fiorillo, Edoardo, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Thuesen, Betina H., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Feitosa, Mary F., Wojczynski, Mary K., Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Kember, Rachel L., Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L., Marten, Jonathan, Schmidt, Börge, Arendt, Marina, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U., Yousri, Noha A., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Chai, Xiaoran, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Hung, Yi-Jen, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Gorski, Mathias, Brumat, Marco, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Xue, Chao, Zhang, Jifeng, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., Lee, Jiwon, van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Zimmermann, Martina E., Lee, Jong Young, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hildalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Schwander, Karen, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Highland, Heather M., Young, Kristin L., Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Nadkarni, Girish N., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, Konain Fatima, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Chen, Y. Eugene, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Jung, Bettina, Böger, Carsten A., Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Yajnik, Chittaranjan S., Mercader, Josep M., Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Lu, Fan, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Parra, Esteban J., Cruz, Miguel, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, ’t Hart, Leen M., Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Cucca, Francesco, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., de Geus, Eco J. C., Cupples, L. Adrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Justice, Anne E., Baras, Aris, Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Thorsteinsdottir, Unnur, Stefansson, Kari, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Rotimi, Charles N., Hazelhurst, Scott, Ramsay, Michèle, Trembath, Richard C., van Heel, David A., Tamiya, Gen, Yamamoto, Masayuki, Kim, Bong-Jo, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Natarajan, Pradeep, Peloso, Gina M., Brown, Christopher D., Morris, Andrew P., Assimes, Themistocles L., Deloukas, Panos, Sun, Yan V., and Willer, Cristen J.

Published
2021
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19. Meta-Analysis and Mendelian Randomization: A Review

Author

Bowden, Jack and Holmes, Michael V.

Abstract

Mendelian randomization (MR) uses genetic variants as instrumental variables to infer whether a risk factor causally affects a health outcome. Meta-analysis has been used historically in MR to combine results from separate epidemiological studies, with each study using a small but select group of genetic variants. In recent years, it has been used to combine genome-wide association study (GWAS) summary data for large numbers of genetic variants. Heterogeneity among the causal estimates obtained from multiple genetic variants points to a possible violation of the necessary instrumental variable assumptions. In this article, we provide a basic introduction to MR and the instrumental variable theory that it relies upon. We then describe how random effects models, meta-regression, and robust regression are being used to test and adjust for heterogeneity in order to improve the rigor of the MR approach.

Published
2019
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22. Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases

Author

Zheng, Jie, Haberland, Valeriia, Baird, Denis, Walker, Venexia, Haycock, Philip C., Hurle, Mark R., Gutteridge, Alex, Erola, Pau, Liu, Yi, Luo, Shan, Robinson, Jamie, Richardson, Tom G., Staley, James R., Elsworth, Benjamin, Burgess, Stephen, Sun, Benjamin B., Danesh, John, Runz, Heiko, Maranville, Joseph C., Martin, Hannah M., Yarmolinsky, James, Laurin, Charles, Holmes, Michael V., Liu, Jimmy Z., Estrada, Karol, Santos, Rita, McCarthy, Linda, Waterworth, Dawn, Nelson, Matthew R., Smith, George Davey, Butterworth, Adam S., Hemani, Gibran, Scott, Robert A., and Gaunt, Tom R.

Published
2020
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23. Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals

