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208. The power of genetic diversity in genome-wide association studies of lipids

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Graham, Sarah E, Clarke, Shoa L, Wu, Kuan-Han H, Kanoni, Stavroula, Zajac, Greg JM, 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, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul RHJ, 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 WJ, 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 LR, 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, Chasman, Daniel I., 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, Koistinen, Heikki A, Chandak, Giriraj R, Yajnik, Chittaranjan S, Mercader, Josep M, Tusie-Luna, Teresa, Aguilar-Salinas, Carlos, 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 NA, 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, Hart, Leen M t, Elders, Petra JM, Rader, Daniel J, 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 ALM, 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 KE, Boomsma, Dorret I, de Geus, Eco JC, 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, Tsao, Phil 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, Willer, Cristen J, VA Million Veteran Program, Global Lipids Genetics Consortium, Internal Medicine, Epidemiology, Radiology & Nuclear Medicine, Graham, S. E., Clarke, S. L., Wu, K. -H. H., Kanoni, S., Zajac, G. J. M., Ramdas, S., Surakka, I., Ntalla, I., Vedantam, S., Winkler, T. W., Locke, A. E., Marouli, E., Hwang, M. Y., Han, S., Narita, A., Choudhury, A., Bentley, A. R., Ekoru, K., Verma, A., Trivedi, B., Martin, H. C., Hunt, K. A., Hui, Q., Klarin, D., Zhu, X., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D. F., Holm, H., Olafsson, I., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B. M., Rasheed, H., Ruotsalainen, S. E., Havulinna, A. S., Veturi, Y., Feng, Q. P., Rosenthal, E. A., Lingren, T., Pacheco, J. A., Pendergrass, S. A., Haessler, J., Giulianini, F., Bradford, Y., Miller, J. E., Campbell, A., Lin, K., Millwood, I. Y., Hindy, G., Rasheed, A., Faul, J. D., Zhao, W., Weir, D. R., Turman, C., Huang, H., Graff, M., Mahajan, A., Brown, M. R., Zhang, W., Yu, K., Schmidt, E. M., Pandit, A., Gustafsson, S., Yin, X., Luan, J., Zhao, J. -H., Matsuda, F., Jang, H. -M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J. J., Willemsen, G., Wood, A. R., Ji, Y., Gao, Z., Haworth, S., Mitchell, R. E., Chai, J. F., Aadahl, M., Yao, J., Manichaikul, A., Warren, H. R., Ramirez, J., Bork-Jensen, J., Karhus, L. L., Goel, A., Sabater-Lleal, M., Noordam, R., Sidore, C., Fiorillo, E., Mcdaid, A. F., Marques-Vidal, P., Wielscher, M., Trompet, S., Sattar, N., Mollehave, L. T., Thuesen, B. H., Munz, M., Zeng, L., Huang, J., Yang, B., Poveda, A., Kurbasic, A., Lamina, C., Forer, L., Scholz, M., Galesloot, T. E., Bradfield, J. P., Daw, E. W., Zmuda, J. M., Mitchell, J. S., Fuchsberger, C., Christensen, H., Brody, J. A., Feitosa, M. F., Wojczynski, M. K., Preuss, M., Mangino, M., Christofidou, P., Verweij, N., Benjamins, J. W., Engmann, J., Kember, R. L., Slieker, R. C., Lo, K. S., Zilhao, N. R., Le, P., Kleber, M. E., Delgado, G. E., Huo, S., Ikeda, D. D., Iha, H., Yang, J., Liu, J., Leonard, H. L., Marten, J., Schmidt, B., Arendt, M., Smyth, L. J., Canadas-Garre, M., Wang, C., Nakatochi, M., Wong, A., Hutri-Kahonen, N., Sim, X., Xia, R., Huerta-Chagoya, A., Fernandez-Lopez, J. C., Lyssenko, V., Ahmed, M., Jackson, A. U., Irvin, M. R., Oldmeadow, C., Kim, H. -N., Ryu, S., Timmers, P. R. H. J., Arbeeva, L., Dorajoo, R., Lange, L. A., Chai, X., Prasad, G., Lores-Motta, L., Pauper, M., Long, J., Li, X., Theusch, E., Takeuchi, F., Spracklen, C. N., Loukola, A., Bollepalli, S., Warner, S. C., Wang, Y. X., Wei, W. B., Nutile, T., Ruggiero, D., Sung, Y. J., Hung, Y. -J., Chen, S., Liu, F., Kentistou, K. A., Gorski, M., Brumat, M., Meidtner, K., Bielak, L. F., Smith, J. A., Hebbar, P., Farmaki, A. -E., Hofer, E., Lin, M., Xue, C., Zhang, J., Concas, M. P., Vaccargiu, S., van der Most, P. J., Pitkanen, N., Cade, B. E., Lee, J., van der Laan, S. W., Chitrala, K. N., Weiss, S., Zimmermann, M. E., Lee, J. Y., Choi, H. S., Nethander, M., Freitag-Wolf, S., Southam, L., Rayner, N. W., Wang, C. A., Lin, S. -Y., Wang, J. -S., Couture, C., Lyytikainen, L. -P., Nikus, K., Cuellar-Partida, G., Vestergaard, H., Hildalgo, B., Giannakopoulou, O., Cai, Q., Obura, M. O., van Setten, J., Schwander, K., Terzikhan, N., Shin, J. H., Jackson, R. D., Reiner, A. P., Martin, L. W., Chen, Z., Li, L., Highland, H. M., Young, K. L., Kawaguchi, T., Thiery, J., Bis, J. C., Nadkarni, G. N., Launer, L. J., Li, H., Nalls, M. A., Raitakari, O. T., Ichihara, S., Wild, S. H., Nelson, C. P., Campbell, H., Jager, S., Nabika, T., Al-Mulla, F., Niinikoski, H., Braund, P. S., Kolcic, I., Kovacs, P., Giardoglou, T., Katsuya, T., Bhatti, K. F., de Kleijn, D., de Borst, G. J., Kim, E. K., Adams, H. H. H., Ikram, M. A., Asselbergs, F. W., Kraaijeveld, A. O., Beulens, J. W. J., Shu, X. -O., Rallidis, L. S., Pedersen, O., Hansen, T., Mitchell, P., Hewitt, A. W., Kahonen, M., Perusse, L., Bouchard, C., Tonjes, A., Chen, Y. -D. I., Pennell, C. E., Mori, T. A., Lieb, W., Franke, A., Ohlsson, C., Mellstrom, D., Cho, Y. S., Lee, H., Yuan, J. -M., Koh, W. -P., Rhee, S. Y., Woo, J. -T., Heid, I. M., Stark, K. J., Volzke, H., Homuth, G., Evans, M. K., Zonderman, A. B., Polasek, O., Pasterkamp, G., Hoefer, I. E., Redline, S., Pahkala, K., Oldehinkel, A. J., Snieder, H., Biino, G., Schmidt, R., Schmidt, H., Chen, Y. E., Bandinelli, S., Dedoussis, G., Thanaraj, T. A., Kardia, S. L. R., Kato, N., Schulze, M. B., Girotto, G., Jung, B., Boger, C. A., Joshi, P. K., Bennett, D. A., De Jager, P. L., Lu, X., Mamakou, V., Brown, M., Caulfield, M. J., Munroe, P. B., Guo, X., Ciullo, M., Jonas, J. B., Samani, N. J., Kaprio, J., Pajukanta, P., Adair, L. S., Bechayda, S. A., de Silva, H. J., Wickremasinghe, A. R., Krauss, R. M., Wu, J. -Y., Zheng, W., den Hollander, A. I., Bharadwaj, D., Correa, A., Wilson, J. G., Lind, L., Heng, C. -K., Nelson, A. E., Golightly, Y. M., Wilson, J. F., Penninx, B., Kim, H. -L., Attia, J., Scott, R. J., Rao, D. C., Arnett, D. K., Walker, M., Koistinen, H. A., Chandak, G. R., Yajnik, C. S., Mercader, J. M., Tusie-Luna, T., Aguilar-Salinas, C. A., Villalpando, C. G., Orozco, L., Fornage, M., Tai, E. S., van Dam, R. M., Lehtimaki, T., Chaturvedi, N., Yokota, M., Reilly, D. F., Mcknight, A. J., Kee, F., Jockel, K. -H., Mccarthy, M. I., Palmer, C. N. A., Vitart, V., Hayward, C., Simonsick, E., van Duijn, C. M., Lu, F., Qu, J., Hishigaki, H., Lin, X., Marz, W., Parra, E. J., Cruz, M., Gudnason, V., Tardif, J. -C., Lettre, G., 't Hart, L. M., Elders, P. J. M., Damrauer, S. M., Kumari, M., Kivimaki, M., van der Harst, P., Spector, T. D., Loos, R. J. F., Province, M. A., Psaty, B. M., Brandslund, I., Pramstaller, P. P., Christensen, K., Ripatti, S., Widen, E., Hakonarson, H., Grant, S. F. A., Kiemeney, L. A. L. M., de Graaf, J., Loeffler, M., Kronenberg, F., Gu, D., Erdmann, J., Schunkert, H., Franks, P. W., Linneberg, A., Jukema, J. W., Khera, A. V., Mannikko, M., Jarvelin, M. -R., Kutalik, Z., Cucca, F., Mook-Kanamori, D. O., van Dijk, K. W., Watkins, H., Strachan, D. P., Grarup, N., Sever, P., Poulter, N., Rotter, J. I., Dantoft, T. M., Karpe, F., Neville, M. J., Timpson, N. J., Cheng, C. -Y., Wong, T. -Y., Khor, C. C., Sabanayagam, C., Peters, A., Gieger, C., Hattersley, A. T., Pedersen, N. L., Magnusson, P. K. E., Boomsma, D. I., de Geus, E. J. C., Cupples, L. A., van Meurs, J. B. J., Ghanbari, M., Gordon-Larsen, P., Huang, W., Kim, Y. J., Tabara, Y., Wareham, N. J., Langenberg, C., Zeggini, E., Kuusisto, J., Laakso, M., Ingelsson, E., Abecasis, G., Chambers, J. C., Kooner, J. S., de Vries, P. S., Morrison, A. C., North, K. E., Daviglus, M., Kraft, P., Martin, N. G., Whitfield, J. B., Abbas, S., Saleheen, D., Walters, R. G., Holmes, M. V., Black, C., Smith, B. H., Justice, A. E., Baras, A., Buring, J. E., Ridker, P. M., Chasman, D. I., Kooperberg, C., Wei, W. -Q., Jarvik, G. P., Namjou, B., Hayes, M. G., Ritchie, M. D., Jousilahti, P., Salomaa, V., Hveem, K., Asvold, B. O., Kubo, M., Kamatani, Y., Okada, Y., Murakami, Y., Thorsteinsdottir, U., Stefansson, K., Ho, Y. -L., Lynch, J. A., Rader, D. J., Tsao, P. S., Chang, K. -M., Cho, K., O'Donnell, C. J., Gaziano, J. M., Wilson, P., Rotimi, C. N., Hazelhurst, S., Ramsay, M., Trembath, R. C., van Heel, D. A., Tamiya, G., Yamamoto, M., Kim, B. -J., Mohlke, K. L., Frayling, T. M., Hirschhorn, J. N., Kathiresan, S., Boehnke, M., Natarajan, P., Peloso, G. M., Brown, C. D., Morris, A. P., Assimes, T. L., Deloukas, P., Sun, Y. V., Willer, C. J., Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, AMS - Ageing & Vitality, and AMS - Sports

