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51. The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT).

Author

Lu, Robert, ORourke, Julienne, Sobinoff, Alexander, Allen, Joshua, Nelson, Christopher, Tomlinson, Christopher, Lee, Michael, Reddel, Roger, Deans, Andrew, and Pickett, Hilda

Subjects
Carrier Proteins, Cell Line, Tumor, DNA Helicases, DNA Replication, DNA Topoisomerases, Type I, DNA-Binding Proteins, HCT116 Cells, HEK293 Cells, HeLa Cells, Humans, Neoplasms, Nuclear Proteins, RecQ Helicases, Telomere, Telomere Homeostasis
Abstract

The collapse of stalled replication forks is a major driver of genomic instability. Several committed mechanisms exist to resolve replication stress. These pathways are particularly pertinent at telomeres. Cancer cells that use Alternative Lengthening of Telomeres (ALT) display heightened levels of telomere-specific replication stress, and co-opt stalled replication forks as substrates for break-induced telomere synthesis. FANCM is a DNA translocase that can form independent functional interactions with the BLM-TOP3A-RMI (BTR) complex and the Fanconi anemia (FA) core complex. Here, we demonstrate that FANCM depletion provokes ALT activity, evident by increased break-induced telomere synthesis, and the induction of ALT biomarkers. FANCM-mediated attenuation of ALT requires its inherent DNA translocase activity and interaction with the BTR complex, but does not require the FA core complex, indicative of FANCM functioning to restrain excessive ALT activity by ameliorating replication stress at telomeres. Synthetic inhibition of FANCM-BTR complex formation is selectively toxic to ALT cancer cells.

Published
2019

52. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author

Prins, Bram P, Mead, Timothy J, Brody, Jennifer A, Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A, van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T, Gabriel, George C, Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M, Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching-Ti, Lyytikäinen, Leo-Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V, Verweij, Niek, Warren, Helen R, Weiss, Stefan, Alonso, Alvaro, Arnar, David O, Bots, Michiel L, de Boer, Rudolf A, Dominiczak, Anna F, Eijgelsheim, Mark, Ellinor, Patrick T, Guo, Xiuqing, Felix, Stephan B, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Huang, Paul L, Jukema, JW, Kähönen, Mika, Kors, Jan A, Lambiase, Pier D, Launer, Lenore J, Li, Man, Linneberg, Allan, Nelson, Christopher P, Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M, Raitakari, Olli T, Rice, Kenneth M, Rotter, Jerome I, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Tim D, Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G, Xie, Zhijun, Asselbergs, Folkert W, Dörr, Marcus, van Duijn, Cornelia M, Gasparini, Paolo, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J, Lubitz, Steven A, Mook-Kanamori, Dennis O, Conti, Francesco J, Newton-Cheh, Christopher H, Rosand, Jonathan, Rudan, Igor, and Samani, Nilesh J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Human Genome, Heart Disease, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, ADAMTS Proteins, Animals, Black People, Connexin 43, Electrocardiography, Exome, Female, Gene Expression, Gene Expression Profiling, Genetic Loci, Genome-Wide Association Study, Heart Conduction System, Humans, Male, Mice, Middle Aged, Myocardium, Open Reading Frames, Polymorphism, Single Nucleotide, White People, Exome Sequencing, Exome chip, Conduction, ADAMTS6, Meta-analysis, Environmental Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundGenome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.ResultsHere, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.ConclusionsOur approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.

Published
2018

53. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids

Author

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

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

Author

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

Published
2022
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57. Modeling the SBC Tanzania Production-Distribution Logistics Network

Author

Dzupire, Nelson Christopher, Nkansah-Gyekye, Yaw, and Mirau, Silas Steven

Subjects
Mathematics - Optimization and Control
Abstract

The increase in customer expectation in terms of cost and services rendered, coupled with competitive business environment and uncertainty in cost of raw materials have posed challenges on effective supply chain engineering making it essential to do cost-benefit analysis before making final decisions on production distribution logistics. This paper provides a conceptual model that provide guidance in supply chain decision making for business expansion. It presents a mathematical model for production-distribution of an integrated supply chain derived from current operations of SBC Tanzania Ltd which is a major supply chain that manages products' distribution in whole of Tanzania. In addition to finding the optimal cost, we also carried out a sensitivity analysis on the model so as to find ways in which the company can expand at optimal cost, while meeting customers' demands. Genetic algorithms is used to run the simulation for their efficient in solving combinatorial problems.

Published
2017

58. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Hege Aamodt, Anne, Heidi Skogholt, Anne, Brumpton, Ben M, Willer, Cristen J, Sandset, Else C, Kristoffersen, Espen S, Ellekjær, Hanne, Heuch, Ingrid, Nielsen, Jonas B, Hagen, Knut, Hveem, Kristian, Fritsche, Lars G, Thomas, Laurent F, Pedersen, Linda M, Gabrielsen, Maiken E, Holmen, Oddgeir L, Børte, Sigrid, Zhou, Wei, Abboud, Shérine, Pandolfo, Massimo, Thijs, Vincent, Leys, Didier, Bodenant, Marie, Louillet, Fabien, Touzé, Emmanuel, Mas, Jean-Louis, Samson, Yves, Leder, Sara, Léger, Anne, Deltour, Sandrine, Crozier, Sophie, Méresse, Isabelle, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Béjot, Yannick, Decavel, Pierre, Medeiros, Elizabeth, Montiel, Paola, Moulin, Thierry, Vuillier, Fabrice, Dallongeville, Jean, Metso, Antti J, Metso, Tiina, Tatlisumak, Turgut, Grond-Ginsbach, Caspar, Lichy, Christoph, Kloss, Manja, Werner, Inge, Arnold, Marie-Luise, Dos Santos, Michael, Grau, Armin, Dichgans, Martin, Thomas-Feles, Constanze, Weber, Ralf, Brandt, Tobias, Pezzini, Alessandro, De Giuli, Valeria, Caria, Filomena, Poli, Loris, Padovani, Alessandro, Bersano, Anna, Lanfranconi, Silvia, Beretta, Simone, Ferrarese, Carlo, Giacolone, Giacomo, Paolucci, Stefano, Lyrer, Philippe, Engelter, Stefan, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Bonati, Leo, Gensicke, Henrik, Amort, Margareth, Markus, Hugh, Majersik, Jennifer, Worrall, Bradford, Southerland, Andrew, Cole, John, Kittner, Steven, Evangelou, Evangelos, Warren, Helen R, Gao, He, Ntritsos, Georgios, Dimou, Niki, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Peter Prins, Bram, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Connell, John, de Mutsert, Renée, Doney, Alex SF, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Yusuf Demirkale, Cumhur, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Mesut Erzurumluoglu, A, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Wouter Jukema, J, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David CM, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth JF, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O’Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, WJH Penninx, Brenda, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Tri Nguyen, Quang, Raitakari, Olli T, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna MM, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin NA, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Psaty, Bruce M., Wain, Louise V, Elliott, Paul, Caulfield, Mark J, Gormley, Padhraig, Anttila, Verneri, Palta, Priit, Esko, Tonu, Pers, Tune H, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Ridker, Paul M, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Arfan Ikram, M, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Akiyama, Masato, Alg, Varinder S., Børte, Sigrid, Broderick, Joseph P., Brumpton, Ben M., Dauvillier, Jérôme, Desal, Hubert, Dina, Christian, Friedrich, Christoph M., Gaál-Paavola, Emília I., Gentric, Jean-Christophe, Hirsch, Sven, Hostettler, Isabel C., Houlden, Henry, Hveem, Kristian, Jääskeläinen, Juha E., Johnsen, Marianne Bakke, Li, Liming, Lin, Kuang, Lindgren, Antti, Martin, Olivier, Matsuda, Koichi, Millwood, Iona Y., Naggara, Olivier, Niemelä, Mika, Pera, Joanna, Redon, Richard, Rouleau, Guy A., Sandvei, Marie Søfteland, Schilling, Sabine, Shotar, Eimad, Slowik, Agnieszka, Terao, Chikashi, Verschuren, W. M. Monique, Walters, Robin G., Werring, David J., Willer, Cristen J., Woo, Daniel, Worrall, Bradford B., and Zhou, Sirui

Published
2023
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59. The power of genetic diversity in genome-wide association studies of lipids

Author

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

Published
2021
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61. Emergent chirality in the electric polarization texture of titanate superlattices

Author

Shafer, Padraic, García-Fernández, Pablo, Aguado-Puente, Pablo, Damodaran, Anoop R, Yadav, Ajay K, Nelson, Christopher T, Hsu, Shang-Lin, Wojdeł, Jacek C, Íñiguez, Jorge, Martin, Lane W, Arenholz, Elke, Junquera, Javier, and Ramesh, Ramamoorthy

Subjects
Physical Sciences, Condensed Matter Physics, chirality, electric polarization, topological textures, resonant soft X-ray diffraction, second-principles calculations
Abstract

Chirality is a geometrical property by which an object is not superimposable onto its mirror image, thereby imparting a handedness. Chirality determines many important properties in nature-from the strength of the weak interactions according to the electroweak theory in particle physics to the binding of enzymes with naturally occurring amino acids or sugars, reactions that are fundamental for life. In condensed matter physics, the prediction of topologically protected magnetic skyrmions and related spin textures in chiral magnets has stimulated significant research. If the magnetic dipoles were replaced by their electrical counterparts, then electrically controllable chiral devices could be designed. Complex oxide BaTiO3/SrTiO3 nanocomposites and PbTiO3/SrTiO3 superlattices are perfect candidates, since "polar vortices," in which a continuous rotation of ferroelectric polarization spontaneously forms, have been recently discovered. Using resonant soft X-ray diffraction, we report the observation of a strong circular dichroism from the interaction between circularly polarized light and the chiral electric polarization texture that emerges in PbTiO3/SrTiO3 superlattices. This hallmark of chirality is explained by a helical rotation of electric polarization that second-principles simulations predict to reside within complex 3D polarization textures comprising ordered topological line defects. The handedness of the texture can be topologically characterized by the sign of the helicity number of the chiral line defects. This coupling between the optical and novel polar properties could be exploited to encode chiral signatures into photon or electron beams for information processing.