Author

Folkersen, Lasse, Gustafsson, Stefan, Wang, Qin, Hansen, Daniel Hvidberg, Hedman, Åsa K., Schork, Andrew, Page, Karen, Zhernakova, Daria V., Wu, Yang, Peters, James, Eriksson, Niclas, Bergen, Sarah E., Boutin, Thibaud S., Bretherick, Andrew D., Enroth, Stefan, Kalnapenkis, Anette, Gådin, Jesper R., Suur, Bianca E., Chen, Yan, Matic, Ljubica, Gale, Jeremy D., Lee, Julie, Zhang, Weidong, Quazi, Amira, Ala-Korpela, Mika, Choi, Seung Hoan, Claringbould, Annique, Danesh, John, Davey Smith, George, de Masi, Federico, Elmståhl, Sölve, Engström, Gunnar, Fauman, Eric, Fernandez, Celine, Franke, Lude, Franks, Paul W., Giedraitis, Vilmantas, Haley, Chris, Hamsten, Anders, Ingason, Andres, Johansson, Åsa, Joshi, Peter K., Lind, Lars, Lindgren, Cecilia M., Lubitz, Steven, Palmer, Tom, Macdonald-Dunlop, Erin, Magnusson, Martin, Melander, Olle, Michaelsson, Karl, Morris, Andrew P., Mägi, Reedik, Nagle, Michael W., Nilsson, Peter M., Nilsson, Jan, Orho-Melander, Marju, Polasek, Ozren, Prins, Bram, Pålsson, Erik, Qi, Ting, Sjögren, Marketa, Sundström, Johan, Surendran, Praveen, Võsa, Urmo, Werge, Thomas, Wernersson, Rasmus, Westra, Harm-Jan, Yang, Jian, Zhernakova, Alexandra, Ärnlöv, Johan, Fu, Jingyuan, Smith, J. Gustav, Esko, Tõnu, Hayward, Caroline, Gyllensten, Ulf, Landen, Mikael, Siegbahn, Agneta, Wilson, James F., Wallentin, Lars, Butterworth, Adam S., Holmes, Michael V., Ingelsson, Erik, and Mälarstig, Anders

Published
2020
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24. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials

Author

Swerdlow, Daniel I, Preiss, David, Kuchenbaecker, Karoline B, Holmes, Michael V, Engmann, Jorgen EL, Shah, Tina, Sofat, Reecha, Stender, Stefan, Johnson, Paul CD, Scott, Robert A, Leusink, Maarten, Verweij, Niek, Sharp, Stephen J, Guo, Yiran, Giambartolomei, Claudia, Chung, Christina, Peasey, Anne, Amuzu, Antoinette, Li, KaWah, Palmen, Jutta, Howard, Philip, Cooper, Jackie A, Drenos, Fotios, Li, Yun R, Lowe, Gordon, Gallacher, John, Stewart, Marlene CW, Tzoulaki, Ioanna, Buxbaum, Sarah G, van der A, Daphne L, Forouhi, Nita G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Schnabel, Renate B, Hubacek, Jaroslav A, Kubinova, Ruzena, Baceviciene, Migle, Tamosiunas, Abdonas, Pajak, Andrzej, Topor-Madry, Romanvan, Stepaniak, Urszula, Malyutina, Sofia, Baldassarre, Damiano, Sennblad, Bengt, Tremoli, Elena, de Faire, Ulf, Veglia, Fabrizio, Ford, Ian, Jukema, J Wouter, Westendorp, Rudi GJ, de Borst, Gert Jan, de Jong, Pim A, Algra, Ale, Spiering, Wilko, der Zee, Anke H Maitland-van, Klungel, Olaf H, de Boer, Anthonius, Doevendans, Pieter A, Eaton, Charles B, Robinson, Jennifer G, Duggan, David, DIAGRAM Consortium, MAGIC Consortium, Kjekshus, John, Downs, John R, Gotto, Antonio M, Keech, Anthony C, Marchioli, Roberto, Tognoni, Gianni, Sever, Peter S, Poulter, Neil R, Waters, David D, Pedersen, Terje R, Amarenco, Pierre, Nakamura, Haruo, McMurray, John JV, Lewsey, James D, Chasman, Daniel I, Ridker, Paul M, Maggioni, Aldo P, Tavazzi, Luigi, Ray, Kausik K, Seshasai, Sreenivasa Rao Kondapally, Manson, JoAnn E, Price, Jackie F, Whincup, Peter H, Morris, Richard W, Lawlor, Debbie A, Smith, George Davey, Ben-Shlomo, Yoav, Schreiner, Pamela J, Fornage, Myriam, Siscovick, David S, Cushman, Mary, Kumari, Meena, Wareham, Nick J, Verschuren, WM Monique, Redline, Susan, Patel, Sanjay R, Whittaker, John C, and Hamsten, Anders

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Clinical Trials and Supportive Activities, Clinical Research, Genetics, Nutrition, Diabetes, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Aged, Body Mass Index, Body Weight, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Type 2, Female, Genetic Testing, Humans, Hydroxymethylglutaryl CoA Reductases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Middle Aged, Polymorphism, Single Nucleotide, Randomized Controlled Trials as Topic, Risk Factors, DIAGRAM Consortium, MAGIC Consortium, InterAct Consortium, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundStatins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.MethodsWe used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis.FindingsData were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials).InterpretationThe increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.FundingThe funding sources are cited at the end of the paper.