Subjects
blood lipid level, Multifactorial Inheritance, GWAS, blood lipid levels, cardiovascular disease, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Medizin, LOCI, ANCESTRY, VARIANTS, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Article, Population Groups, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, METAANALYSIS, POLYMORPHISMS, RISK, Multidisciplinary, Cardiovascular Diseases, Genome-Wide Association Study, Cardiovascular Diseases/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study/methods, Polymorphism, Single Nucleotide/genetics, CHOLESTEROL, Human Genetics, INDIVIDUALS, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], DISCOVERY, LOW-FREQUENCY, Delivery of Health Care
Abstract

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use 1 . Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels 2 , heart disease remains the leading cause of death worldwide 3 . Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS 4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns 24 . Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine 25 , we anticipate that increased diversity of participants will lead to more accurate and equitable 26 application of polygenic scores in clinical practice.

Published
2021
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209. Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4

Author

Grosche, Sarah, Marenholz, Ingo, Esparza-gordillo, Jorge, Arnau-soler, Aleix, Pairo-castineira, Erola, Rüschendorf, Franz, Ahluwalia, Tarunveer S., Almqvist, Catarina, Arnold, Andreas, Baurecht, Hansjörg, Bisgaard, Hans, Bønnelykke, Klaus, Brown, Sara J., Bustamante, Mariona, Curtin, John A., Dharmage, Shyamali C., Esplugues, Ana, Falchi, Mario, Fernandez-orth, Dietmar, Ferreira, Manuel A. R., Franke, Andre, Gerdes, Sascha, Gieger, Christian, Hakonarson, Hakon, Holt, Patrick G., Homuth, Georg, Hubner, Norbert, Hysi, Pirro G., Jarvelin, Marjo-riitta, Karlsson, Robert, Koppelman, Gerard H., Lau, Susanne, Lutz, Manuel, Magnusson, Patrik K. E., Marks, Guy B., Müller-nurasyid, Martina, Nöthen, Markus M., Paternoster, Lavinia, Pennell, Craig E., Peters, Annette, Rawlik, Konrad, Robertson, Colin F., Rodriguez, Elke, Sebert, Sylvain, Simpson, Angela, Sleiman, Patrick M. A., Standl, Marie, Stölzl, Dora, Strauch, Konstantin, Szwajda, Agnieszka, Tenesa, Albert, Ullemar, Vilhelmina, Visconti, Alessia, Vonk, Judith M., Wang, Carol A., Weidinger, Stephan, Wielscher, Matthias, Worth, Catherine L., Xu, Chen-jian, and Lee, Young-ae

Abstract

Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.

Published
2021
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210. Genome-wide association analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Author

Eising, Else, Mirza-Schreiber, Nazanin, de Zeeuw, Eveline L, Wang, Carol A, Truong, Dongnhu T, Allegrini, Andrea G, Shapland, Chin Yang, Zhu, Gu, Wigg, Karen G, Gerritse, Margot, Molz, Barbara, Alagöz, Gökberk, Gialluisi, Alessandro, Abbondanza, Filippo, Rimfeld, Kaili, van Donkelaar, Marjolein, Liao, Zhijie, Jansen, Philip R, Andlauer, Till F M, Bates, Timothy C, Bernard, Manon, Blokland, Kirsten, Børglum, Anders D, Bourgeron, Thomas, Brandeis, Daniel, Ceroni, Fabiola, Dale, Philip S, Landerl, Karin, Lyytinen, Heikki, de Jong, Peter F, et al, and University of Zurich

Subjects
10076 Center for Integrative Human Physiology, 610 Medicine & health, 10058 Department of Child and Adolescent Psychiatry, 10064 Neuroscience Center Zurich
Published
2021

213. Genome-wide association analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Author

Eising, Else, primary, Mirza-Schreiber, Nazanin, additional, de Zeeuw, Eveline L., additional, Wang, Carol A., additional, Truong, Dongnhu T., additional, Allegrini, Andrea G., additional, Shapland, Chin Yang, additional, Zhu, Gu, additional, Wigg, Karen G., additional, Gerritse, Margot, additional, Molz, Barbara, additional, Alagöz, Gökberk, additional, Gialluisi, Alessandro, additional, Abbondanza, Filippo, additional, Rimfeld, Kaili, additional, van Donkelaar, Marjolein, additional, Liao, Zhijie, additional, Jansen, Philip R., additional, Andlauer, Till F. M., additional, Bates, Timothy C., additional, Bernard, Manon, additional, Blokland, Kirsten, additional, Børglum, Anders D., additional, Bourgeron, Thomas, additional, Brandeis, Daniel, additional, Ceroni, Fabiola, additional, Dale, Philip S., additional, Landerl, Karin, additional, Lyytinen, Heikki, additional, de Jong, Peter F., additional, DeFries, John C., additional, Demontis, Ditte, additional, Feng, Yu, additional, Gordon, Scott D., additional, Guger, Sharon L., additional, Hayiou-Thomas, Marianna E., additional, Hernández-Cabrera, Juan A., additional, Hottenga, Jouke-Jan, additional, Hulme, Charles, additional, Kerr, Elizabeth N., additional, Koomar, Tanner, additional, Lovett, Maureen W., additional, Martin, Nicholas G., additional, Martinelli, Angela, additional, Maurer, Urs, additional, Michaelson, Jacob J., additional, Moll, Kristina, additional, Monaco, Anthony P., additional, Morgan, Angela T., additional, Nöthen, Markus M., additional, Pausova, Zdenka, additional, Pennell, Craig E., additional, Pennington, Bruce F, additional, Price, Kaitlyn M., additional, Rajagopal, Veera M., additional, Ramus, Frank, additional, Richer, Louis, additional, Simpson, Nuala H., additional, Smith, Shelley, additional, Snowling, Margaret J., additional, Stein, John, additional, Strug, Lisa J., additional, Talcott, Joel B., additional, Tiemeier, Henning, additional, van de Schroeff, Marc M.P., additional, Verhoef, Ellen, additional, Watkins, Kate E., additional, Wilkinson, Margaret, additional, Wright, Margaret J., additional, Barr, Cathy L., additional, Boomsma, Dorret I., additional, Carreiras, Manuel, additional, Franken, Marie-Christine J., additional, Gruen, Jeffrey R., additional, Luciano, Michelle, additional, Müller-Myhsok, Bertram, additional, Newbury, Dianne F., additional, Olson, Richard K., additional, Paracchini, Silvia, additional, Paus, Tomas, additional, Plomin, Robert, additional, Schulte-Körne, Gerd, additional, Reilly, Sheena, additional, Tomblin, J. Bruce, additional, van Bergen, Elsje, additional, Whitehouse, Andrew J.O., additional, Willcutt, Erik G., additional, Pourcain, Beate St, additional, Francks, Clyde, additional, and Fisher, Simon E., additional

Published
2021
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214. Genome Wide Association Metanalysis Of Skull Bone Mineral Density Identifies Loci Relevant For Osteoporosis And Craniosynostosis

Author

Medina-Gomez, Carolina, primary, Mullin, Benjamin H., additional, Chesi, Alessandra, additional, Prijatelj, Vid, additional, Kemp, John P., additional, Shochat-Carvalho, Chen, additional, Trajanoska, Katerina, additional, Wang, Carol, additional, Joro, Raimo, additional, Evans, Tavia E., additional, Schraut, Katharina E., additional, Li-Gao, Ruifang, additional, Ahluwalia, Tarunveer S., additional, Zillikens, M. Carola, additional, Zhu, Kun, additional, Mook-Kanamori, Dennis O., additional, Evans, Daniel S., additional, Nethander, Maria, additional, Knol, Maria J., additional, Thorleifsson, Gudmar, additional, Prokic, Ivana, additional, Zemel, Babette, additional, Broer, Linda, additional, van Schoor, Natasja, additional, Reppe, Sjur, additional, Pawlak, Mikolaj A., additional, Ralston, Stuart H., additional, van der Velde, Nathalie, additional, Lorentzon, Mattias, additional, Stefansson, Kari, additional, Adams, Hieab H.H., additional, Wilson, Scott G., additional, Ikram, M. Arfan, additional, Walsh, John P., additional, Lakka, Timo A., additional, Gautvik, Kaare M., additional, Wilson, James F, additional, Orwoll, Eric S., additional, van Duijn, Cornelia M., additional, Bønnelykke, Klaus, additional, Uitterlinden, Andre G., additional, Stykársdóttir, Unnur, additional, Spector, Timothy D., additional, Tobias, Jonathan H, additional, Ohlsson, Claes, additional, Felix, Janine F., additional, Bisgaard, Hans, additional, Grant, Struan F.A., additional, Richards, J. Brent, additional, Evans, David M., additional, van der Eerden, Bram, additional, van de Peppel, Jeroen, additional, Ackert-Bicknell, Cheryl, additional, Karasik, David, additional, Kague, Erika, additional, and Rivadeneira, Fernando, additional