Published
2018

62. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

Author

Bihlmeyer, Nathan A, Brody, Jennifer A, Smith, Albert Vernon, Warren, Helen R, Lin, Honghuang, Isaacs, Aaron, Liu, Ching-Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M, Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E, Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P, van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Bis, Joshua C, Austin, Tom, Chen, Yii-Der Ida, Psaty, Bruce M, Harrris, Tamara B, Launer, Lenore J, Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L, Xie, Zhijun, Ellinor, Patrick T, Kors, Jan A, Campbell, Archie, Murray, Alison D, Nelson, Christopher P, Tobin, Martin D, Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Lin, Henry J, Taylor, Kent D, de Mutsert, Renée, Trompet, Stella, Jukema, J Wouter, Maan, Arie C, Stricker, Bruno HC, Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Raitakari, Olli T, Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B, Lubitz, Steven A, van Duijn, Cornelia M, Newton-Cheh, Christopher H, Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J, Kanters, Jørgen K, Wilson, James G, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Rotter, Jerome I, Mook-Kanamori, Dennis O, Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E, and Sotoodehnia, Nona

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Prevention, Genetics, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Antiporters, DNA-Binding Proteins, Electrocardiography, Exome, Genome-Wide Association Study, Humans, Long QT Syndrome, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Receptors, Calcium-Sensing, Transcription Factors, arrhythmias, cardiac, death, sudden, cardiac, genetics, genome, humans, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundQT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest.Methods and resultsWe performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci.ConclusionsOur analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.

Published
2018

63. Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure

Author

Ganji-Arjenaki, Mahboube, primary, Kamali, Zoha, additional, Evangelou, Evangelos, additional, Warren, Helen R., additional, Gao, He, additional, Ntritsos, Georgios, additional, Dimou, Niki, additional, Esko, Tonu, additional, Mägi, Reedik, additional, Milani, Lili, additional, Almgren, Peter, additional, Boutin, Thibaud, additional, Debette, Stéphanie, additional, Ding, Jun, additional, Giulianini, Franco, additional, Holliday, Elizabeth G., additional, Jackson, Anne U., additional, Li -Gao, Ruifang, additional, Lin, Wei -Yu, additional, Luan, Jian'an, additional, Mangino, Massimo, additional, Oldmeadow, Christopher, additional, Prins, Bram Peter, additional, Qian, Yong, additional, Sargurupremraj, Muralidharan, additional, Shah, Nabi, additional, Surendran, Praveen, additional, Thériault, Sébastien, additional, Verweij, Niek, additional, Willems, Sara M., additional, Zhao, Jing -Hua, additional, Amouyel, Philippe, additional, Connell, John, additional, de Mutsert, Renée, additional, Doney, Alex S.F., additional, Farrall, Martin, additional, Menni, Cristina, additional, Morris, Andrew D., additional, Noordam, Raymond, additional, Paré, Guillaume, additional, Poulter, Neil R., additional, Shields, Denis C., additional, Stanton, Alice, additional, Thom, Simon, additional, Abecasis, Gonçalo, additional, Amin, Najaf, additional, Arking, Dan E., additional, Ayers, Kristin L., additional, Barbieri, Caterina M., additional, Batini, Chiara, additional, Bis, Joshua C., additional, Blake, Tineka, additional, Bochud, Murielle, additional, Boehnke, Michael, additional, Boerwinkle, Eric, additional, Boomsma, Dorret I., additional, Bottinger, Erwin P., additional, Braund, Peter S., additional, Brumat, Marco, additional, Campbell, Archie, additional, Campbell, Harry, additional, Chakravarti, Aravinda, additional, Chambers, John C., additional, Chauhan, Ganesh, additional, Ciullo, Marina, additional, Cocca, Massimiliano, additional, Collins, Francis, additional, Cordell, Heather J., additional, Davies, Gail, additional, de Borst, Martin H., additional, de Geus, Eco J., additional, Deary, Ian J., additional, Deelen, Joris, additional, Del Greco M, Fabiola, additional, Demirkale, Cumhur Yusuf, additional, Dörr, Marcus, additional, Ehret, Georg B., additional, Elosua, Roberto, additional, Enroth, Stefan, additional, Erzurumluoglu, A. Mesut, additional, Ferreira, Teresa, additional, Frånberg, Mattias, additional, Franco, Oscar H., additional, Gandin, Ilaria, additional, Gasparini, Paolo, additional, Giedraitis, Vilmantas, additional, Gieger, Christian, additional, Girotto, Giorgia, additional, Goel, Anuj, additional, Gow, Alan J., additional, Gudnason, Vilmundur, additional, Guo, Xiuqing, additional, Gyllensten, Ulf, additional, Hamsten, Anders, additional, Harris, Tamara B., additional, Harris, Sarah E., additional, Hartman, Catharina A., additional, Havulinna, Aki S., additional, Hicks, Andrew A., additional, Hofer, Edith, additional, Hofman, Albert, additional, Hottenga, Jouke-Jan, additional, Huffman, Jennifer E., additional, Hwang, Shih-Jen, additional, Ingelsson, Erik, additional, James, Alan, additional, Jansen, Rick, additional, Jarvelin, Marjo -Riitta, additional, Joehanes, Roby, additional, Johansson, Åsa, additional, Johnson, Andrew D., additional, Joshi, Peter K., additional, Jousilahti, Pekka, additional, Jukema, J. Wouter, additional, Jula, Antti, additional, Kähönen, Mika, additional, Kathiresan, Sekar, additional, Keavney, Bernard D., additional, Khaw, Kay-Tee, additional, Knekt, Paul, additional, Knight, Joanne, additional, Kolcic, Ivana, additional, Kooner, Jaspal S., additional, Koskinen, Seppo, additional, Kristiansson, Kati, additional, Kutalik, Zoltan, additional, Laan, Maris, additional, Larson, Marty, additional, Launer, Lenore J., additional, Lehne, Benjamin, additional, Lehtimäki, Terho, additional, Liewald, David C.M., additional, Lin, Li, additional, Lind, Lars, additional, Lindgren, Cecilia M., additional, Liu, YongMei, additional, Loos, Ruth J.F., additional, Lopez, Lorna M., additional, Lu, Yingchang, additional, Lyytikäinen, Leo-Pekka, additional, Mahajan, Anubha, additional, Mamasoula, Chrysovalanto, additional, Marrugat, Jaume, additional, Marten, Jonathan, additional, Milaneschi, Yuri, additional, Morgan, Anna, additional, Morris, Andrew P., additional, Morrison, Alanna C., additional, Munson, Peter J., additional, Nalls, Mike A., additional, Nandakumar, Priyanka, additional, Nelson, Christopher P., additional, Niiranen, Teemu, additional, Nolte, Ilja M., additional, Nutile, Teresa, additional, Oldehinkel, Albertine J., additional, Oostra, Ben A., additional, O'Reilly, Paul F., additional, Org, Elin, additional, Padmanabhan, Sandosh, additional, Palmas, Walter, additional, Palotie, Aarno, additional, Pattie, Alison, additional, Penninx, Brenda W.J.H., additional, Perola, Markus, additional, Peters, Annette, additional, Polasek, Ozren, additional, Pramstaller, Peter P., additional, Nguyen, Quang Tri, additional, Raitakari, Olli T., additional, Rettig, Rainer, additional, Rice, Kenneth, additional, Ridker, Paul M., additional, Ried, Janina S., additional, Riese, Harriëtte, additional, Ripatti, Samuli, additional, Robino, Antonietta, additional, Rose, Lynda M., additional, Rotter, Jerome I., additional, Rudan, Igor, additional, Ruggiero, Daniela, additional, Saba, Yasaman, additional, Sala, Cinzia F., additional, Salomaa, Veikko, additional, Samani, Nilesh J., additional, Sarin, Antti-Pekka, additional, Schmidt, Reinhold, additional, Schmidt, Helena, additional, Shrine, Nick, additional, Siscovick, David, additional, Smith, Albert V., additional, Snieder, Harold, additional, Sõber, Siim, additional, Sorice, Rossella, additional, Starr, John M., additional, Stott, David J., additional, Strachan, David P., additional, Strawbridge, Rona J., additional, Sundström, Johan, additional, Swertz, Morris A., additional, Taylor, Kent D., additional, Teumer, Alexander, additional, Tobin, Martin D., additional, Tomaszewski, Maciej, additional, Toniolo, Daniela, additional, Traglia, Michela, additional, Trompet, Stella, additional, Tuomilehto, Jaakko, additional, Tzourio, Christophe, additional, Uitterlinden, André G., additional, Vaez, Ahmad, additional, van der Most, Peter J., additional, van Duijn, Cornelia M., additional, Verwoert, Germaine C., additional, Vitart, Veronique, additional, Völker, Uwe, additional, Vollenweider, Peter, additional, Vuckovic, Dragana, additional, Watkins, Hugh, additional, Wild, Sarah H., additional, Willemsen, Gonneke, additional, Wilson, James F., additional, Wright, Alan F., additional, Yao, Jie, additional, Zemunik, Tatijana, additional, Zhang, Weihua, additional, Attia, John R., additional, Butterworth, Adam S., additional, Chasman, Daniel I., additional, Conen, David, additional, Cucca, Francesco, additional, Danesh, John, additional, Hayward, Caroline, additional, Howson, Joanna M.M., additional, Laakso, Markku, additional, Lakatta, Edward G., additional, Langenberg, Claudia, additional, Melander, Olle, additional, Mook-Kanamori, Dennis O., additional, Palmer, Colin N.A., additional, Risch, Lorenz, additional, Scott, Robert A., additional, Scott, Rodney J., additional, Sever, Peter, additional, Spector, Tim D., additional, van der Harst, Pim, additional, Wareham, Nicholas J., additional, Zeggini, Eleftheria, additional, Levy, Daniel, additional, Munroe, Patricia B., additional, Newton-Cheh, Christopher, additional, Brown, Morris J., additional, Metspalu, Andres, additional, Psaty, Bruce M., additional, Wain, Louise V., additional, Elliott, Paul, additional, Caulfield, Mark J., additional, Sardari, Soroush, additional, and de Borst, Martin, additional