Published
2015

26. Correction: Obesity and risk of female reproductive conditions: A Mendelian randomisation study

Author

Venkatesh, Samvida S., Ferreira, Teresa, Benonisdottir, Stefania, Rahmioglu, Nilufer, Becker, Christian M., Granne, Ingrid, Zondervan, Krina T., Holmes, Michael V., Lindgren, Cecilia M., and Wittemans, Laura B. L.

Subjects
Biological sciences
Abstract

Author(s): Samvida S. Venkatesh, Teresa Ferreira, Stefania Benonisdottir, Nilufer Rahmioglu, Christian M. Becker, Ingrid Granne, Krina T. Zondervan, Michael V. Holmes, Cecilia M. Lindgren, Laura B. L. Wittemans Reference 45 [...]

Published
2022
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27. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.

Author

Holmes, Michael V, Dale, Caroline E, Zuccolo, Luisa, Silverwood, Richard J, Guo, Yiran, Ye, Zheng, Prieto-Merino, David, Dehghan, Abbas, Trompet, Stella, Wong, Andrew, Cavadino, Alana, Drogan, Dagmar, Padmanabhan, Sandosh, Li, Shanshan, Yesupriya, Ajay, Leusink, Maarten, Sundstrom, Johan, Hubacek, Jaroslav A, Pikhart, Hynek, Swerdlow, Daniel I, Panayiotou, Andrie G, Borinskaya, Svetlana A, Finan, Chris, Shah, Sonia, Kuchenbaecker, Karoline B, Shah, Tina, Engmann, Jorgen, Folkersen, Lasse, Eriksson, Per, Ricceri, Fulvio, Melander, Olle, Sacerdote, Carlotta, Gamble, Dale M, Rayaprolu, Sruti, Ross, Owen A, McLachlan, Stela, Vikhireva, Olga, Sluijs, Ivonne, Scott, Robert A, Adamkova, Vera, Flicker, Leon, Bockxmeer, Frank M van, Power, Christine, Marques-Vidal, Pedro, Meade, Tom, Marmot, Michael G, Ferro, Jose M, Paulos-Pinheiro, Sofia, Humphries, Steve E, Talmud, Philippa J, Mateo Leach, Irene, Verweij, Niek, Linneberg, Allan, Skaaby, Tea, Doevendans, Pieter A, Cramer, Maarten J, van der Harst, Pim, Klungel, Olaf H, Dowling, Nicole F, Dominiczak, Anna F, Kumari, Meena, Nicolaides, Andrew N, Weikert, Cornelia, Boeing, Heiner, Ebrahim, Shah, Gaunt, Tom R, Price, Jackie F, Lannfelt, Lars, Peasey, Anne, Kubinova, Ruzena, Pajak, Andrzej, Malyutina, Sofia, Voevoda, Mikhail I, Tamosiunas, Abdonas, Maitland-van der Zee, Anke H, Norman, Paul E, Hankey, Graeme J, Bergmann, Manuela M, Hofman, Albert, Franco, Oscar H, Cooper, Jackie, Palmen, Jutta, Spiering, Wilko, de Jong, Pim A, Kuh, Diana, Hardy, Rebecca, Uitterlinden, Andre G, Ikram, M Arfan, Ford, Ian, Hyppönen, Elina, Almeida, Osvaldo P, Wareham, Nicholas J, Khaw, Kay-Tee, Hamsten, Anders, Husemoen, Lise Lotte N, Tjønneland, Anne, Tolstrup, Janne S, Rimm, Eric, Beulens, Joline WJ, and Verschuren, WM Monique

Subjects
InterAct Consortium, Humans, Coronary Disease, Alcohol Dehydrogenase, Genetic Markers, Models, Statistical, Alcohol Drinking, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Stroke, Mendelian Randomization Analysis, Biomarkers, General & Internal Medicine, Clinical Sciences, Public Health and Health Services
Abstract