Published
2021
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215. Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3

Author

Nolan, James, primary, Campbell, Purdey J, additional, Brown, Suzanne J, additional, Zhu, Gu, additional, Gordon, Scott, additional, Lim, Ee Mun, additional, Joseph, John, additional, Cross, Simone M, additional, Panicker, Vijay, additional, Medland, Sarah E, additional, Melton, Phillip E, additional, Beilin, Lawrence J, additional, Mori, Trevor A, additional, Mullin, Benjamin H, additional, Pennell, Craig E, additional, Wang, Carol A, additional, Dudbridge, Frank, additional, Walsh, John P, additional, Martin, Nicholas G, additional, and Wilson, Scott G, additional

Published
2021
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217. W58. GENOME-WIDE ASSOCIATION META-ANALYSIS OF EXPRESSIVE AND RECEPTIVE VOCABULARY FROM INFANCY TO EARLY CHILDHOOD: LINKS TO COGNITIVE OUTCOMES AND BEHAVIORAL TRAITS IN LATER LIFE

Author

Verhoef, Ellen, primary, Ahluwalia, Tarunveer, additional, Jansen, Philip, additional, Lange, Katherine, additional, Allegrini, Andrea, additional, Wang, Carol, additional, Symeonides, Christos, additional, Morgan, Angela, additional, Fisher, Simon E., additional, and Pourcain, Beate St, additional

Published
2021
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219. Genetic effects on the timing of parturition and links to fetal birth weight

Author

Solé-Navais, Pol, Flatley, Christopher, Steinthorsdottir, Valgerdur, Vaudel, Marc, Juodakis, Julius, Chen, Jing, Laisk, Triin, LaBella, Abigail L., Westergaard, David, Bacelis, Jonas, Brumpton, Ben, Skotte, Line, Borges, Maria C., Helgeland, Øyvind, Mahajan, Anubha, Wielscher, Matthias, Lin, Frederick, Briggs, Catherine, Wang, Carol A., Moen, Gunn-Helen, Beaumont, Robin N., Bradfield, Jonathan P., Abraham, Abin, Thorleifsson, Gudmar, Gabrielsen, Maiken E., Ostrowski, Sisse R., Modzelewska, Dominika, Nohr, Ellen A., Hypponen, Elina, Srivastava, Amit, Talbot, Octavious, Allard, Catherine, Williams, Scott M., Menon, Ramkumar, Shields, Beverley M., Sveinbjornsson, Gardar, Xu, Huan, Melbye, Mads, Lowe, William, Bouchard, Luigi, Oken, Emily, Pedersen, Ole B., Gudbjartsson, Daniel F., Erikstrup, Christian, Sørensen, Erik, Lie, Rolv T., Teramo, Kari, Hallman, Mikko, Juliusdottir, Thorhildur, Hakonarson, Hakon, Ullum, Henrik, Hattersley, Andrew T., Sletner, Line, Merialdi, Mario, Rifas-Shiman, Sheryl L., Steingrimsdottir, Thora, Scholtens, Denise, Power, Christine, West, Jane, Nyegaard, Mette, Capra, John A., Skogholt, Anne H., Magnus, Per, Andreassen, Ole A., Thorsteinsdottir, Unnur, Grant, Struan F. A., Qvigstad, Elisabeth, Pennell, Craig E., Hivert, Marie-France, Hayes, Geoffrey M., Jarvelin, Marjo-Riitta, McCarthy, Mark I., Lawlor, Deborah A., Nielsen, Henriette S., Mägi, Reedik, Rokas, Antonis, Hveem, Kristian, Stefansson, Kari, Feenstra, Bjarke, Njolstad, Pål, Muglia, Louis J., Freathy, Rachel M., Johansson, Stefan, Zhang, Ge, and Jacobsson, Bo

Abstract

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n= 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed seven associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n= 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.

Published
2023
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223. Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations

Author

Haslam, Danielle E., primary, Peloso, Gina M., additional, Guirette, Melanie, additional, Imamura, Fumiaki, additional, Bartz, Traci M., additional, Pitsillides, Achilleas N., additional, Wang, Carol A., additional, Li-Gao, Ruifang, additional, Westra, Jason M., additional, Pitkänen, Niina, additional, Young, Kristin L., additional, Graff, Mariaelisa, additional, Wood, Alexis C., additional, Braun, Kim V.E., additional, Luan, Jian’an, additional, Kähönen, Mika, additional, Kiefte-de Jong, Jessica C., additional, Ghanbari, Mohsen, additional, Tintle, Nathan, additional, Lemaitre, Rozenn N., additional, Mook-Kanamori, Dennis O., additional, North, Kari, additional, Helminen, Mika, additional, Mossavar-Rahmani, Yasmin, additional, Snetselaar, Linda, additional, Martin, Lisa W., additional, Viikari, Jorma S., additional, Oddy, Wendy H., additional, Pennell, Craig E., additional, Rosendall, Frits R., additional, Ikram, M. Arfan, additional, Uitterlinden, Andre G, additional, Psaty, Bruce M., additional, Mozaffarian, Dariush, additional, Rotter, Jerome I., additional, Taylor, Kent D., additional, Lehtimäki, Terho, additional, Raitakari, Olli T., additional, Livingston, Kara A., additional, Voortman, Trudy, additional, Forouhi, Nita G., additional, Wareham, Nick J., additional, de Mutsert, Renée, additional, Rich, Steven S., additional, Manson, JoAnn E., additional, Mora, Samia, additional, Ridker, Paul M., additional, Merino, Jordi, additional, Meigs, James B., additional, Dashti, Hassan S., additional, Chasman, Daniel I., additional, Lichtenstein, Alice H., additional, Smith, Caren E., additional, Dupuis, Josée, additional, Herman, Mark A., additional, and McKeown, Nicola M., additional

Published
2021
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224. Genetic association study of childhood aggression across raters, instruments, and age

Author

Ip, Hill F., primary, van der Laan, Camiel M., additional, Krapohl, Eva M. L., additional, Brikell, Isabell, additional, Sánchez-Mora, Cristina, additional, Nolte, Ilja M., additional, St Pourcain, Beate, additional, Bolhuis, Koen, additional, Palviainen, Teemu, additional, Zafarmand, Hadi, additional, Colodro-Conde, Lucía, additional, Gordon, Scott, additional, Zayats, Tetyana, additional, Aliev, Fazil, additional, Jiang, Chang, additional, Wang, Carol A., additional, Saunders, Gretchen, additional, Karhunen, Ville, additional, Hammerschlag, Anke R., additional, Adkins, Daniel E., additional, Border, Richard, additional, Peterson, Roseann E., additional, Prinz, Joseph A., additional, Thiering, Elisabeth, additional, Seppälä, Ilkka, additional, Vilor-Tejedor, Natàlia, additional, Ahluwalia, Tarunveer S., additional, Day, Felix R., additional, Hottenga, Jouke-Jan, additional, Allegrini, Andrea G., additional, Rimfeld, Kaili, additional, Chen, Qi, additional, Lu, Yi, additional, Martin, Joanna, additional, Soler Artigas, María, additional, Rovira, Paula, additional, Bosch, Rosa, additional, Español, Gemma, additional, Ramos Quiroga, Josep Antoni, additional, Neumann, Alexander, additional, Ensink, Judith, additional, Grasby, Katrina, additional, Morosoli, José J., additional, Tong, Xiaoran, additional, Marrington, Shelby, additional, Middeldorp, Christel, additional, Scott, James G., additional, Vinkhuyzen, Anna, additional, Shabalin, Andrey A., additional, Corley, Robin, additional, Evans, Luke M., additional, Sugden, Karen, additional, Alemany, Silvia, additional, Sass, Lærke, additional, Vinding, Rebecca, additional, Ruth, Kate, additional, Tyrrell, Jess, additional, Davies, Gareth E., additional, Ehli, Erik A., additional, Hagenbeek, Fiona A., additional, De Zeeuw, Eveline, additional, Van Beijsterveldt, Toos C.E.M., additional, Larsson, Henrik, additional, Snieder, Harold, additional, Verhulst, Frank C., additional, Amin, Najaf, additional, Whipp, Alyce M., additional, Korhonen, Tellervo, additional, Vuoksimaa, Eero, additional, Rose, Richard J., additional, Uitterlinden, André G., additional, Heath, Andrew C., additional, Madden, Pamela, additional, Haavik, Jan, additional, Harris, Jennifer R., additional, Helgeland, Øyvind, additional, Johansson, Stefan, additional, Knudsen, Gun Peggy S., additional, Njolstad, Pal Rasmus, additional, Lu, Qing, additional, Rodriguez, Alina, additional, Henders, Anjali K., additional, Mamun, Abdullah, additional, Najman, Jackob M., additional, Brown, Sandy, additional, Hopfer, Christian, additional, Krauter, Kenneth, additional, Reynolds, Chandra, additional, Smolen, Andrew, additional, Stallings, Michael, additional, Wadsworth, Sally, additional, Wall, Tamara L., additional, Silberg, Judy L., additional, Miller, Allison, additional, Keltikangas-Järvinen, Liisa, additional, Hakulinen, Christian, additional, Pulkki-Råback, Laura, additional, Havdahl, Alexandra, additional, Magnus, Per, additional, Raitakari, Olli T., additional, Perry, John R. B., additional, Llop, Sabrina, additional, Lopez-Espinosa, Maria-Jose, additional, Bønnelykke, Klaus, additional, Bisgaard, Hans, additional, Sunyer, Jordi, additional, Lehtimäki, Terho, additional, Arseneault, Louise, additional, Standl, Marie, additional, Heinrich, Joachim, additional, Boden, Joseph, additional, Pearson, John, additional, Horwood, L. John, additional, Kennedy, Martin, additional, Poulton, Richie, additional, Eaves, Lindon J., additional, Maes, Hermine H., additional, Hewitt, John, additional, Copeland, William E., additional, Costello, Elizabeth J., additional, Williams, Gail M., additional, Wray, Naomi, additional, Järvelin, Marjo-Riitta, additional, McGue, Matt, additional, Iacono, William, additional, Caspi, Avshalom, additional, Moffitt, Terrie E., additional, Whitehouse, Andrew, additional, Pennell, Craig E., additional, Klump, Kelly L., additional, Burt, S. Alexandra, additional, Dick, Danielle M., additional, Reichborn-Kjennerud, Ted, additional, Martin, Nicholas G., additional, Medland, Sarah E., additional, Vrijkotte, Tanja, additional, Kaprio, Jaakko, additional, Tiemeier, Henning, additional, Davey Smith, George, additional, Hartman, Catharina A., additional, Oldehinkel, Albertine J., additional, Casas, Miquel, additional, Ribasés, Marta, additional, Lichtenstein, Paul, additional, Lundström, Sebastian, additional, Plomin, Robert, additional, Bartels, Meike, additional, Nivard, Michel G., additional, and Boomsma, Dorret I., additional