Published
2024
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65. Polygenic basis and biomedical consequences of telomere length variation

Author

Codd, Veryan, Wang, Qingning, Allara, Elias, Musicha, Crispin, Kaptoge, Stephen, Stoma, Svetlana, Jiang, Tao, Hamby, Stephen E., Braund, Peter S., Bountziouka, Vasiliki, Budgeon, Charley A., Denniff, Matthew, Swinfield, Chloe, Papakonstantinou, Manolo, Sheth, Shilpi, Nanus, Dominika E., Warner, Sophie C., Wang, Minxian, Khera, Amit V., Eales, James, Ouwehand, Willem H., Thompson, John R., Di Angelantonio, Emanuele, Wood, Angela M., Butterworth, Adam S., Danesh, John N., Nelson, Christopher P., and Samani, Nilesh J.

Published
2021
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66. The Nature of Electron Transport and visible light absorption in Strontium Niobate -- A Plasmonic Water Splitter

Author

Wan, Dongyang, Zhao, Yongliang, Cai, Yao, Asmara, Teguh Citra, Huang, Zhen, Chen, Jianqiang, Hong, Jindui, Nelson, Christopher T., Motapothula, Mallikarjuna Rao, Yan, Bixing, Xu, Rong, Zheng, Haimei, Ariando, Rusydi, Andrivo, Minor, Andrew, Breese, Mark B. H., Asta, Mark, Xu, Qinghua, and Venkatesan, T.

Subjects
Condensed Matter - Materials Science
Abstract

Semiconductor compounds are widely used for water splitting applications, where photo-generated electron-hole pairs are exploited to induce catalysis. Recently, powders of a metallic oxide (Sr$_{1-x}$NbO$_3$, 0.03 < x < 0.20) have shown competitive photocatalytic efficiency, opening up the material space available for finding optimizing performance in water-splitting applications. The origin of the visible light absorption in these powders was reported to be due to an interband transition and the charge carrier separation was proposed to be due to the high carrier mobility of this material. In the current work we have prepared epitaxial thin films of Sr$_{0.94}$NbO$_{3+{\delta}}$ and found that the bandgap of this material is ~4.1 eV, which is very large. Surprisingly the carrier density of the conducting phase reaches 10$^{22}$ cm$^{-3}$, which is only one order smaller than that of elemental metals and the carrier mobility is only 2.47 cm$^2$/(V$\cdot$s). Contrary to earlier reports, the visible light absorption at 1.8 eV (~688 nm) is due to the bulk plasmon resonance, arising from the large carrier density, instead of an interband transition. Excitation of the plasmonic resonance results in a multifold enhancement of the lifetime of charge carriers. Thus we propose that the hot charge carriers generated from decay of plasmons produced by optical absorption is responsible for the water splitting efficiency of this material under visible light irradiation.

Published
2016
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68. Discovery of novel heart rate-associated loci using the Exome Chip

Author

van den Berg, Marten E, Warren, Helen R, Cabrera, Claudia P, Verweij, Niek, Mifsud, Borbala, Haessler, Jeffrey, Bihlmeyer, Nathan A, Fu, Yi-Ping, Weiss, Stefan, Lin, Henry J, Grarup, Niels, Li-Gao, Ruifang, Pistis, Giorgio, Shah, Nabi, Brody, Jennifer A, Müller-Nurasyid, Martina, Lin, Honghuang, Mei, Hao, Smith, Albert V, Lyytikäinen, Leo-Pekka, Hall, Leanne M, van Setten, Jessica, Trompet, Stella, Prins, Bram P, Isaacs, Aaron, Radmanesh, Farid, Marten, Jonathan, Entwistle, Aiman, Kors, Jan A, Silva, Claudia T, Alonso, Alvaro, Bis, Joshua C, de Boer, Rudolf, de Haan, Hugoline G, de Mutsert, Renée, Dedoussis, George, Dominiczak, Anna F, Doney, Alex SF, Ellinor, Patrick T, Eppinga, Ruben N, Felix, Stephan B, Guo, Xiuqing, Hagemeijer, Yanick, Hansen, Torben, Harris, Tamara B, Heckbert, Susan R, Huang, Paul L, Hwang, Shih-Jen, Kähönen, Mika, Kanters, Jørgen K, Kolcic, Ivana, Launer, Lenore J, Li, Man, Yao, Jie, Linneberg, Allan, Liu, Simin, Macfarlane, Peter W, Mangino, Massimo, Morris, Andrew D, Mulas, Antonella, Murray, Alison D, Nelson, Christopher P, Orrú, Marco, Padmanabhan, Sandosh, Peters, Annette, Porteous, David J, Poulter, Neil, Psaty, Bruce M, Qi, Lihong, Raitakari, Olli T, Rivadeneira, Fernando, Roselli, Carolina, Rudan, Igor, Sattar, Naveed, Sever, Peter, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Timothy D, Stanton, Alice V, Stirrups, Kathleen E, Taylor, Kent D, Tobin, Martin D, Uitterlinden, André, Vaartjes, Ilonca, Hoes, Arno W, van der Meer, Peter, Völker, Uwe, Waldenberger, Melanie, Xie, Zhijun, Zoledziewska, Magdalena, Tinker, Andrew, Polasek, Ozren, Rosand, Jonathan, Jamshidi, Yalda, van Duijn, Cornelia M, Zeggini, Eleftheria, Jukema, J Wouter, Asselbergs, Folkert W, Samani, Nilesh J, and Lehtimäki, Terho

Subjects
Biological Sciences, Genetics, Human Genome, Biotechnology, Heart Disease, Prevention, Cardiovascular, Stem Cell Research, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Adult, Alleles, Exome, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Heart Rate, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Risk Factors, White People, Medical and Health Sciences, Genetics & Heredity
Abstract

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.