ObjectiveTo use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.DesignMendelian randomisation meta-analysis of 56 epidemiological studies.Participants261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.Main outcome measuresOdds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.ResultsCarriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).ConclusionsIndividuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

Published
2014

28. Genetic analysis and natural history of Parkinson's disease due to the LRRK2 G2019S variant.

Author

Kmiecik, Matthew J, Micheletti, Steven, Coker, Daniella, Heilbron, Karl, Shi, Jingchunzi, Stagaman, Keaton, Sonmez, Teresa Filshtein, Fontanillas, Pierre, Shringarpure, Suyash, Wetzel, Madeleine, Rowbotham, Helen M, Cannon, Paul, Shelton, Janie F, Hinds, David A, Tung, Joyce Y, Team, 23andMe Research, Holmes, Michael V, Aslibekyan, Stella, and Norcliffe-Kaufmann, Lucy

Subjects
PARKINSON'S disease, DARDARIN, GENETIC risk score, MOVEMENT disorders, RAPID eye movement sleep, BEHAVIOR disorders
Abstract

The LRRK2 G2019S variant is the most common cause of monogenic Parkinson's disease (PD); however, questions remain regarding the penetrance, clinical phenotype and natural history of carriers. We performed a 3.5-year prospective longitudinal online study in a large number of 1286 genotyped LRRK2 G2019S carriers and 109 154 controls, with and without PD, recruited from the 23andMe Research Cohort. We collected self-reported motor and non-motor symptoms every 6 months, as well as demographics, family histories and environmental risk factors. Incident cases of PD (phenoconverters) were identified at follow-up. We determined lifetime risk of PD using accelerated failure time modelling and explored the impact of polygenic risk on penetrance. We also computed the genetic ancestry of all LRRK2 G2019S carriers in the 23andMe database and identified regions of the world where carrier frequencies are highest. We observed that despite a 1 year longer disease duration (P = 0.016), LRRK2 G2019S carriers with PD had similar burden of motor symptoms, yet significantly fewer non-motor symptoms including cognitive difficulties, REM sleep behaviour disorder (RBD) and hyposmia (all P- values ≤ 0.0002). The cumulative incidence of PD in G2019S carriers by age 80 was 49%. G2019S carriers had a 10-fold risk of developing PD versus non-carriers. This rose to a 27-fold risk in G2019S carriers with a PD polygenic risk score in the top 25% versus non-carriers in the bottom 25%. In addition to identifying ancient founding events in people of North African and Ashkenazi descent, our genetic ancestry analyses infer that the G2019S variant was later introduced to Spanish colonial territories in the Americas. Our results suggest LRRK2 G2019S PD appears to be a slowly progressive predominantly motor subtype of PD with a lower prevalence of hyposmia, RBD and cognitive impairment. This suggests that the current prodromal criteria, which are based on idiopathic PD, may lack sensitivity to detect the early phases of LRRK2 PD in G2019S carriers. We show that polygenic burden may contribute to the development of PD in the LRRK2 G2019S carrier population. Collectively, the results should help support screening programmes and candidate enrichment strategies for upcoming trials of LRRK2 inhibitors in early-stage disease. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Adiposity and risk of ischaemic and haemorrhagic stroke in 0·5 million Chinese men and women: a prospective cohort study

Author

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

Published
2018
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34. Obesity and risk of female reproductive conditions: A Mendelian randomisation study

Author

Venkatesh, Samvida S., Ferreira, Teresa, Benonisdottir, Stefania, Rahmioglu, Nilufer, Becker, Christian M., Granne, Ingrid, Zondervan, Krina T., Holmes, Michael V., Lindgren, Cecilia M., and Wittemans, Laura B. L.