Published
2021
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227. Publisher Correction: Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author

Kentistou, Katherine A., Kaisinger, Lena R., Stankovic, Stasa, Vaudel, Marc, Mendes de Oliveira, Edson, Messina, Andrea, Walters, Robin G., Liu, Xiaoxi, Busch, Alexander S., Helgason, Hannes, Thompson, Deborah J., Santoni, Federico, Petricek, Konstantin M., Zouaghi, Yassine, Huang-Doran, Isabel, Gudbjartsson, Daniel F., Bratland, Eirik, Lin, Kuang, Gardner, Eugene J., Zhao, Yajie, Jia, Raina Y., Terao, Chikashi, Riggan, Marjorie J., Bolla, Manjeet K., Yazdanpanah, Mojgan, Yazdanpanah, Nahid, Bradfield, Jonathan P., Broer, Linda, Campbell, Archie, Chasman, Daniel I., Cousminer, Diana L., Franceschini, Nora, Franke, Lude H., Girotto, Giorgia, He, Chunyan, Järvelin, Marjo-Riitta, Joshi, Peter K., Kamatani, Yoichiro, Karlsson, Robert, Luan, Jian’an, Lunetta, Kathryn L., Mägi, Reedik, Mangino, Massimo, Medland, Sarah E., Meisinger, Christa, Noordam, Raymond, Nutile, Teresa, Concas, Maria Pina, Polašek, Ozren, Porcu, Eleonora, Ring, Susan M., Sala, Cinzia, Smith, Albert V., Tanaka, Toshiko, van der Most, Peter J., Vitart, Veronique, Wang, Carol A., Willemsen, Gonneke, Zygmunt, Marek, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Auer, Paul L., Barnes, Catriona L. K., Beckmann, Matthias W., Berrington de Gonzalez, Amy, Bogdanova, Natalia V., Bojesen, Stig E., Brenner, Hermann, Buring, Julie E., Canzian, Federico, Chang-Claude, Jenny, Couch, Fergus J., Cox, Angela, Crisponi, Laura, Czene, Kamila, Daly, Mary B., Demerath, Ellen W., Dennis, Joe, Devilee, Peter, De Vivo, Immaculata, Dörk, Thilo, Dunning, Alison M., Dwek, Miriam, Eriksson, Johan G., Fasching, Peter A., Fernandez-Rhodes, Lindsay, Ferreli, Liana, Fletcher, Olivia, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A., González-Neira, Anna, Grallert, Harald, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hakonarson, Hakon, Hart, Roger J., Hickey, Martha, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Hottenga, Jouke-Jan, Hu, Frank B., Huebner, Hanna, Hunter, David J., Jernström, Helena, John, Esther M., Karasik, David, Khusnutdinova, Elza K., Kristensen, Vessela N., Lacey, James V., Lambrechts, Diether, Launer, Lenore J., Lind, Penelope A., Lindblom, Annika, Magnusson, Patrik K. E., Mannermaa, Arto, McCarthy, Mark I., Meitinger, Thomas, Menni, Cristina, Michailidou, Kyriaki, Millwood, Iona Y., Milne, Roger L., Montgomery, Grant W., Nevanlinna, Heli, Nolte, Ilja M., Nyholt, Dale R., Obi, Nadia, O’Brien, Katie M., Offit, Kenneth, Oldehinkel, Albertine J., Ostrowski, Sisse R., Palotie, Aarno, Pedersen, Ole B., Peters, Annette, Pianigiani, Giulia, Plaseska-Karanfilska, Dijana, Pouta, Anneli, Pozarickij, Alfred, Radice, Paolo, Rennert, Gad, Rosendaal, Frits R., Ruggiero, Daniela, Saloustros, Emmanouil, Sandler, Dale P., Schipf, Sabine, Schmidt, Carsten O., Schmidt, Marjanka K., Small, Kerrin, Spedicati, Beatrice, Stampfer, Meir, Stone, Jennifer, Tamimi, Rulla M., Teras, Lauren R., Tikkanen, Emmi, Turman, Constance, Vachon, Celine M., Wang, Qin, Winqvist, Robert, Wolk, Alicja, Zemel, Babette S., Zheng, Wei, van Dijk, Ko W., Alizadeh, Behrooz Z., Bandinelli, Stefania, Boerwinkle, Eric, Boomsma, Dorret I., Ciullo, Marina, Chenevix-Trench, Georgia, Cucca, Francesco, Esko, Tõnu, Gieger, Christian, Grant, Struan F. A., Gudnason, Vilmundur, Hayward, Caroline, Kolčić, Ivana, Kraft, Peter, Lawlor, Deborah A., Martin, Nicholas G., Nøhr, Ellen A., Pedersen, Nancy L., Pennell, Craig E., Ridker, Paul M., Robino, Antonietta, Snieder, Harold, Sovio, Ulla, Spector, Tim D., Stöckl, Doris, Sudlow, Cathie, Timpson, Nic J., Toniolo, Daniela, Uitterlinden, André, Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Widen, Elisabeth, Wilson, James F., Pharoah, Paul D. P., Li, Liming, Easton, Douglas F., Njølstad, Pål R., Sulem, Patrick, Murabito, Joanne M., Murray, Anna, Manousaki, Despoina, Juul, Anders, Erikstrup, Christian, Stefansson, Kari, Horikoshi, Momoko, Chen, Zhengming, Farooqi, I. Sadaf, Pitteloud, Nelly, Johansson, Stefan, Day, Felix R., Perry, John R. B., and Ong, Ken K.

Published
2024
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228. Continuity of Genetic Risk for Aggressive Behavior Across the Life-Course

Author

van der Laan, Camiel M., Morosoli-García, José J., van de Weijer, Steve G.A., Colodro-Conde, Lucía, Ip, Hill F., Krapohl, Eva M.L., Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja M., Pourcain, Beate St, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol A., Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke R., Adkins, Daniel E., Border, Richard, Peterson, Roseann E., Prinz, Joseph A., Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer S., Day, Felix R., Allegrini, Andrea G., Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Artigas, María Soler, Rovira, Paula, Bosch, Rosa, Español, Gemma, Neumann, Alexander, Middeldorp, Christel, Verhulst, Frank C., Amin, Najaf, Uitterlinden, André G., Perry, John R.B., Heinrich, Joachim, Tiemeier, Henning, Bartels, Meike, Hottenga, Jouke Jan, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Internal Medicine, Ophthalmology, Epidemiology, Public Health, Adult Psychiatry, Epidemiology and Data Science, APH - Aging & Later Life, APH - Methodology, AR&D - Amsterdam Reproduction & Development, Graduate School, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, Public and occupational health, APH - Health Behaviors & Chronic Diseases, ACS - Pulmonary hypertension & thrombosis, Biological Psychology, Criminology, APH - Mental Health, APH - Personalized Medicine, Life Course Epidemiology (LCE), Macromolecular Chemistry & New Polymeric Materials, and Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)

Subjects
Adult, medicine.medical_specialty, Multifactorial Inheritance, Adolescent, 0608 Zoology, Development, Young Adult, Life-course, Risk Factors, Polygenic score, Genetics, medicine, ACTION Consortium, Humans, Genetic risk, Child, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Aged, Netherlands, Original Research, Genetics & Heredity, Aggression, Public health, Australia, Aggressive behavior, Middle Aged, Rolling weights, Early life, Health psychology, 1701 Psychology, Life course approach, medicine.symptom, Psychology, 1109 Neurosciences, Demography
Abstract

We test whether genetic influences that explain individual differences in aggression in early life also explain individual differences across the life-course. In two cohorts from The Netherlands (N = 13,471) and Australia (N = 5628), polygenic scores (PGSs) were computed based on a genome-wide meta-analysis of childhood/adolescence aggression. In a novel analytic approach, we ran a mixed effects model for each age (Netherlands: 12–70 years, Australia: 16–73 years), with observations at the focus age weighted as 1, and decaying weights for ages further away. We call this approach a ‘rolling weights’ model. In The Netherlands, the estimated effect of the PGS was relatively similar from age 12 to age 41, and decreased from age 41–70. In Australia, there was a peak in the effect of the PGS around age 40 years. These results are a first indication from a molecular genetics perspective that genetic influences on aggressive behavior that are expressed in childhood continue to play a role later in life. Supplementary Information The online version contains supplementary material available at 10.1007/s10519-021-10076-6.