Published
2017

69. Tunable and low-loss correlated plasmons in Mott-like insulating oxides.

Author

Asmara, Teguh Citra, Wan, Dongyang, Zhao, Yongliang, Majidi, Muhammad Aziz, Nelson, Christopher T, Scott, Mary C, Cai, Yao, Yan, Bixing, Schmidt, Daniel, Yang, Ming, Zhu, Tao, Trevisanutto, Paolo E, Motapothula, Mallikarjuna R, Feng, Yuan Ping, Breese, Mark BH, Sherburne, Matthew, Asta, Mark, Minor, Andrew, Venkatesan, T, and Rusydi, Andrivo

Abstract

Plasmonics has attracted tremendous interests for its ability to confine light into subwavelength dimensions, creating novel devices with unprecedented functionalities. New plasmonic materials are actively being searched, especially those with tunable plasmons and low loss in the visible-ultraviolet range. Such plasmons commonly occur in metals, but many metals have high plasmonic loss in the optical range, a main issue in current plasmonic research. Here, we discover an anomalous form of tunable correlated plasmons in a Mott-like insulating oxide from the Sr1-xNb1-yO3+δ family. These correlated plasmons have multiple plasmon frequencies and low loss in the visible-ultraviolet range. Supported by theoretical calculations, these plasmons arise from the nanometre-spaced confinement of extra oxygen planes that enhances the unscreened Coulomb interactions among charges. The correlated plasmons are tunable: they diminish as extra oxygen plane density or film thickness decreases. Our results open a path for plasmonics research in previously untapped insulating and strongly-correlated materials.

Published
2017

70. Large polarization gradients and temperature-stable responses in compositionally-graded ferroelectrics.

Author

Damodaran, Anoop R, Pandya, Shishir, Qi, Yubo, Hsu, Shang-Lin, Liu, Shi, Nelson, Christopher, Dasgupta, Arvind, Ercius, Peter, Ophus, Colin, Dedon, Liv R, Agar, Josh C, Lu, Hongling, Zhang, Jialan, Minor, Andrew M, Rappe, Andrew M, and Martin, Lane W

Abstract

A range of modern applications require large and tunable dielectric, piezoelectric or pyroelectric response of ferroelectrics. Such effects are intimately connected to the nature of polarization and how it responds to externally applied stimuli. Ferroelectric susceptibilities are, in general, strongly temperature dependent, diminishing rapidly as one transitions away from the ferroelectric phase transition (TC). In turn, researchers seek new routes to manipulate polarization to simultaneously enhance susceptibilities and broaden operational temperature ranges. Here, we demonstrate such a capability by creating composition and strain gradients in Ba1-xSrxTiO3 films which result in spatial polarization gradients as large as 35 μC cm-2 across a 150 nm thick film. These polarization gradients allow for large dielectric permittivity with low loss (ɛr≈775, tan δ

Published
2017

71. Stability of Polar Vortex Lattice in Ferroelectric Superlattices

Author

Hong, Zijian, Damodaran, Anoop R, Xue, Fei, Hsu, Shang-Lin, Britson, Jason, Yadav, Ajay K, Nelson, Christopher T, Wang, Jian-Jun, Scott, James F, Martin, Lane W, Ramesh, Ramamoorthy, and Chen, Long-Qing

Subjects
Physical Sciences, Quantum Physics, Chemical Sciences, Macromolecular and Materials Chemistry, Ferroelectric superlattices, ultrafine polar vortex, geometric length scale, phase-field simulations, topological structures by design, Nanoscience & Nanotechnology
Abstract

A novel mesoscale state comprising of an ordered polar vortex lattice has been demonstrated in ferroelectric superlattices of PbTiO3/SrTiO3. Here, we employ phase-field simulations, analytical theory, and experimental observations to evaluate thermodynamic conditions and geometric length scales that are critical for the formation of such exotic vortex states. We show that the stability of these vortex lattices involves an intimate competition between long-range electrostatic, long-range elastic, and short-range polarization gradient-related interactions leading to both an upper and a lower bound to the length scale at which these states can be observed. We found that the critical length is related to the intrinsic domain wall width, which could serve as a simple intuitive design rule for the discovery of novel ultrafine topological structures in ferroic systems.

Published
2017

72. Advancing Evidence-Based Public Health Policy: How Core Component Thinking Can Illuminate the Multilevel Nature of Public Health Policy

Author

Puddy, Richard W., Kelly, Megan A., Nelson, Christopher, Ntazinda, Alexandra H., Siddiqi, Sameer, Hall, Diane, Murray, Christian T., and Kucik, James E.

Abstract

A growing body of literature uses the concept of core components to better understand small-scale programmatic interventions. Instead of interventions being viewed as unitary “black boxes,” interventions are viewed as configurations of core components, which are the parts of interventions that carry their causal potential and therefore need to be reproduced with fidelity to produce the intended effect. To date, the concept of core components has not been as widely applied to public health policy interventions as it has to programmatic interventions. The purpose of this topical review is to familiarize public health practitioners and policy makers with the concept of core components as applied to public health policy interventions. Raising the profile of core component thinking can foster mindful adaptation and implementation of public health policy interventions while encouraging further research to enhance the supporting evidence base. We present 3 types of multilevel interactions in which the core components of a public health policy intervention produce effects at the population level by (1) seeking to directly affect individual behavior, (2) facilitating adoption of programmatic interventions by intermediaries, and (3) encouraging intermediaries to take action that can shape changes in upstream drivers of population health. Changing the unit of analysis from whole policies to core components can provide a basis for understanding how policies work and for facilitating novel evidence-generating strategies and rapid evidence reviews that can inform future adaptation efforts.

Published
2024
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74. KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference

Author

Schumann, Gunter, Liu, Chunyu, O'Reilly, Paul, Gao, He, Song, Parkyong, Xu, Bing, Ruggeri, Barbara, Amin, Najaf, Jia, Tianye, Preis, Sarah, Segura Lepe, Marcelo, Akira, Shizuo, Barbieri, Caterina, Baumeister, Sebastian, Cauchi, Stephane, Clarke, Toni-Kim, Enroth, Stefan, Fischer, Krista, Hällfors, Jenni, Harris, Sarah E, Hieber, Saskia, Hofer, Edith, Hottenga, Jouke-Jan, Johansson, Åsa, Joshi, Peter K, Kaartinen, Niina, Laitinen, Jaana, Lemaitre, Rozenn, Loukola, Anu, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Mbarek, Hamdi, Milaneschi, Yuri, Moayyeri, Alireza, Mukamal, Kenneth, Nelson, Christopher, Nettleton, Jennifer, Partinen, Eemil, Rawal, Rajesh, Robino, Antonietta, Rose, Lynda, Sala, Cinzia, Satoh, Takashi, Schmidt, Reinhold, Schraut, Katharina, Scott, Robert, Smith, Albert Vernon, Starr, John M, Teumer, Alexander, Trompet, Stella, Uitterlinden, André G, Venturini, Cristina, Vergnaud, Anne-Claire, Verweij, Niek, Vitart, Veronique, Vuckovic, Dragana, Wedenoja, Juho, Yengo, Loic, Yu, Bing, Zhang, Weihua, Zhao, Jing Hua, Boomsma, Dorret I, Chambers, John, Chasman, Daniel I, Daniela, Toniolo, de Geus, Eco, Deary, Ian, Eriksson, Johan G, Esko, Tõnu, Eulenburg, Volker, Franco, Oscar H, Froguel, Philippe, Gieger, Christian, Grabe, Hans J, Gudnason, Vilmundur, Gyllensten, Ulf, Harris, Tamara B, Hartikainen, Anna-Liisa, Heath, Andrew C, Hocking, Lynne, Hofman, Albert, Huth, Cornelia, Jarvelin, Marjo-Riitta, Jukema, J Wouter, Kaprio, Jaakko, Kooner, Jaspal S, Kutalik, Zoltan, Lahti, Jari, Langenberg, Claudia, Lehtimäki, Terho, Liu, Yongmei, Madden, Pamela AF, Martin, Nicholas, Morrison, Alanna, Penninx, Brenda, Pirastu, Nicola, Psaty, Bruce, and Raitakari, Olli

Subjects
Underage Drinking, Genetics, Alcoholism, Alcohol Use and Health, Neurosciences, Substance Misuse, Pediatric, Underpinning research, 1.1 Normal biological development and functioning, Stroke, Cardiovascular, Cancer, Oral and gastrointestinal, Good Health and Well Being, Alcohol Drinking, Animals, Behavior, Animal, Brain, Emotions, Female, Fibroblast Growth Factors, Genome-Wide Association Study, Humans, Klotho Proteins, Liver, Male, Membrane Proteins, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Polymorphism, Single Nucleotide, alcohol consumption, human, beta-Klotho, FGF21, mouse model, β-Klotho
Abstract

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10-12). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.