Subjects
Metabolism -- Health aspects, Obesity -- Physiological aspects -- Complications and side effects, Leptin -- Physiological aspects -- Health aspects, Insulin -- Physiological aspects -- Health aspects, Infertility, Female -- Risk factors -- Development and progression, Biological sciences
Abstract

Background Obesity is observationally associated with altered risk of many female reproductive conditions. These include polycystic ovary syndrome (PCOS), abnormal uterine bleeding, endometriosis, infertility, and pregnancy-related disorders. However, the roles and mechanisms of obesity in the aetiology of reproductive disorders remain unclear. Thus, we aimed to estimate observational and genetically predicted causal associations between obesity, metabolic hormones, and female reproductive disorders. Methods and findings Logistic regression, generalised additive models, and Mendelian randomisation (MR) (2-sample, non-linear, and multivariable) were applied to obesity and reproductive disease data on up to 257,193 women of European ancestry in UK Biobank and publicly available genome-wide association studies (GWASs). Body mass index (BMI), waist-to-hip ratio (WHR), and WHR adjusted for BMI were observationally (odds ratios [ORs] = 1.02-1.87 per 1-SD increase in obesity trait) and genetically (ORs = 1.06-2.09) associated with uterine fibroids (UF), PCOS, heavy menstrual bleeding (HMB), and pre-eclampsia. Genetically predicted visceral adipose tissue (VAT) mass was associated with the development of HMB (OR [95% CI] per 1-kg increase in predicted VAT mass = 1.32 [1.06-1.64], P = 0.0130), PCOS (OR [95% CI] = 1.15 [1.08-1.23], P = 3.24 x 10.sup.-05 ), and pre-eclampsia (OR [95% CI] = 3.08 [1.98-4.79], P = 6.65 x 10.sup.-07). Increased waist circumference posed a higher genetic risk (ORs = 1.16-1.93) for the development of these disorders and UF than did increased hip circumference (ORs = 1.06-1.10). Leptin, fasting insulin, and insulin resistance each mediated between 20% and 50% of the total genetically predicted association of obesity with pre-eclampsia. Reproductive conditions clustered based on shared genetic components of their aetiological relationships with obesity. This study was limited in power by the low prevalence of female reproductive conditions among women in the UK Biobank, with little information on pre-diagnostic anthropometric traits, and by the susceptibility of MR estimates to genetic pleiotropy. Conclusions We found that common indices of overall and central obesity were associated with increased risks of reproductive disorders to heterogenous extents in a systematic, large-scale genetics-based analysis of the aetiological relationships between obesity and female reproductive conditions. Our results suggest the utility of exploring the mechanisms mediating the causal associations of overweight and obesity with gynaecological health to identify targets for disease prevention and treatment., Author(s): Samvida S. Venkatesh 1,2,*, Teresa Ferreira 1,3, Stefania Benonisdottir 1, Nilufer Rahmioglu 2,3, Christian M. Becker 3, Ingrid Granne 3, Krina T. Zondervan 2,3, Michael V. Holmes 4,5, Cecilia [...]

Published
2022
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35. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

Author

Asselbergs, Folkert W, Guo, Yiran, van Iperen, Erik PA, Sivapalaratnam, Suthesh, Tragante, Vinicius, Lanktree, Matthew B, Lange, Leslie A, Almoguera, Berta, Appelman, Yolande E, Barnard, John, Baumert, Jens, Beitelshees, Amber L, Bhangale, Tushar R, Chen, Yii-Der Ida, Gaunt, Tom R, Gong, Yan, Hopewell, Jemma C, Johnson, Toby, Kleber, Marcus E, Langaee, Taimour Y, Li, Mingyao, Li, Yun R, Liu, Kiang, McDonough, Caitrin W, Meijs, Matthijs FL, Middelberg, Rita PS, Musunuru, Kiran, Nelson, Christopher P, O’Connell, Jeffery R, Padmanabhan, Sandosh, Pankow, James S, Pankratz, Nathan, Rafelt, Suzanne, Rajagopalan, Ramakrishnan, Romaine, Simon PR, Schork, Nicholas J, Shaffer, Jonathan, Shen, Haiqing, Smith, Erin N, Tischfield, Sam E, van der Most, Peter J, van Vliet-Ostaptchouk, Jana V, Verweij, Niek, Volcik, Kelly A, Zhang, Li, Bailey, Kent R, Bailey, Kristian M, Bauer, Florianne, Boer, Jolanda MA, Braund, Peter S, Burt, Amber, Burton, Paul R, Buxbaum, Sarah G, Chen, Wei, Cooper-DeHoff, Rhonda M, Cupples, L Adrienne, deJong, Jonas S, Delles, Christian, Duggan, David, Fornage, Myriam, Furlong, Clement E, Glazer, Nicole, Gums, John G, Hastie, Claire, Holmes, Michael V, Illig, Thomas, Kirkland, Susan A, Kivimaki, Mika, Klein, Ronald, Klein, Barbara E, Kooperberg, Charles, Kottke-Marchant, Kandice, Kumari, Meena, LaCroix, Andrea Z, Mallela, Laya, Murugesan, Gurunathan, Ordovas, Jose, Ouwehand, Willem H, Post, Wendy S, Saxena, Richa, Scharnagl, Hubert, Schreiner, Pamela J, Shah, Tina, Shields, Denis C, Shimbo, Daichi, Srinivasan, Sathanur R, Stolk, Ronald P, Swerdlow, Daniel I, Taylor, Herman A, Topol, Eric J, Toskala, Elina, van Pelt, Joost L, van Setten, Jessica, Yusuf, Salim, Whittaker, John C, Zwinderman, AH, Study, LifeLines Cohort, Anand, Sonia S, Balmforth, Anthony J, and Berenson, Gerald S