Published
2021
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229. 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 and Ntalla, Ioanna Vedantam, Sailaja Winkler, Thomas W. Locke, Adam E. Marouli, Eirini Hwang, Mi Yeong Han, Sohee and Narita, Akira Choudhury, Ananyo Bentley, Amy R. Ekoru, Kenneth Verma, Anurag Trivedi, Bhavi Martin, Hilary C. and Hunt, Karen A. Hui, Qin Klarin, Derek Zhu, Xiang and Thorleifsson, Gudmar Helgadottir, Anna Gudbjartsson, Daniel F. and Holm, Hilma Olafsson, Isleifur Akiyama, Masato Sakaue, Saori Terao, Chikashi Kanai, Masahiro Zhou, Wei and Brumpton, Ben M. Rasheed, Humaira Ruotsalainen, Sanni E. and Havulinna, Aki S. Veturi, Yogasudha Feng, QiPing Rosenthal, Elisabeth A. Lingren, Todd Pacheco, Jennifer Allen and Pendergrass, Sarah A. Haessler, Jeffrey Giulianini, Franco and Bradford, Yuki Miller, Jason E. Campbell, Archie Lin, Kuang and Millwood, Iona Y. Hindy, George Rasheed, Asif Faul, Jessica D. Zhao, Wei Weir, David R. Turman, Constance and Huang, Hongyan Graff, Mariaelisa Mahajan, Anubha Brown, Michael R. Zhang, Weihua Yu, Ketian Schmidt, Ellen M. and Pandit, Anita Gustafsson, Stefan Yin, Xianyong Luan, Jian'an and Zhao, Jing-Hua Matsuda, Fumihiko Jang, Hye-Mi Yoon, Kyungheon Medina-Gomez, Carolina Pitsillides, Achilleas and Hottenga, Jouke Jan Willemsen, Gonneke Wood, Andrew R. Ji, Yingji Gao, Zishan Haworth, Simon Mitchell, Ruth E. and Chai, Jin Fang Aadahl, Mette Yao, Jie Manichaikul, Ani and Warren, Helen R. Ramirez, Julia Bork-Jensen, Jette Karhus, Line L. Goel, Anuj Sabater-Lleal, Maria Noordam, Raymond and Sidore, Carlo Fiorillo, Edoardo McDaid, Aaron F. and Marques-Vidal, Pedro Wielscher, Matthias Trompet, Stella and Sattar, Naveed Mollehave, Line T. Thuesen, Betina H. Munz, Matthias Zeng, Lingyao Huang, Jianfeng Yang, Bin Poveda, Alaitz Kurbasic, Azra Lamina, Claudia Forer, Lukas and Scholz, Markus Galesloot, Tessel E. Bradfield, Jonathan P. and Daw, E. Warwick Zmuda, Joseph M. Mitchell, Jonathan S. and Fuchsberger, Christian Christensen, Henry Brody, Jennifer A. and Feitosa, Mary F. Wojczynski, Mary K. Preuss, Michael and Mangino, Massimo Christofidou, Paraskevi Verweij, Niek and Benjamins, Jan W. Engmann, Jorgen Kember, Rachel L. Slieker, Roderick C. Lo, Ken Sin Zilhao, Nuno R. Phuong Le and Kleber, Marcus E. Delgado, Graciela E. Huo, Shaofeng Ikeda, Daisuke D. Iha, Hiroyuki Yang, Jian Liu, Jun Leonard, Hampton L. Marten, Jonathan Schmidt, Borge Arendt, Marina and Smyth, Laura J. Canadas-Garre, Marisa Wang, Chaolong and Nakatochi, Masahiro Wong, Andrew Hutri-Kahonen, Nina Sim, Xueling Xia, Rui Huerta-Chagoya, Alicia Fernandez-Lopez, Juan Carlos Lyssenko, Valeriya Ahmed, Meraj Jackson, Anne U. and Irvin, Marguerite R. Oldmeadow, Christopher Kim, Han-Na and Ryu, Seungho Timmers, Paul R. H. J. Arbeeva, Liubov Dorajoo, Rajkumar Lange, Leslie A. Chai, Xiaoran Prasad, Gauri and Lores-Motta, Laura Pauper, Marc Long, Jirong Li, Xiaohui and Theusch, Elizabeth Takeuchi, Fumihiko Spracklen, Cassandra N. and Loukola, Anu Bollepalli, Sailalitha Warner, Sophie C. and Wang, Ya Xing Wei, Wen B. Nutile, Teresa Ruggiero, Daniela and Sung, Yun Ju Hung, Yi-Jen Chen, Shufeng Liu, Fangchao and Yang, Jingyun Kentistou, Katherine A. Gorski, Mathias and 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. Pitkanen, Niina Cade, Brian E. Lee, Jiwon van Der Laan, Sander W. and Chitrala, Kumaraswamy Naidu Weiss, Stefan Zimmermann, Martina E. and Lee, Jong Young Choi, Hyeok Sun Nethander, Maria and Freitag-Wolf, Sandra Southam, Lorraine Rayner, Nigel W. and Wang, Carol A. Lin, Shih-Yi Wang, Jun-Sing Couture, Christian Lyytikainen, Leo-Pekka Nikus, Kjell and Cuellar-Partida, Gabriel Vestergaard, Henrik Hildalgo, Bertha and 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 and Highland, Heather M. Young, Kristin L. Kawaguchi, Takahisa and Thiery, Joachim Bis, Joshua C. Nadkarni, Girish N. Launer, Lenore J. Li, Huaixing Nalls, Mike A. Raitakari, Olli T. and Ichihara, Sahoko Wild, Sarah H. Nelson, Christopher P. and Campbell, Harry Jager, Susanne Nabika, Toru Al-Mulla, Fahd and Niinikoski, Harri Braund, Peter S. Kolcic, Ivana Kovacs, Peter Giardoglou, Tota Katsuya, Tomohiro Bhatti, Fatima and de Kleijn, Dominique de Borst, Gert J. Kim, Eung Kweon and Adams, Hieab H. H. Ikram, M. Arfan Zhu, Xiaofeng Asselbergs, Folkert W. Kraaijeveld, Adriaan O. Beulens, Joline W. J. and Shu, Xiao-Ou Rallidis, Loukianos S. Pedersen, Oluf Hansen, Torben Mitchell, Paul Hewitt, Alex W. Kahonen, Mika and Perusse, Louis Bouchard, Claude Tonjes, Anke Chen, Yii-Der Ida Pennell, Craig E. Mori, Trevor A. Lieb, Wolfgang and Franke, Andre Ohlsson, Claes Mellstrom, Dan Cho, Yoon Shin and Lee, Hyejin Yuan, Jian-Min Koh, Woon-Puay Rhee, Sang Youl Woo, Jeong-Taek Heid, Iris M. Stark, Klaus J. and Volzke, Henry Homuth, Georg Evans, Michele K. Zonderman, Alan B. Polasek, Ozren Pasterkamp, Gerard Hoefer, Imo E. and Redline, Susan Pahkala, Katja Oldehinkel, Albertine J. and Snieder, Harold Biino, Ginevra Schmidt, Reinhold Schmidt, Helena Chen, Y. Eugene Bandinelli, Stefania Dedoussis, George Thanaraj, Thangavel Alphonse Kardia, Sharon L. R. and Kato, Norihiro Schulze, Matthias B. Girotto, Giorgia Jung, Bettina Boger, Carsten A. Joshi, Peter K. Bennett, David A. and De Jager, Philip L. Lu, Xiangfeng Mamakou, Vasiliki and Brown, Morris Caulfield, Mark J. Munroe, Patricia B. Guo, Xiuqing Ciullo, Marina Jonas, Jost B. Samani, Nilesh J. and Kaprio, Jaakko Pajukanta, Paivi Adair, Linda S. Bechayda, Sonny Augustin de Silva, H. Janaka Wickremasinghe, Ananda R. and Krauss, Ronald M. Wu, Jer-Yuarn Zheng, Wei den Hollander, I, Anneke Bharadwaj, Dwaipayan Correa, Adolfo Wilson, James G. and Lind, Lars Heng, Chew-Kiat Nelson, Amanda E. Golightly, Yvonne M. Wilson, James F. Penninx, Brenda Kim, Hyung-Lae and Attia, John Scott, Rodney J. Rao, D. C. Arnett, Donna K. and Walker, Mark Koistinen, Heikki A. Chandak, Giriraj R. and Yajnik, Chittaranjan S. Mercader, Josep M. Tusie-Luna, Teresa and Aguilar-Salinas, Carlos A. Villalpando, Clicerio Gonzalez and Orozco, Lorena Fornage, Myriam Tai, E. Shyong van Dam, Rob M. Lehtimaki, Terho Chaturvedi, Nish Yokota, Mitsuhiro and Liu, Jianjun Reilly, Dermot F. McKnight, Amy Jayne Kee, Frank Jockel, Karl-Heinz McCarthy, I, Mark Palmer, Colin N. A. Vitart, Veronique Hayward, Caroline Simonsick, Eleanor and van Duijn, Cornelia M. Lu, Fan Qu, Jia Hishigaki, Haretsugu Lin, Xu Marz, 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 and Spector, Tim D. Loos, Ruth J. F. Province, Michael A. Psaty, Bruce M. Brandslund, Ivan Pramstaller, Peter P. Christensen, Kaare Ripatti, Samuli Widen, Elisabeth Hakonarson, Hakon and Grant, Struan F. A. Kiemeney, Lambertus A. L. M. de Graaf, Jacqueline Loeffler, Markus Kronenberg, Florian Gu, Dongfeng and Erdmann, Jeanette Schunkert, Heribert Franks, Paul W. and Linneberg, Allan Jukema, J. Wouter Khera, V, Amit Mannikko, Minna Jarvelin, Marjo-Riitta Kutalik, Zoltan Cucca, Francesco Mook-Kanamori, Dennis O. van Dijk, Ko Willems and Watkins, Hugh Strachan, David P. Grarup, Niels Sever, Peter and Poulter, Neil Rotter, I, Jerome Dantoft, Thomas M. and 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. and Boomsma, I, Dorret de Geus, Eco J. C. Cupples, L. Adrienne and van Meurs, Joyce B. J. Ghanbari, Mohsen Rsen, Penny Gordon-La and Huang, Wei Kim, Young Jin Tabara, Yasuharu Wareham, Nicholas J. Langenberg, Claudia Zeggini, Eleftheria and 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 and Kraft, Peter Martin, Nicholas G. Whitfield, John B. Abbas, Shahid Saleheen, Danish Walters, Robin G. Holmes, V, Michael and Black, Corri Smith, Blair H. Justice, Anne E. Baras, Aris Buring, Julie E. Ridker, Paul M. Chasman, I, Daniel and Kooperberg, Charles Wei, Wei-Qi Jarvik, Gail P. Namjou, Bahram Hayes, M. Geoffrey Ritchie, Marylyn D. Jousilahti, Pekka Salomaa, Veikko Hveem, Kristian Asvold, Bjorn Olav and Kubo, Michiaki Kamatani, Yoichiro Okada, Yukinori Murakami, Yoshinori Thorsteinsdottir, Unnur Stefansson, Kari Ho, Yuk-Lam Lynch, Julie A. Rader, Daniel J. Tsao, Philip S. and Chang, Kyong-Mi Cho, Kelly O'Donnell, Christopher J. and Gaziano, John M. Wilson, Peter Rotimi, Charles N. and Hazelhurst, Scott Ramsay, Michele Trembath, Richard C. van Heel, David A. Tamiya, Gen Yamamoto, Masayuki Kim, Bong-Jo and Mohlke, Karen L. Frayling, Timothy M. Hirschhorn, Joel N. and Kathiresan, Sekar Boehnke, Michael Natarajan, Pradeep and Peloso, Gina M. Brown, Christopher D. Morris, Andrew P. and Assimes, Themistocles L. Deloukas, Panos Sun, V, Yan Willer, Cristen J.