Published
2016

75. Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila

Author

Nelson, Christopher S, Beck, Jennifer N, Wilson, Kenneth A, Pilcher, Elijah R, Kapahi, Pankaj, and Brem, Rachel B

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Aging, Biotechnology, Nutrition, Aetiology, 2.1 Biological and endogenous factors, Animals, Drosophila, Drosophila Proteins, Energy Metabolism, Female, Genetic Association Studies, Genetic Variation, Genotype, Huntingtin Protein, Longevity, Nutritional Physiological Phenomena, Phenotype, Quantitative Trait, Heritable, GWAS, Obesity, Dietary restriction, Information and Computing Sciences, Medical and Health Sciences, Bioinformatics, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundObesity-related diseases are major contributors to morbidity and mortality in the developed world. Molecular diagnostics and targets of therapies to combat nutritional imbalance are urgently needed in the clinic. Invertebrate animals have been a cornerstone of basic research efforts to dissect the genetics of metabolism and nutrient response. We set out to use fruit flies reared on restricted and nutrient-rich diets to identify genes associated with starvation resistance, body mass and composition, in a survey of genetic variation across the Drosophila Genetic Reference Panel (DGRP).ResultsWe measured starvation resistance, body weight and composition in DGRP lines on each of two diets and used several association mapping strategies to harness this panel of phenotypes for molecular insights. We tested DNA sequence variants for a relationship with single metabolic traits and with multiple traits at once, using a scheme for cross-phenotype association mapping; we focused our association tests on homologs of human disease genes and common polymorphisms; and we tested for gene-by-diet interactions. The results revealed gene and gene-by-diet associations between 17 variants and body mass, whole-body triglyceride and glucose content, or starvation resistance. Focused molecular experiments validated the role in body mass of an uncharacterized gene, CG43921 (which we rename heavyweight), and previously unknown functions for the diacylglycerol kinase rdgA, the huntingtin homolog htt, and the ceramide synthase schlank in nutrient-dependent body mass, starvation resistance, and lifespan.ConclusionsOur findings implicate a wealth of gene candidates in fly metabolism and nutrient response, and ascribe novel functions to htt, rdgA, hwt and schlank.

Published
2016

76. Abstract 12681: GWAS Meta-Analysis in SCAD, a Women Predominant Ischemic Heart Disease, Reveals Common Variants and Genes Related to Artery Integrity and Tissue-Mediated Coagulation

Author

Adlam, David, BERRANDOU, Takiy E, Georges, Adrien, Nelson, Christopher P, Giannoulatou, Eleni, Ma, Lijiang, Blencowe, Montgomory, Turley, Tamiel, Yang, Min-Lee, Iismaa, Siiri, Tarr, Ingrid, Muller, David, Hesselson, Stephanie, Junday, Keerat, Fatkin, Diane, COMBARET, Nicolas, Saw, Jacqueline, Webb, Tom, Tweet, Marysia, Hayes, Sharonne N, Xia, Yang, Ganesh, Santhi, Olson, Timothy M, Kovacic, Jason C, Graham, Robert M, Samani, Nilesh J, and Bouatia-Naji, Nabila

Published
2022
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77. Large-Scale Analysis of the Association between Air Pollutants and Leucocyte Telomere Length in the UK Biobank

Author

Bountziouka, Vasiliki, Hansell, Anita L., Nelson, Christopher P., Codd, Veryan, and Sainani, Nilesh J.

Subjects
Telomeres -- Health aspects -- Physiological aspects, Air pollution -- Health aspects -- Physiological aspects, Leukocytes -- Physiological aspects -- Health aspects, Environmental issues, Health
Abstract

Introduction Shorter telomere length (TL) and air pollution are both associated with higher risk of aging-related diseases. (1,2) Oxidative stress may mediate the adverse effects of air pollution and also [...]

Published
2023
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78. Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia

Author

Ojha, Juhi, Codd, Veryan, Nelson, Christopher P, Samani, Nilesh J, Smirnov, Ivan V, Madsen, Nils R, Hansen, Helen M, de Smith, Adam J, Bracci, Paige M, Wiencke, John K, Wrensch, Margaret R, Wiemels, Joseph L, and Walsh, Kyle M

Subjects
Biomedical and Clinical Sciences, Prevention, Human Genome, Genetics, Clinical Research, Lymphoma, Cancer, Rare Diseases, Hematology, Adult, Aged, Biomarkers, Tumor, Case-Control Studies, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Leukocytes, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Telomere Homeostasis, ENGAGE Consortium Telomere Group, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundChronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Shorter mean telomere length in leukemic cells has been associated with more aggressive disease. Germline polymorphisms in telomere maintenance genes affect telomere length and may contribute to CLL susceptibility.MethodsWe collected genome-wide data from two groups of patients with CLL (N = 273) and two control populations (N = 5,725). In ancestry-adjusted case-control comparisons, we analyzed eight SNPs in genes definitively associated with inter-individual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208, and RTEL1 RESULTS: Three of the eight LTL-associated SNPs were associated with CLL risk at P < 0.05, including those near: TERC [OR, 1.46; 95% confidence interval (CI), 1.15-1.86; P = 1.8 × 10(-3)], TERT (OR = 1.23; 95% CI, 1.02-1.48; P = 0.030), and OBFC1 (OR, 1.36; 95% CI, 1.08-1.71; P = 9.6 × 10(-3)). Using a weighted linear combination of the eight LTL-associated SNPs, we observed that CLL patients were predisposed to longer LTL than controls in both case-control sets (P = 9.4 × 10(-4) and 0.032, respectively). CLL risk increased monotonically with increasing quintiles of the weighted linear combination.ConclusionsGenetic variants in TERC, TERT, and OBFC1 are associated with both longer LTL and increased CLL risk. Because the human CST complex competes with shelterin for telomeric DNA, future work should explore the role of OBFC1 and other CST complex genes in leukemogenesis.ImpactA genetic predisposition to longer telomere length is associated with an increased risk of CLL, suggesting that the role of telomere length in CLL etiology may be distinct from its role in disease progression. Cancer Epidemiol Biomarkers Prev; 25(7); 1043-9. ©2016 AACR.

Published
2016

79. Identifying Novel Gene Variants in Coronary Artery Disease and Shared Genes With Several Cardiovascular Risk Factors.

Author

LeBlanc, Marissa, Zuber, Verena, Andreassen, Bettina Kulle, Witoelar, Aree, Zeng, Lingyao, Bettella, Francesco, Wang, Yunpeng, McEvoy, Linda K, Thompson, Wesley K, Schork, Andrew J, Reppe, Sjur, Barrett-Connor, Elizabeth, Ligthart, Symen, Dehghan, Abbas, Gautvik, Kaare M, Nelson, Christopher P, Schunkert, Heribert, Samani, Nilesh J, CARDIoGRAM Consortium, Ridker, Paul M, Chasman, Daniel I, Aukrust, Pål, Djurovic, Srdjan, Frigessi, Arnoldo, Desikan, Rahul S, Dale, Anders M, and Andreassen, Ole A

Subjects
CARDIoGRAM Consortium, Humans, Cardiovascular Diseases, Genetic Predisposition to Disease, Risk Factors, Cohort Studies, Prospective Studies, Female, Coronary Artery Disease, Genetic Variation, Genome-Wide Association Study, Women’s Genome Health Study, coronary artery disease, coronary heart disease, genetic pleiotropy, genome-wide association study, lipids, molecular epidemiology, myocardial infarction, Nutrition, Diabetes, Atherosclerosis, Prevention, Heart Disease, Aging, Biotechnology, Cardiovascular, Heart Disease - Coronary Heart Disease, Genetics, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Good Health and Well Being, Women's Genome Health Study, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract

RationaleCoronary artery disease (CAD) is a critical determinant of morbidity and mortality. Previous studies have identified several cardiovascular disease risk factors, which may partly arise from a shared genetic basis with CAD, and thus be useful for discovery of CAD genes.ObjectiveWe aimed to improve discovery of CAD genes and inform the pathogenic relationship between CAD and several cardiovascular disease risk factors using a shared polygenic signal-informed statistical framework.Methods and resultsUsing genome-wide association studies summary statistics and shared polygenic pleiotropy-informed conditional and conjunctional false discovery rate methodology, we systematically investigated genetic overlap between CAD and 8 traits related to cardiovascular disease risk factors: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, type 2 diabetes mellitus, C-reactive protein, body mass index, systolic blood pressure, and type 1 diabetes mellitus. We found significant enrichment of single-nucleotide polymorphisms associated with CAD as a function of their association with low-density lipoprotein, high-density lipoprotein, triglycerides, type 2 diabetes mellitus, C-reactive protein, body mass index, systolic blood pressure, and type 1 diabetes mellitus. Applying the conditional false discovery rate method to the enriched phenotypes, we identified 67 novel loci associated with CAD (overall conditional false discovery rate

Published
2016

80. On trace-convex noncommutative polynomials

Author

Klep, Igor, McCullough, Scott A., and Nelson, Christopher S.