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Human Genome, Cardiovascular, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Cholesterol, HDL, Cholesterol, LDL, Female, Genome-Wide Association Study, Genotype, Humans, Lipids, Male, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Factors, Triglycerides, White People, LifeLines Cohort Study, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.

Published
2012

37. Prediction of Cardiometabolic Health Through Changes in Plasma Proteins With Intentional Weight Loss in the DiRECT and DIADEM-I Randomized Clinical Trials of Type 2 Diabetes Remission

Author

Sattar, Naveed, primary, Taheri, Shahrad, additional, Astling, David P., additional, Chadwick, Jessica, additional, Hinterberg, Michael A., additional, Holmes, Michael V., additional, Troth, Emma V., additional, Welsh, Paul, additional, Zaghloul, Hadeel, additional, Chagoury, Odette, additional, Lean, Mike, additional, Taylor, Roy, additional, and Williams, Steve, additional

Published
2023
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38. PCSK9genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations

Author

Holmes, Michael V, primary, Kartsonaki, Christiana, additional, Boxall, Ruth, additional, Lin, Kuang, additional, Reeve, Nicola, additional, Yu, Canqing, additional, Lv, Jun, additional, Bennett, Derrick A, additional, Hill, Michael R, additional, Yang, Ling, additional, Chen, Yiping, additional, Du, Huaidong, additional, Turnbull, Iain, additional, Collins, Rory, additional, Clarke, Robert J, additional, Tobin, Martin D, additional, Li, Liming, additional, Millwood, Iona Y, additional, Chen, Zhengming, additional, and Walters, Robin G, additional

Published
2023
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39. Guidelines for performing Mendelian randomization investigations: update for summer 2023

Author

Burgess, Stephen, primary, Davey Smith, George, additional, Davies, Neil M., additional, Dudbridge, Frank, additional, Gill, Dipender, additional, Glymour, M. Maria, additional, Hartwig, Fernando P., additional, Kutalik, Zoltán, additional, Holmes, Michael V., additional, Minelli, Cosetta, additional, Morrison, Jean V., additional, Pan, Wei, additional, Relton, Caroline L., additional, and Theodoratou, Evropi, additional

Published
2023
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40. Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and its Risk Factors: Evidence From a Genome‐Wide Association Meta‐Analysis Followed by Mendelian Randomization

Author

Zheng, Jie, primary, Wheeler, Eleanor, additional, Pietzner, Maik, additional, Andlauer, Till F. M., additional, Yau, Michelle S., additional, Hartley, April E., additional, Brumpton, Ben Michael, additional, Rasheed, Humaira, additional, Kemp, John P., additional, Frysz, Monika, additional, Robinson, Jamie, additional, Reppe, Sjur, additional, Prijatelj, Vid, additional, Gautvik, Kaare M., additional, Falk, Louise, additional, Maerz, Winfried, additional, Gergei, Ingrid, additional, Peyser, Patricia A., additional, Kavousi, Maryam, additional, de Vries, Paul S., additional, Miller, Clint L., additional, Bos, Maxime, additional, van der Laan, Sander W., additional, Malhotra, Rajeev, additional, Herrmann, Markus, additional, Scharnagl, Hubert, additional, Kleber, Marcus, additional, Dedoussis, George, additional, Zeggini, Eleftheria, additional, Nethander, Maria, additional, Ohlsson, Claes, additional, Lorentzon, Mattias, additional, Wareham, Nick, additional, Langenberg, Claudia, additional, Holmes, Michael V., additional, Davey Smith, George, additional, and Tobias, Jonathan H., additional