Abstract

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use(1). Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels(2), heart disease remains the leading cause of death worldwide(3). Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS(4-23) have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns(24). Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine(25), we anticipate that increased diversity of participants will lead to more accurate and equitable(26) application of polygenic scores in clinical practice.

Published
2021

232. sj-docx-2-fas-10.1177_19386400211001993 – Supplemental material for Patient Satisfaction Following Hallux Rigidus Treatment With a Synthetic Cartilage Implant

Author

Wonyong Lee, Wang, Carol, Prat, Dan, Wapner, Keith L., Chao, Wen, and Farber, Daniel C.

Subjects
viruses, FOS: Clinical medicine, embryonic structures, 110323 Surgery, 110604 Sports Medicine, biochemical phenomena, metabolism, and nutrition, FOS: Health sciences, 110314 Orthopaedics
Abstract

Supplemental material, sj-docx-2-fas-10.1177_19386400211001993 for Patient Satisfaction Following Hallux Rigidus Treatment With a Synthetic Cartilage Implant by Wonyong Lee, Carol Wang, Dan Prat, Keith L. Wapner, Wen Chao and Daniel C. Farber in Foot & Ankle Specialist

Published
2021
Full Text
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233. sj-docx-1-fas-10.1177_19386400211001993 – Supplemental material for Patient Satisfaction Following Hallux Rigidus Treatment With a Synthetic Cartilage Implant

Author

Wonyong Lee, Wang, Carol, Prat, Dan, Wapner, Keith L., Chao, Wen, and Farber, Daniel C.

Subjects
viruses, FOS: Clinical medicine, embryonic structures, 110323 Surgery, 110604 Sports Medicine, biochemical phenomena, metabolism, and nutrition, FOS: Health sciences, 110314 Orthopaedics
Abstract

Supplemental material, sj-docx-1-fas-10.1177_19386400211001993 for Patient Satisfaction Following Hallux Rigidus Treatment With a Synthetic Cartilage Implant by Wonyong Lee, Carol Wang, Dan Prat, Keith L. Wapner, Wen Chao and Daniel C. Farber in Foot & Ankle Specialist

Published
2021
Full Text
View/download PDF

234. The trans-ancestral genomic architecture of glycemic traits

Author

Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian'an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Chan, Kei Hang Katie, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Lorraine, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V R, Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P, Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J L, Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J C, Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M Arfan, Johnson, W Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R H J, Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Gonçalo R, Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, de Silva, H Janaka, Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L R, Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J F, Magnusson, Patrik K E, Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N A, Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I A, Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G M, Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C J, Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês, Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian'an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Chan, Kei Hang Katie, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Lorraine, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V R, Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P, Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J L, Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J C, Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M Arfan, Johnson, W Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R H J, Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Gonçalo R, Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, de Silva, H Janaka, Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L R, Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J F, Magnusson, Patrik K E, Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N A, Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I A, Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G M, Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C J, Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., and Barroso, Inês

Abstract

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

Published
2021
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235. Genetic association study of childhood aggression across raters, instruments, and age.

Author

Ip, Hill, Ip, Hill, van der Laan, Camiel, Krapohl, Eva, Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja, St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol, Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke, Adkins, Daniel, Border, Richard, Peterson, Roseann, Prinz, Joseph, Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer, Day, Felix, Hottenga, Jouke-Jan, Allegrini, Andrea, Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José, Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James, Vinkhuyzen, Anna, Shabalin, Andrey, Corley, Robin, Evans, Luke, Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth, Ehli, Erik, Hagenbeek, Fiona, De Zeeuw, Eveline, Van Beijsterveldt, Toos, Larsson, Henrik, Snieder, Harold, Verhulst, Frank, Amin, Najaf, Whipp, Alyce, Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard, Uitterlinden, André, Heath, Andrew, Madden, Pamela, Haavik, Jan, Harris, Jennifer, Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun, Njolstad, Pal, Lu, Qing, Rodriguez, Alina, Henders, Anjali, Mamun, Abdullah, Najman, Jackob, Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara, Silberg, Judy, Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, Raitakari, Olli, Ip, Hill, Ip, Hill, van der Laan, Camiel, Krapohl, Eva, Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja, St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol, Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke, Adkins, Daniel, Border, Richard, Peterson, Roseann, Prinz, Joseph, Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer, Day, Felix, Hottenga, Jouke-Jan, Allegrini, Andrea, Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José, Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James, Vinkhuyzen, Anna, Shabalin, Andrey, Corley, Robin, Evans, Luke, Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth, Ehli, Erik, Hagenbeek, Fiona, De Zeeuw, Eveline, Van Beijsterveldt, Toos, Larsson, Henrik, Snieder, Harold, Verhulst, Frank, Amin, Najaf, Whipp, Alyce, Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard, Uitterlinden, André, Heath, Andrew, Madden, Pamela, Haavik, Jan, Harris, Jennifer, Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun, Njolstad, Pal, Lu, Qing, Rodriguez, Alina, Henders, Anjali, Mamun, Abdullah, Najman, Jackob, Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara, Silberg, Judy, Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, and Raitakari, Olli

Abstract

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a po

Published
2021

236. 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. 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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., Phuong Le, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L., Marten, Jonathan, Schmidt, Borge, Arendt, Marina, Smyth, Laura J., Canadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kahonen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U., 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, Lores-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., Pitkanen, 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, Lyytikainen, 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, Jager, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, 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., Kahonen, Mika, Perusse, Louis, Bouchard, Claude, Tonjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellstrom, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Volzke, 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, Boger, 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, Paivi, 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, Koistinen, Heikki A., Chandak, Giriraj R., Yajnik, Chittaranjan S., Mercader, Josep M., Tusie-Luna, Teresa, Aguilar-Salinas, Carlos A., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimaki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jockel, 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, Marz, 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, Widen, 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, Mannikko, 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, Rsen, Penny Gordon-La, 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, Asvold, Bjorn 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, Michele, 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., Willer, Cristen J., 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, Karhus, 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., Phuong Le, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L., Marten, Jonathan, Schmidt, Borge, Arendt, Marina, Smyth, Laura J., Canadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kahonen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U., 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, Lores-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., Pitkanen, 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, Lyytikainen, 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, Jager, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, 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., Kahonen, Mika, Perusse, Louis, Bouchard, Claude, Tonjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellstrom, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Volzke, 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, Boger, 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, Paivi, 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, Koistinen, Heikki A., Chandak, Giriraj R., Yajnik, Chittaranjan S., Mercader, Josep M., Tusie-Luna, Teresa, Aguilar-Salinas, Carlos A., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimaki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jockel, 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, Marz, 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, Widen, 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, Mannikko, 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, Rsen, Penny Gordon-La, 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, Asvold, Bjorn 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, Michele, 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