Subjects
Mathematics - Operator Algebras, Mathematics - Functional Analysis, Primary: 13J30, 14A22, 46L07, Secondary: 16S10, 14P10, 47Lxx, 16Z05
Abstract

To each real continuous function f there is an associated trace function on real symmetric matrices Tr f. The classical Klein lemma states that f is convex if and only if Tr f is convex. In this note we present an algebraic strengthening of this lemma for univariate polynomials f: Tr f is convex if and only if the noncommutative second directional derivative of f is a sum of hermitian squares and commutators in a free algebra. We also give a localized version of this result., Comment: 17 pages, includes table of contents

Published
2014
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81. A Multi-Stage Supply Chain Network Optimization Using Genetic Algorithms

Author

Dzupire, Nelson Christopher and Nkansah-Gyekye, Yaw

Subjects
Mathematics - Optimization and Control, Computer Science - Neural and Evolutionary Computing
Abstract

In today's global business market place, individual firms no longer compete as independent entities with unique brand names but as integral part of supply chain links. Key to success of any business is satisfying customer's demands on time which may result in cost reductions and increase in service level. In supply chain networks decisions are made with uncertainty about product's demands, costs, prices, lead times, quality in a competitive and collaborative environment. If poor decisions are made, they may lead to excess inventories that are costly or to insufficient inventory that cannot meet customer's demands. In this work we developed a bi-objective model that minimizes system wide costs of the supply chain and delays on delivery of products to distribution centers for a three echelon supply chain. Picking a set of Pareto front for multi-objective optimization problems require robust and efficient methods that can search an entire space. We used evolutionary algorithms to find the set of Pareto fronts which have proved to be effective in finding the entire set of Pareto fronts., Comment: 12 pages, 4 figures

Published
2014

83. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

Author

Walsh, Kyle M, Codd, Veryan, Rice, Terri, Nelson, Christopher P, Smirnov, Ivan V, McCoy, Lucie S, Hansen, Helen M, Elhauge, Edward, Ojha, Juhi, Francis, Stephen S, Madsen, Nils R, Bracci, Paige M, Pico, Alexander R, Molinaro, Annette M, Tihan, Tarik, Berger, Mitchel S, Chang, Susan M, Prados, Michael D, Jenkins, Robert B, Wiemels, Joseph L, Group, ENGAGE Consortium Telomere, Samani, Nilesh J, Wiencke, John K, and Wrensch, Margaret R

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Brain Cancer, Cancer, Rare Diseases, Brain Disorders, Genetics, Prevention, Cancer Genomics, Neurosciences, 2.1 Biological and endogenous factors, Generic health relevance, Adult, Brain Neoplasms, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Glioma, Humans, Leukocytes, Male, Models, Statistical, Polymorphism, Single Nucleotide, Risk Factors, Telomere, single nucleotide polymorphism, telomerase, telomere, CST complex, glioma, ENGAGE Consortium Telomere Group, Oncology and carcinogenesis
Abstract

Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82x10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48x10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83x10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis.

Published
2015

85. Cas9-specific immune responses compromise local and systemic AAV CRISPR therapy in multiple dystrophic canine models

Author

Hakim, Chady H., Kumar, Sandeep R. P., Pérez-López, Dennis O., Wasala, Nalinda B., Zhang, Dong, Yue, Yongping, Teixeira, James, Pan, Xiufang, Zhang, Keqing, Million, Emily D., Nelson, Christopher E., Metzger, Samantha, Han, Jin, Louderman, Jacqueline A., Schmidt, Florian, Feng, Feng, Grimm, Dirk, Smith, Bruce F., Yao, Gang, Yang, N. Nora, Gersbach, Charles A., Chen, Shi-jie, Herzog, Roland W., and Duan, Dongsheng

Published
2021
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86. Oriented Growth of Gold Nanowires on MoS2

Author

Kiriya, Daisuke, Zhou, Yuzhi, Nelson, Christopher, Hettick, Mark, Madhvapathy, Surabhi Rao, Chen, Kevin, Zhao, Peida, Tosun, Mahmut, Minor, Andrew M, Chrzan, Daryl C, and Javey, Ali

Subjects
field effect transistors, nanowires, transition metal dichalcogenides, Physical Sciences, Chemical Sciences, Engineering, Materials
Abstract

Layered 2D materials serve as a new class of substrates for templated synthesis of various nanomaterials even with highly dissimilar crystal structures; thus overcoming the lattice constraints of conventional epitaxial processes. Here, molybdenum disulfide (MoS2) is used as a prototypical model substrate for oriented growth of in-plane Au nanowires (NWs) despite the nearly 8% lattice mismatch between MoS2 and Au. Au NWs on the MoS2 surface are oriented along three symmetrically equivalent directions within the substrate arising from the strong Au-S binding that templates the oriented growth. The kinetics of the growth process are explored through experiments and modeling. Strong charge transfer is observed between Au NWs and MoS2, resulting in degenerate p-doping of MoS2.

Published
2015

87. Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel Associations Between Key Biological Processes and Coronary Artery Disease

Author

Ghosh, Sujoy, Vivar, Juan, Nelson, Christopher P, Willenborg, Christina, Segrè, Ayellet V, Mäkinen, Ville-Petteri, Nikpay, Majid, Erdmann, Jeannette, Blankenberg, Stefan, O'Donnell, Christopher, März, Winfried, Laaksonen, Reijo, Stewart, Alexandre FR, Epstein, Stephen E, Shah, Svati H, Granger, Christopher B, Hazen, Stanley L, Kathiresan, Sekar, Reilly, Muredach P, Yang, Xia, Quertermous, Thomas, Samani, Nilesh J, Schunkert, Heribert, Assimes, Themistocles L, and McPherson, Ruth

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Heart Disease - Coronary Heart Disease, Cardiovascular, Genetics, Human Genome, Atherosclerosis, Heart Disease, Aetiology, 2.1 Biological and endogenous factors, Underpinning research, 1.1 Normal biological development and functioning, Coronary Artery Disease, Genome-Wide Association Study, Humans, coronary artery disease, pathway analysis, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

ObjectiveGenome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks.Approaches and resultsUsing pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11 089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15 502 cases/55 730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication P

Published
2015

88. Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.

Author

Horikoshi, Momoko, Mӓgi, Reedik, van de Bunt, Martijn, Surakka, Ida, Sarin, Antti-Pekka, Mahajan, Anubha, Marullo, Letizia, Thorleifsson, Gudmar, Hӓgg, Sara, Hottenga, Jouke-Jan, Ladenvall, Claes, Ried, Janina S, Winkler, Thomas W, Willems, Sara M, Pervjakova, Natalia, Esko, Tõnu, Beekman, Marian, Nelson, Christopher P, Willenborg, Christina, Wiltshire, Steven, Ferreira, Teresa, Fernandez, Juan, Gaulton, Kyle J, Steinthorsdottir, Valgerdur, Hamsten, Anders, Magnusson, Patrik KE, Willemsen, Gonneke, Milaneschi, Yuri, Robertson, Neil R, Groves, Christopher J, Bennett, Amanda J, Lehtimӓki, Terho, Viikari, Jorma S, Rung, Johan, Lyssenko, Valeriya, Perola, Markus, Heid, Iris M, Herder, Christian, Grallert, Harald, Müller-Nurasyid, Martina, Roden, Michael, Hypponen, Elina, Isaacs, Aaron, van Leeuwen, Elisabeth M, Karssen, Lennart C, Mihailov, Evelin, Houwing-Duistermaat, Jeanine J, de Craen, Anton JM, Deelen, Joris, Havulinna, Aki S, Blades, Matthew, Hengstenberg, Christian, Erdmann, Jeanette, Schunkert, Heribert, Kaprio, Jaakko, Tobin, Martin D, Samani, Nilesh J, Lind, Lars, Salomaa, Veikko, Lindgren, Cecilia M, Slagboom, P Eline, Metspalu, Andres, van Duijn, Cornelia M, Eriksson, Johan G, Peters, Annette, Gieger, Christian, Jula, Antti, Groop, Leif, Raitakari, Olli T, Power, Chris, Penninx, Brenda WJH, de Geus, Eco, Smit, Johannes H, Boomsma, Dorret I, Pedersen, Nancy L, Ingelsson, Erik, Thorsteinsdottir, Unnur, Stefansson, Kari, Ripatti, Samuli, Prokopenko, Inga, McCarthy, Mark I, Morris, Andrew P, and ENGAGE Consortium

Subjects
ENGAGE Consortium, Humans, Obesity, Genetic Predisposition to Disease, Glucose-6-Phosphatase, Protein-Serine-Threonine Kinases, Thrombospondins, Body Mass Index, Chromosome Mapping, Glycemic Index, Gene Frequency, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Germinal Center Kinases, Polymorphism, Single Nucleotide, Genetics, Developmental Biology
Abstract

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.