Published
2023
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42. Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Author

Zewinger, Stephen, Kleber, Marcus E, Tragante, Vinicius, McCubrey, Raymond O, Schmidt, Amand F, Direk, Kenan, Laufs, Ulrich, Werner, Christian, Koenig, Wolfgang, Rothenbacher, Dietrich, Mons, Ute, Breitling, Lutz P, Brenner, Herrmann, Jennings, Richard T, Petrakis, Ioannis, Triem, Sarah, Klug, Mira, Filips, Alexandra, Blankenberg, Stefan, Waldeyer, Christoph, Sinning, Christoph, Schnabel, Renate B, Lackner, Karl J, Vlachopoulou, Efthymia, Nygård, Ottar, Svingen, Gard Frodahl Tveitevåg, Pedersen, Eva Ringdal, Tell, Grethe S, Sinisalo, Juha, Nieminen, Markku S, Laaksonen, Reijo, Trompet, Stella, Smit, Roelof A J, Sattar, Naveed, Jukema, J Wouter, Groesdonk, Heinrich V, Delgado, Graciela, Stojakovic, Tatjana, Pilbrow, Anna P, Cameron, Vicky A, Richards, A Mark, Doughty, Robert N, Gong, Yan, Cooper-DeHoff, Rhonda, Johnson, Julie, Scholz, Markus, Beutner, Frank, Thiery, Joachim, Smith, J Gustav, Vilmundarson, Ragnar O, McPherson, Ruth, Stewart, Alexandre F R, Cresci, Sharon, Lenzini, Petra A, Spertus, John A, Olivieri, Oliviero, Girelli, Domenico, Martinelli, Nicola I, Leiherer, Andreas, Saely, Christoph H, Drexel, Heinz, Mündlein, Axel, Braund, Peter S, Nelson, Christopher P, Samani, Nilesh J, Kofink, Daniel, Hoefer, Imo E, Pasterkamp, Gerard, Quyyumi, Arshed A, Ko, Yi-An, Hartiala, Jaana A, Allayee, Hooman, Tang, W H Wilson, Hazen, Stanley L, Eriksson, Niclas, Held, Claes, Hagström, Emil, Wallentin, Lars, Åkerblom, Axel, Siegbahn, Agneta, Karp, Igor, Labos, Christopher, Pilote, Louise, Engert, James C, Brophy, James M, Thanassoulis, George, Bogaty, Peter, Szczeklik, Wojciech, Kaczor, Marcin, Sanak, Marek, Virani, Salim S, Ballantyne, Christie M, Lee, Vei-Vei, Boerwinkle, Eric, Holmes, Michael V, Horne, Benjamin D, Hingorani, Aroon, Asselbergs, Folkert W, Patel, Riyaz S, Krämer, Bernhard K, Scharnagl, Hubert, Fliser, Danilo, März, Winfried, and Speer, Thimoteus

Published
2017
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43. 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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45. Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data

Author

Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo-Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W.H., van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R, Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-van der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., and Patel, Riyaz S.