237. Genetic association study of childhood aggression across raters, instruments, and age

Author

Ip, Hill F., van der Laan, Camiel M., Krapohl, Eva M.L., Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja M., St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol A., Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke R., Adkins, Daniel E., Border, Richard, Peterson, Roseann E., Prinz, Joseph A., Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer S., Day, Felix R., Hottenga, Jouke Jan, Allegrini, Andrea G., Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep Antoni, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José J., Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James G., Vinkhuyzen, Anna, Shabalin, Andrey A., Corley, Robin, Evans, Luke M., Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth E., Ehli, Erik A., Hagenbeek, Fiona A., De Zeeuw, Eveline, Van Beijsterveldt, Toos C.E.M., Larsson, Henrik, Snieder, Harold, Verhulst, Frank C., Amin, Najaf, Whipp, Alyce M., Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard J., Uitterlinden, André G., Heath, Andrew C., Madden, Pamela, Haavik, Jan, Harris, Jennifer R., Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun Peggy S., Njolstad, Pal Rasmus, Lu, Qing, Rodriguez, Alina, Henders, Anjali K., Mamun, Abdullah, Najman, Jackob M., Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara L., Silberg, Judy L., Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, Raitakari, Olli T., Perry, John R.B., Llop, Sabrina, Lopez-Espinosa, Maria Jose, Bønnelykke, Klaus, Bisgaard, Hans, Sunyer, Jordi, Lehtimäki, Terho, Arseneault, Louise, Standl, Marie, Heinrich, Joachim, Boden, Joseph, Pearson, John, Horwood, L. John, Kennedy, Martin, Poulton, Richie, Eaves, Lindon J., Maes, Hermine H., Hewitt, John, Copeland, William E., Costello, Elizabeth J., Williams, Gail M., Wray, Naomi, Järvelin, Marjo Riitta, McGue, Matt, Iacono, William, Caspi, Avshalom, Moffitt, Terrie E., Whitehouse, Andrew, Pennell, Craig E., Klump, Kelly L., Burt, S. Alexandra, Dick, Danielle M., Reichborn-Kjennerud, Ted, Martin, Nicholas G., Medland, Sarah E., Vrijkotte, Tanja, Kaprio, Jaakko, Tiemeier, Henning, Davey Smith, George, Hartman, Catharina A., Oldehinkel, Albertine J., Casas, Miquel, Ribasés, Marta, Lichtenstein, Paul, Lundström, Sebastian, Plomin, Robert, Bartels, Meike, Nivard, Michel G., Boomsma, Dorret I., Ip, Hill F., van der Laan, Camiel M., Krapohl, Eva M.L., Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja M., St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol A., Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke R., Adkins, Daniel E., Border, Richard, Peterson, Roseann E., Prinz, Joseph A., Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer S., Day, Felix R., Hottenga, Jouke Jan, Allegrini, Andrea G., Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep Antoni, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José J., Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James G., Vinkhuyzen, Anna, Shabalin, Andrey A., Corley, Robin, Evans, Luke M., Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth E., Ehli, Erik A., Hagenbeek, Fiona A., De Zeeuw, Eveline, Van Beijsterveldt, Toos C.E.M., Larsson, Henrik, Snieder, Harold, Verhulst, Frank C., Amin, Najaf, Whipp, Alyce M., Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard J., Uitterlinden, André G., Heath, Andrew C., Madden, Pamela, Haavik, Jan, Harris, Jennifer R., Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun Peggy S., Njolstad, Pal Rasmus, Lu, Qing, Rodriguez, Alina, Henders, Anjali K., Mamun, Abdullah, Najman, Jackob M., Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara L., Silberg, Judy L., Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, Raitakari, Olli T., Perry, John R.B., Llop, Sabrina, Lopez-Espinosa, Maria Jose, Bønnelykke, Klaus, Bisgaard, Hans, Sunyer, Jordi, Lehtimäki, Terho, Arseneault, Louise, Standl, Marie, Heinrich, Joachim, Boden, Joseph, Pearson, John, Horwood, L. John, Kennedy, Martin, Poulton, Richie, Eaves, Lindon J., Maes, Hermine H., Hewitt, John, Copeland, William E., Costello, Elizabeth J., Williams, Gail M., Wray, Naomi, Järvelin, Marjo Riitta, McGue, Matt, Iacono, William, Caspi, Avshalom, Moffitt, Terrie E., Whitehouse, Andrew, Pennell, Craig E., Klump, Kelly L., Burt, S. Alexandra, Dick, Danielle M., Reichborn-Kjennerud, Ted, Martin, Nicholas G., Medland, Sarah E., Vrijkotte, Tanja, Kaprio, Jaakko, Tiemeier, Henning, Davey Smith, George, Hartman, Catharina A., Oldehinkel, Albertine J., Casas, Miquel, Ribasés, Marta, Lichtenstein, Paul, Lundström, Sebastian, Plomin, Robert, Bartels, Meike, Nivard, Michel G., and Boomsma, Dorret I.

Abstract

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range ∣ rg∣ : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range ∣ rg∣ : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- an

Published
2021

238. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

Author

Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernández, Juan, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Kerick, Martin, Wang, Carol, Melton, Phillip, Elliot, Hannah R., Shin, Jean, Bernard, Manon, Yet, Idil, Smart, Melissa, Gorrie-Stone, Tyler, Bell, Jordana T., Heijmans, Bastiaan T., Mill, Jonathan, Relton, Caroline L., Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernández, Juan, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Kerick, Martin, Wang, Carol, Melton, Phillip, Elliot, Hannah R., Shin, Jean, Bernard, Manon, Yet, Idil, Smart, Melissa, Gorrie-Stone, Tyler, Bell, Jordana T., Heijmans, Bastiaan T., Mill, Jonathan, and Relton, Caroline L.

Abstract

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.

Published
2021

239. Genome-wide association analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Author

Eising, Else; https://orcid.org/0000-0001-9819-1260, Mirza-Schreiber, Nazanin; https://orcid.org/0000-0003-0836-8267, de Zeeuw, Eveline L; https://orcid.org/0000-0001-9042-7419, Wang, Carol A, Truong, Dongnhu T, Allegrini, Andrea G; https://orcid.org/0000-0003-4048-4292, Shapland, Chin Yang; https://orcid.org/0000-0002-5797-1241, Zhu, Gu; https://orcid.org/0000-0002-5691-1917, Wigg, Karen G, Gerritse, Margot, Molz, Barbara, Alagöz, Gökberk, Gialluisi, Alessandro; https://orcid.org/0000-0002-7388-4463, Abbondanza, Filippo; https://orcid.org/0000-0002-1799-5492, Rimfeld, Kaili; https://orcid.org/0000-0001-5139-065X, van Donkelaar, Marjolein; https://orcid.org/0000-0002-9112-2307, Liao, Zhijie, Jansen, Philip R; https://orcid.org/0000-0003-1550-2444, Andlauer, Till F M; https://orcid.org/0000-0002-2917-5889, Bates, Timothy C; https://orcid.org/0000-0002-1153-9007, Bernard, Manon, Blokland, Kirsten, Børglum, Anders D, Bourgeron, Thomas; https://orcid.org/0000-0001-8164-9220, Brandeis, Daniel, Ceroni, Fabiola, Dale, Philip S; https://orcid.org/0000-0002-7697-8510, Landerl, Karin; https://orcid.org/0000-0003-4074-0233, Lyytinen, Heikki, de Jong, Peter F, et al, Eising, Else; https://orcid.org/0000-0001-9819-1260, Mirza-Schreiber, Nazanin; https://orcid.org/0000-0003-0836-8267, de Zeeuw, Eveline L; https://orcid.org/0000-0001-9042-7419, Wang, Carol A, Truong, Dongnhu T, Allegrini, Andrea G; https://orcid.org/0000-0003-4048-4292, Shapland, Chin Yang; https://orcid.org/0000-0002-5797-1241, Zhu, Gu; https://orcid.org/0000-0002-5691-1917, Wigg, Karen G, Gerritse, Margot, Molz, Barbara, Alagöz, Gökberk, Gialluisi, Alessandro; https://orcid.org/0000-0002-7388-4463, Abbondanza, Filippo; https://orcid.org/0000-0002-1799-5492, Rimfeld, Kaili; https://orcid.org/0000-0001-5139-065X, van Donkelaar, Marjolein; https://orcid.org/0000-0002-9112-2307, Liao, Zhijie, Jansen, Philip R; https://orcid.org/0000-0003-1550-2444, Andlauer, Till F M; https://orcid.org/0000-0002-2917-5889, Bates, Timothy C; https://orcid.org/0000-0002-1153-9007, Bernard, Manon, Blokland, Kirsten, Børglum, Anders D, Bourgeron, Thomas; https://orcid.org/0000-0001-8164-9220, Brandeis, Daniel, Ceroni, Fabiola, Dale, Philip S; https://orcid.org/0000-0002-7697-8510, Landerl, Karin; https://orcid.org/0000-0003-4074-0233, Lyytinen, Heikki, de Jong, Peter F, and et al

Abstract

The use of spoken and written language is a capacity that is unique to humans. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The relevant genetic architecture is complex, heterogeneous, and multifactorial, and yet to be investigated with well-powered studies. Here, we present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, with total sample sizes ranging from 13,633 to 33,959 participants aged 5-26 years (12,411 to 27,180 for those with European ancestry, defined by principal component analyses). We identified a genome-wide significant association with word reading (rs11208009, p=1.098 × 10$^{−8}$) independent of known loci associated with intelligence or educational attainment. All five reading-/language-related traits had robust SNP-heritability estimates (0.13–0.26), and genetic correlations between them were modest to high. Using genomic structural equation modelling, we found evidence for a shared genetic factor explaining the majority of variation in word and nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS was performed to jointly analyse word and nonword reading, spelling, and phoneme awareness, maximizing power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with cortical surface area of the banks of the left superior temporal sulcus, a brain region with known links to processing of spoken and written language. Analysis of evolutionary annotations on the lineage that led to modern humans showed enriched heritability in regions depleted of Neander