Published
2020
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47. Body muscle gain and markers of cardiovascular disease susceptibility in young adulthood: A cohort study

Author

Bell, Joshua A., Wade, Kaitlin H., O'Keeffe, Linda M., Carslake, David, Vincent, Emma E., Holmes, Michael V., Timpson, Nicholas J., and Davey Smith, George

Subjects
Young adults -- Health aspects -- Physiological aspects, Grip strength -- Health aspects, Body composition -- Health aspects, Cardiovascular diseases -- Risk factors, Muscles -- Health aspects -- Physiological aspects, Biological sciences
Abstract

Background The potential benefits of gaining body muscle for cardiovascular disease (CVD) susceptibility, and how these compare with the potential harms of gaining body fat, are unknown. We compared associations of early life changes in body lean mass and handgrip strength versus body fat mass with atherogenic traits measured in young adulthood. Methods and findings Data were from 3,227 offspring of the Avon Longitudinal Study of Parents and Children (39% male; recruited in 1991-1992). Limb lean and total fat mass indices (kg/m.sup.2) were measured using dual-energy X-ray absorptiometry scans performed at age 10, 13, 18, and 25 y (across clinics occurring from 2001-2003 to 2015-2017). Handgrip strength was measured at 12 and 25 y, expressed as maximum grip (kg or lb/in.sup.2) and relative grip (maximum grip/weight in kilograms). Linear regression models were used to examine associations of change in standardised measures of these exposures across different stages of body development with 228 cardiometabolic traits measured at age 25 y including blood pressure, fasting insulin, and metabolomics-derived apolipoprotein B lipids. SD-unit gain in limb lean mass index from 10 to 25 y was positively associated with atherogenic traits including very-low-density lipoprotein (VLDL) triglycerides. This pattern was limited to lean gain in legs, whereas lean gain in arms was inversely associated with traits including VLDL triglycerides, insulin, and glycoprotein acetyls, and was also positively associated with creatinine (a muscle product and positive control). Furthermore, this pattern for arm lean mass index was specific to SD-unit gains occurring between 13 and 18 y, e.g., -0.13 SD (95% CI -0.22, -0.04) for VLDL triglycerides. Changes in maximum and relative grip from 12 to 25 y were both positively associated with creatinine, but only change in relative grip was also inversely associated with atherogenic traits, e.g., -0.12 SD (95% CI -0.18, -0.06) for VLDL triglycerides per SD-unit gain. Change in fat mass index from 10 to 25 y was more strongly associated with atherogenic traits including VLDL triglycerides, at 0.45 SD (95% CI 0.39, 0.52); these estimates were directionally consistent across sub-periods, with larger effect sizes with more recent gains. Associations of lean, grip, and fat measures with traits were more pronounced among males. Study limitations include potential residual confounding of observational estimates, including by ectopic fat within muscle, and the absence of grip measures in adolescence for estimates of grip change over sub-periods. Conclusions In this study, we found that muscle strengthening, as indicated by grip strength gain, was weakly associated with lower atherogenic trait levels in young adulthood, at a smaller magnitude than unfavourable associations of fat mass gain. Associations of muscle mass gain with such traits appear to be smaller and limited to gains occurring in adolescence. These results suggest that body muscle is less robustly associated with markers of CVD susceptibility than body fat and may therefore be a lower-priority intervention target., Author(s): Joshua A. Bell 1,2,*, Kaitlin H. Wade 1,2, Linda M. O'Keeffe 1,2,3, David Carslake 1,2, Emma E. Vincent 1,2,4, Michael V. Holmes 1,2,5,6,7, Nicholas J. Timpson 1,2, George Davey [...]

Published
2021
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48. Systematic disease-agnostic identification of therapeutically actionable targets using the genetics of human plasma proteins

Author

Karim, Mohd Anisul, primary, Ariano, Bruno, additional, Schwartzentruber, Jeremy, additional, Roldan-Romero, Juan Maria, additional, Mountjoy, Edward, additional, Hayhurst, James, additional, Buniello, Annalisa, additional, Mohammed, Elmutaz Shaikho Elhaj, additional, Carmona, Miguel, additional, Holmes, Michael V, additional, Robins, Chloe, additional, Surendran, Praveen, additional, Haddad, Stephen, additional, Scott, Robert A, additional, Leach, Andrew R., additional, Ochoa, David, additional, Maranville, Joseph, additional, McDonagh, Ellen M., additional, Dunham, Ian, additional, and Ghoussaini, Maya, additional

Published
2023
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50. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer : a collaborative analysis of 20 prospective studies and Mendelian randomization analysis

Author

Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael, V, Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, MacInnis, Robert J., Mannisto, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael, V, Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, MacInnis, Robert J., Mannisto, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., and Travis, Ruth C.

Abstract

Background Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.

Published
2023
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