Published
2021

240. Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty

Author

Cousminer, Diana L., Stergiakouli, Evangelia, Berry, Diane J., Ang, Wei, Groen-Blokhuis, Maria M., Körner, Antje, Siitonen, Niina, Ntalla, Ioanna, Marinelli, Marcella, Perry, John R.B., Kettunen, Johannes, Jansen, Rick, Surakka, Ida, Timpson, Nicholas J., Ring, Susan, Mcmahon, George, Power, Chris, Wang, Carol, Kähönen, Mika, Viikari, Jorma, Lehtimäki, Terho, Middeldorp, Christel M., Hulshoff Pol, Hilleke E., Neef, Madlen, Weise, Sebastian, Pahkala, Katja, Niinikoski, Harri, Zeggini, Eleftheria, Panoutsopoulou, Kalliope, Bustamante, Mariona, Penninx, Brenda W.J.H., Murabito, Joanne, Torrent, Maties, Dedoussis, George V., Kiess, Wieland, Boomsma, Dorret I., Pennell, Craig E., Raitakari, Olli T., Hyppönen, Elina, Davey Smith, George, Ripatti, Samuli, McCarthy, Mark I., and Widén, Elisabeth

Published
2014
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241. Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Author

Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian’an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O’Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimäki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietiläinen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josée, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin D.

Abstract

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 588,452 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.

Published
2023
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242. Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth

Author

Beaumont, Robin N., Flatley, Christopher, Vaudel, Marc, Wu, Xiaoping, Chen, Jing, Moen, Gunn-Helen, Skotte, Line, Helgeland, Øyvind, Solé-Navais, Pol, Banasik, Karina, Albiñana, Clara, Ronkainen, Justiina, Fadista, João, Stinson, Sara Elizabeth, Trajanoska, Katerina, Wang, Carol A., Westergaard, David, Srinivasan, Sundararajan, Sánchez-Soriano, Carlos, Bilbao, Jose Ramon, Allard, Catherine, Groleau, Marika, Kuulasmaa, Teemu, Leirer, Daniel J., White, Frédérique, Jacques, Pierre-Étienne, Cheng, Haoxiang, Hao, Ke, Andreassen, Ole A., Åsvold, Bjørn Olav, Atalay, Mustafa, Bhatta, Laxmi, Bouchard, Luigi, Brumpton, Ben Michael, Brunak, Søren, Bybjerg-Grauholm, Jonas, Ebbing, Cathrine, Elliott, Paul, Engelbrechtsen, Line, Erikstrup, Christian, Estarlich, Marisa, Franks, Stephen, Gaillard, Romy, Geller, Frank, Grove, Jakob, Hougaard, David M., Kajantie, Eero, Morgen, Camilla S., Nohr, Ellen A., Nyegaard, Mette, Palmer, Colin N. A., Pedersen, Ole Birger, Rivadeneira, Fernando, Sebert, Sylvain, Shields, Beverley M., Stoltenberg, Camilla, Surakka, Ida, Thørner, Lise Wegner, Ullum, Henrik, Vaarasmaki, Marja, Vilhjalmsson, Bjarni J., Willer, Cristen J., Lakka, Timo A., Gybel-Brask, Dorte, Bustamante, Mariona, Hansen, Torben, Pearson, Ewan R., Reynolds, Rebecca M., Ostrowski, Sisse R., Pennell, Craig E., Jaddoe, Vincent W. V., Felix, Janine F., Hattersley, Andrew T., Melbye, Mads, Lawlor, Deborah A., Hveem, Kristian, Werge, Thomas, Nielsen, Henriette Svarre, Magnus, Per, Evans, David M., Jacobsson, Bo, Järvelin, Marjo-Riitta, Zhang, Ge, Hivert, Marie-France, Johansson, Stefan, Freathy, Rachel M., Feenstra, Bjarke, and Njølstad, Pål R.

Abstract

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n= 65,405), maternal (n= 61,228) and paternal (n= 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.

Published
2023
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243. China IP Updates: September 2021 (Issue 1) - 14 Sep 2021

Author

Wang, Carol

Subjects
Music industry -- Intellectual property -- Market share, Copyright law -- Interpretation and construction, Company market share, Business, international
Abstract

Too much of a good thing? Tencent and its 80% market share in exclusive music copyright 腾讯解除网络音乐独家版权 Date: 2021-08-31 Trying to increase your market share in China please? If that's [...]

Published
2021

244. Correction: Corrigendum: Rare coding variants and X-linked loci associated with age at menarche

Author

Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tõnu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Mägi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., Rivadeneira, Fernando, Rudan, Igor, Sala, Cinzia F., Schlessinger, David, Scott, Robert A., Stöckl, Doris, Visser, Jenny A., Völker, Uwe, Vozzi, Diego, Wilson, James G., Zygmunt, Marek, Boerwinkle, Eric, Buring, Julie E., Crisponi, Laura, Easton, Douglas F., Hayward, Caroline, Hu, Frank B., Liu, Simin, Metspalu, Andres, Pennell, Craig E., Ridker, Paul M., Strauch, Konstantin, Streeten, Elizabeth A., Toniolo, Daniela, Uitterlinden, André G., Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Wellons, Melissa, Franceschini, Nora, Chasman, Daniel I., Thorsteinsdottir, Unnur, Murray, Anna, Stefansson, Kari, Murabito, Joanne M., Ong, Ken K., and Perry, John R. B.

Published
2015
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247. Variants associated with HHIP expression have sex-differential effects on lung function

Author

Fawcett, Katherine A., primary, Obeidat, Ma'en, additional, Melbourne, Carl A., additional, Shrine, Nick, additional, Guyatt, Anna L., additional, John, Catherine, additional, Luan, Jian'an, additional, Richmond, Anne, additional, Moksnes, Marta R., additional, Granell, Raquel, additional, Weiss, Stefan, additional, Imboden, Medea, additional, May-Wilson, Sebastian, additional, Hysi, Pirro, additional, Boutin, Thibaud S., additional, Portas, Laura, additional, Flexeder, Claudia, additional, Harris, Sarah E., additional, Wang, Carol A., additional, Lyytikäinen, Leo-Pekka, additional, Palviainen, Teemu, additional, Foong, Rachel E., additional, Keidel, Dirk, additional, Minelli, Cosetta, additional, Langenberg, Claudia, additional, Bossé, Yohan, additional, Van den Berge, Maarten, additional, Sin, Don D., additional, Hao, Ke, additional, Campbell, Archie, additional, Porteous, David, additional, Padmanabhan, Sandosh, additional, Smith, Blair H., additional, Evans, David M., additional, Ring, Sue, additional, Langhammer, Arnulf, additional, Hveem, Kristian, additional, Willer, Cristen, additional, Ewert, Ralf, additional, Stubbe, Beate, additional, Pirastu, Nicola, additional, Klaric, Lucija, additional, Joshi, Peter K., additional, Patasova, Karina, additional, Massimo, Mangino, additional, Polasek, Ozren, additional, Starr, John M., additional, Karrasch, Stefan, additional, Strauch, Konstantin, additional, Meitinger, Thomas, additional, Rudan, Igor, additional, Rantanen, Taina, additional, Pietiläinen, Kirsi, additional, Kähönen, Mika, additional, Raitakari, Olli T., additional, Hall, Graham L., additional, Sly, Peter D., additional, Pennell, Craig E., additional, Kaprio, Jaakko, additional, Lehtimäki, Terho, additional, Vitart, Veronique, additional, Deary, Ian J., additional, Jarvis, Debbie, additional, Wilson, James F., additional, Spector, Tim, additional, Probst-Hensch, Nicole, additional, Wareham, Nicholas J., additional, Völzke, Henry, additional, Henderson, John, additional, Strachan, David P., additional, Brumpton, Ben M., additional, Hayward, Caroline, additional, Hall, Ian P., additional, Tobin, Martin D., additional, and Wain, Louise V., additional

Published
2021
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250. Efficacy and Safety of Acupuncture and or Moxibustion for Managing Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.

Author

Weiting Liu, Chunfeng Wang, Carol, Khui Hung Lee, Xiaopeng Ma, and Kang, Timothy Leen

Subjects
*TREATMENT of dysmenorrhea, *ONLINE information services, *MOXIBUSTION, *META-analysis, *MEDICAL information storage & retrieval systems, *CONFIDENCE intervals, *ACUPUNCTURE, *SYSTEMATIC reviews, *TREATMENT effectiveness, *DESCRIPTIVE statistics, *CHI-squared test, *MEDLINE, *PATIENT safety, *DISEASE management, *PAIN management
Abstract

Acupuncture and moxibustion have been accepted as add-on options for primary dysmenorrhea (PD); however, the clinical evidence is still inadequate. We searched AMED, CENTRAL, EMBASE, PubMed, Web of Science, CBM, CNKI, VIP, Wangfang database, ANZCTR, ClinicalTrials.gov, and the WHO ICTRP, from their inception to February 2021. The pooled analysis of 13 RCTs with 675 participants for VAS showed that acupuncture and moxibustion were more effective in managing PD than the control group with the MD of - 1.93 (95% Cl [-2.80, - 1.06] and -2.67 (95% Cl [-4.96, -0.38]). With the CMSS, seven studies with 487 participants showed that these modalities were more effective than the control group with the MD of -7.58 (95% Cl [-10.97, -4.19]) and -3.78 (95% Cl [-6.90, -0.66]). The findings indicated that acupuncture and moxibustion could relieve pain effectively and has fewer adverse events (AEs) in managing PD. [ABSTRACT FROM AUTHOR]

Published
2022
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