Published
2015

89. Cumulative effects of common genetic variants on risk of sudden cardiac death

Author

Huertas-Vazquez, Adriana, Nelson, Christopher P, Sinsheimer, Janet S, Reinier, Kyndaron, Uy-Evanado, Audrey, Teodorescu, Carmen, Ayala, Jo, Hall, Alistair S, Gunson, Karen, Jui, Jonathan, Samani, Nilesh J, and Chugh, Sumeet S

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Prevention, Cardiovascular, Human Genome, Heart Disease, Genetics, Heart Disease - Coronary Heart Disease, Hematology, Aetiology, 2.1 Biological and endogenous factors, Sudden cardiac death, Coronary artery disease, coronary artery disease, genetics, sudden cardiac death, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

BackgroundGenome-wide association studies and candidate-gene based approaches have identified multiple common variants associated with increased risk of sudden cardiac death (SCD). However, the independent contribution of these individual loci to disease risk is modest.ObjectiveTo investigate the cumulative effects of genetic variants previously associated with SCD risk.MethodsA total of 966 SCD cases from the Oregon-Sudden Unexpected Death Study and 1,926 coronary artery disease controls from the Wellcome Trust Case-Control Consortium were investigated. We generated genetic risk scores (GRS) for each trait composed of variants previously associated with SCD or with abnormalities in specific electrocardiographic traits such as QRS duration, QTc interval and heart rate. GRSs were calculated using a weighted approach based on the number of risk alleles weighted by the beta coefficients derived from the original studies. We also compared the highest and lowest quintiles for the GRS composed of SCD SNPs.ResultsIncreased cumulative risk was observed for a GRS composed of 14 SCD-SNPs (OR=1.17 [1.05-1.29], P = 0.002). The risk for SCD was 1.5 fold higher in the highest quintile when compared to the lowest quintile (OR = 1.46[1.11-1.92]). We did not observe significant associations with SCD for SNPs that determine electrocardiographic traits.ConclusionsA modest but significant effect on SCD risk was identified for a GRS composed of 14 previously associated SCD SNPs. While next generation sequencing methodology will continue to identify additional novel variants, these findings represent proof of concept for the additive effects of gene variants on SCD risk.

Published
2015

90. Noncommutative polynomials nonnegative on a variety intersect a convex set

Author

Helton, J. William, Klep, Igor, and Nelson, Christopher S.

Subjects
Mathematics - Functional Analysis, Mathematics - Rings and Algebras, Primary: 13J30, 14A22, 46L07, Secondary: 16S10, 47Lxx, 16Z05, 90C22
Abstract

By a result of Helton and McCullough, open bounded convex free semialgebraic sets are exactly open (matricial) solution sets D_L of a linear matrix inequality (LMI) L(X)>0. This paper gives a precise algebraic certificate for a polynomial being nonnegative on a convex semialgebraic set intersect a variety, a so-called "Perfect" Positivstellensatz. For example, given a generic convex free semialgebraic set D_L we determine all "(strong sense) defining polynomials" p for D_L. This follows from our general result for a given linear pencil L and a finite set I of rows of polynomials. A matrix polynomial p is positive where L is positive and I vanishes if and only if p has a weighted sum of squares representation module the "L-real radical" of I. In such a representation the degrees of the polynomials appearing depend in a very tame way only on the degree of p and the degrees of the elements of I. Further, this paper gives an efficient algorithm for computing the L-real radical of I. Our Positivstellensatz has a number of additional consequences which are presented., Comment: 69 pages, includes a table of contents

Published
2013
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91. A Real Nullstellensatz for Matrices of Non-Commutative Polynomials

Author

Nelson, Christopher S.

Subjects
Mathematics - Operator Algebras
Abstract

This article extends the classical Real Nullstellensatz to matrices of polynomials in a free $\ast$-algebra $\RR\axs$ with $x=(x_1, \ldots, x_n)$. This result is a generalization of a result of Cimpri\vc, Helton, McCullough, and the author. In the free left $\RR\axs$-module $\RR^{1 \times \ell}\axs$ we introduce notions of the (noncommutative) zero set of a left $\RR\axs$-submodule and of a real left $\RR\axs$-submodule. We prove that every element from $\RR^{1 \times \ell}\axs$ whose zero set contains the intersection of zero sets of elements from a finite subset $S \subset \RR^{1 \times \ell}\axs$ belongs to the smallest real left $\RR\axs$-submodule containing $S$. Using this, we derive a nullstellensatz for matrices of polynomials in $\RR\axs$. The other main contribution of this article is an efficient, implementable algorithm which for every finite subset $S \subset \RR^{1 \times \ell}\axs$ computes the smallest real left $\RR\axs$-submodule containing $S$. This algorithm terminates in a finite number of steps. By taking advantage of the rigid structure of $\RR\axs$, the algorithm presented here is an improvement upon the previously known algorithm for $\RR\axs$.

Published
2013

93. Real Nullstellensatze and *-ideals in *-algebras

Author

Cimpric, Jakob, Helton, J. William, McCullough, Scott, and Nelson, Christopher

Subjects
Mathematics - Functional Analysis, Mathematics - Rings and Algebras, 16W10, 16S10, 16Z05, 14P99, 14A22, 47Lxx, 13J30
Abstract

Let F denote either the real or complex field. An ideal I in the free *-algebra F in g freely noncommuting variables and their formal adjoints is a *-ideal if I = I*. When a real *-ideal has finite codimension, it satisfies a strong Nullstellensatz. Without the finite codimension assumption, there are examples of such ideals which do not satisfy, very liberally interpreted, any Nullstellensatz. A polynomial p in F is analytic if it is a polynomial in the variables {x} only; that is if p in F. As shown in this article, *-ideals generated by analytic polynomials do satisfy a natural Nullstellensatz and those generated by homogeneous analytic polynomials have a particularly simple description. The article also connects the results here for *-ideals to the literature on Nullstellensatz for left ideals in *-algebras generally and in F in particular. It also develops the concomitant general theory of *-ideals in general *-algebras.

Published
2013
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94. Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals

Author

Noordam, Raymond, Young, William J., Salman, Reem, Kanters, Jørgen K., van den Berg, Marten E., van Heemst, Diana, Lin, Henry J., Barreto, Sandhi Maria, Biggs, Mary L., Biino, Ginevra, Catamo, Eulalia, Concas, Maria Pina, Ding, Jun, Evans, Daniel S., Foco, Luisa, Grarup, Niels, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Mei, Hao, van der Most, Peter J., Müller-Nurasyid, Martina, Nelson, Christopher P., Qian, Yong, Repetto, Linda, Said, M. Abdullah, Shah, Nabi, Schramm, Katharina, Vidigal, Pedro G., Weiss, Stefan, Yao, Jie, Zilhao, Nuno R., Brody, Jennifer A., Braund, Peter S., Brumat, Marco, Campana, Eric, Christofidou, Paraskevi, Caulfield, Mark J., De Grandi, Alessandro, Dominiczak, Anna F., Doney, Alex S.F., Eiriksdottir, Gudny, Ellervik, Christina, Giatti, Luana, Gögele, Martin, Graff, Claus, Guo, Xiuqing, van der Harst, Pim, Joshi, Peter K., Kähönen, Mika, Kestenbaum, Bryan, Lima-Costa, Maria F., Linneberg, Allan, Maan, Arie C., Meitinger, Thomas, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Petersmann, Astrid, Sever, Peter, Sinner, Mortiz F., Shen, Xia, Stanton, Alice, Strauch, Konstantin, Soliman, Elsayed Z., Tarasov, Kirill V., Taylor, Kent D., Thio, Chris H.L., Uitterlinden, André G., Vaccargiu, Simona, Waldenberger, Melanie, Robino, Antonietta, Correa, Adolfo, Cucca, Francesco, Cummings, Steven R., Dörr, Marcus, Girotto, Giorgia, Gudnason, Vilmundur, Hansen, Torben, Heckbert, Susan R., Juhl, Christian R., Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Lotufo, Paulo A., Palmer, Colin N.A., Pirastu, Mario, Pramstaller, Peter P., Ribeiro, Antonio Luiz P., Rotter, Jerome I., Samani, Nilesh J., Snieder, Harold, Spector, Tim D., Stricker, Bruno H., Verweij, Niek, Wilson, James F., Wilson, James G., Jukema, J. Wouter, Tinker, Andrew, Newton-Cheh, Christopher H., Sotoodehnia, Nona, Mook-Kanamori, Dennis O., Munroe, Patricia B., and Warren, Helen R.

Published
2019
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95. Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection

Author

Motreff, Pascal, Belle, Loïc, Dupouy, Patrick, Barnay, Pierre, Meneveau, Nicolas, Gilard, Martine, Rioufol, Gilles, Range, Grégoire, Brunel, Philippe, Delarche, Nicolas, Filippi, Emmanuelle, Le Bivic, Louis, Harbaoui, Brahim, Benamer, Hakim, Cayla, Guillaume, Varenne, Olivier, Manzo-Silberman, Stephane Peggy, Silvain, Johanne, Spaulding, Christian, Caussin, Christophe, Gerbaud, Edouard, Valy, Yann, Koning, René, Lhermusier, Thibault, Champin, Stanislas, Salengro, Emmanuel, Fluttaz, Arnaud, Zabalawi, Amer, Cottin, Yves, Teiger, Emmanuel, Saint-Etienne, Christophe, Ducrocq, Grégory, Marliere, Stéphanie, Boiffard, Emmanuel, Aubry, Pierre, Georges, Jean Louis, Bresson, Didier, De Poli, Fabien, Karrillon, Gaëtan, Roule, Vincent, Bali, Laurent, Valla, Mathieu, Gerbay, Antoine, Houpe, David, Dubreuil, Olivier, Monnier, Arsène, Mayaud, Norbert, Manchuelle, Aurélie, Commeau, Philippe, Bedossa, Marc, Nikpay, Majid, Goel, Anuj, Won, Hong-Hee, Hall, Leanne M., Willenborg, Christina, Kanoni, Stavroula, Saleheen, Danish, Kyriakou, Theodosios, Nelson, Christopher P., Hopewell, Jemma C., Webb, Thomas R., Zeng, Lingyao, Dehghan, Abbas, Alver, Maris, Armasu, Sebastian M., Auro, Kirsi, Bjonnes, Andrew, Chasman, Daniel I., Chen, Shufeng, Ford, Ian, Franceschini, Nora, Gieger, Christian, Grace, Christopher, Gustafsson, Stefan, Huang, Jie, Hwang, Shih-Jen, Kim, Yun Kyoung, Kleber, Marcus E., Lau, King Wai, Lu, Xiangfeng, Lu, Yingchang, Lyytikäinen, Leo P., Mihailov, Evelin, Morrison, Alanna, Pervjakova, Natalia, Qu, Liming, Rose, Lynda M., Salfati, Elias, Saxena, Richa, Scholz, Markus, Smith, Albert V., Tikkanen, Emmi, Uitterlinden, Andre, Yang, Xueli, Zhang, Weihua, Zhao, Wei, de Andrade, Mariza, de Vries, Paul S., van Zuydam, Natalie R., Anand, Sonia S., Bertram, Lars, Beutner, Frank, Dedoussis, George, Frossard, Philippe, Gauguier, Dominique, Goodall, Alison H., Gottesman, Omri, Haber, Marc, Han, Bok-Ghee, Huang, Jianfeng, Jalilzadeh, Shapour, Kessler, Thorsten, König, Inke R., Lannfelt, Lars, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M., Lokki, Maisa, Magnusson, Patrik K., Mallick, Nadeem H., Mehra, Narinder, Meitinger, Thomas, Memon, Fazal-ur-Rehman, Morris, Andrew P., Nieminen, Markku S., Pedersen, Nancy L., Peters, Annette, Rallidis, Loukianos S., Rasheed, Asif, Samuel, Maria, Shah, Svati H., Sinisalo, Juha, Stirrups, Kathleen E., Trompet, Stella, Wang, Laiyuan, Zaman, Khan S., Ardissino, Diego, Boerwinkle, Eric, Borecki, Ingrid B., Bottinger, Erwin P., Buring, Julie E., Chambers, John C., Collins, Rory, Cupples, L Adrienne, Danesh, John, Demuth, Ilja, Elosua, Roberto, Epstein, Stephen E., Esko, Tõnu, Feitosa, Mary F., Franco, Oscar H., Franzosi, Maria Grazia, Granger, Christopher B., Gu, Dongfeng, Gudnason, Vilmundur, Hall, Alistair S., Hamsten, Anders, Harris, Tamara B., Hazen, Stanley L., Hengstenberg, Christian, Hofman, Albert, Ingelsson, Erik, Iribarren, Carlos, Jukema, J Wouter, Karhunen, Pekka J., Kim, Bong-Jo, Kooner, Jaspal S., Kullo, Iftikhar J., Lehtimäki, Terho, Loos, Ruth J., Melander, Olle, Metspalu, Andres, März, Winfried, Palmer, Colin N., Perola, Markus, Quertermous, Thomas, Rader, Daniel J., Ridker, Paul M., Ripatti, Samuli, Roberts, Robert, Salomaa, Veikko, Sanghera, Dharambir K., Schwartz, Stephen M., Seedorf, Udo, Stewart, Alexandre F., Stott, David J., Thiery, Joachim, Zalloua, Pierre A., O'Donnell, Christopher J., Reilly, Muredach P., Assimes, Themistocles L., Thompson, John R., Erdmann, Jeanette, Clarke, Robert, Watkins, Hugh, Kathiresan, Sekar, McPherson, Ruth, Deloukas, Panos, Schunkert, Heribert, Samani, Nilesh J., Farrall, Martin, Adlam, David, Olson, Timothy M., Combaret, Nicolas, Kovacic, Jason C., Iismaa, Siiri E., Al-Hussaini, Abtehale, O'Byrne, Megan M., Bouajila, Sara, Georges, Adrien, Mishra, Ketan, Braund, Peter S., d’Escamard, Valentina, Huang, Siying, Margaritis, Marios, Kadian-Dodov, Daniella, Welch, Catherine A., Mazurkiewicz, Stephani, Jeunemaitre, Xavier, Wong, Claire Mei Yi, Giannoulatou, Eleni, Sweeting, Michael, Muller, David, Wood, Alice, McGrath-Cadell, Lucy, Fatkin, Diane, Dunwoodie, Sally L., Harvey, Richard, Holloway, Cameron, Empana, Jean-Philippe, Jouven, Xavier, Olin, Jeffrey W., Gulati, Rajiv, Tweet, Marysia S., Hayes, Sharonne N., Graham, Robert M., and Bouatia-Naji, Nabila

Published
2019
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96. On real one-sided ideals in a free algebra

Author

Cimprič, Jakob, Helton, J. William, Klep, Igor, McCullough, Scott, and Nelson, Christopher

Subjects
Mathematics - Rings and Algebras, Mathematics - Algebraic Geometry, Mathematics - Functional Analysis, Primary 14P10, 08B20, Secondary 90C22, 16W10, 13J30
Abstract

In classical and real algebraic geometry there are several notions of the radical of an ideal I. There is the vanishing radical defined as the set of all real polynomials vanishing on the real zero set of I, and the real radical defined as the smallest real ideal containing I. By the real Nullstellensatz they coincide. This paper focuses on extensions of these to the free algebra R of noncommutative real polynomials in x=(x_1,...,x_g) and x^*=(x_1^*,...,x_g^*). We work with a natural notion of the (noncommutative real) zero set V(I) of a left ideal I in the free algebra. The vanishing radical of I is the set of all noncommutative polynomials p which vanish on V(I). In this paper our quest is to find classes of left ideals I which coincide with their vanishing radical. We completely succeed for monomial ideals and homogeneous principal ideals. We also present the case of principal univariate ideals with a degree two generator and find that it is very messy. Also we give an algorithm (running under NCAlgebra) which checks if a left ideal is radical or is not, and illustrate how one uses our implementation of it., Comment: v1: 31 pages; v2: 32 pages

Published
2012
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97. Noncommutative Harmonic and Subharmonic Polynomials and other Noncommutative Partial Differential Equations

Author

Nelson, Christopher

Subjects
Mathematics - Functional Analysis
Abstract

Solutions to Laplace's equation are called harmonic functions. Harmonic functions arise in many applications, such as physics and the theory of stochastic processes. Of interest classically are harmonic polynomials, which have a simple classification. Further, the work of Reznick, building on the work of others, namely Sylvester, Clifford, Rosanes, Gundelfinger, Cartan, Maass and Helgason, has led to a classification of all polynomial solutions to a differential equation of arising from a homogeneous polynomial over an algebraically closed field. The definition of harmonicity can be extended to the space of polynomials in free variables using the concept of a noncommutative Laplacian. Given a positive integer $\ell$, the $\ell$-Laplacian of a noncommutative (abbreviated NC) polynomial $p$ in the direction $h$ is defined to be $$ \lap_{\ell}[p,h] := \sum_{i=1}^g \frac{d^{\ell}}{dt^{\ell}} p(x_1,..., x_i + th,..., x_g).$$ A NC polynomial $p$ is said to be $\ell$-harmonic if $\lap_{\ell}[p,h] = 0$. When $\ell = 2$, then the $\ell$-Laplacian is simply called the Laplacian and a $\ell$-harmonic NC polynomial is simply called harmonic. More generally, the concept of a constant coefficient differential equation can be extended to the space of NC polynomials via the NC directional derivative. The main contribution of this paper is to classify the set of $\ell$-harmonic NC polynomials. The result is analogous to the classification of polynomial solutions to a differential equation of the form $q(\partial/\partial x_1, ..., \partial/\partial x_g)y = 0$ given by Reznick. Additionally, this thesis proves new results about NC "subharmonic" polynomials. This work extends results of Helton, McAllaster, and Hernandez on NC harmonic and subharmonic polynomials, which classified solutions for the $\ell = 2$ case in two noncommuting variables $x_1$ and $x_2$., Comment: arXiv admin note: text overlap with arXiv:0909.4884

Published
2012

99. A Non-commutative Real Nullstellensatz Corresponds to a Non-commutative Real Ideal; Algorithms

Author

Cimpric, Jaka, Helton, Bill, McCullough, Scott, and Nelson, Christopher

Subjects
Mathematics - Functional Analysis, Mathematics - Algebraic Geometry, 16W10, 16S10, 16Z05, 14P99, 14A22, 47Lxx, 13J30
Abstract

This article takes up the challenge of extending the classical Real Nullstellensatz of Dubois and Risler to left ideals in a *-algebra A. After introducing the notions of non-commutative zero sets and real ideals, we develop three themes related to our basic question: does an element p of A having zero set containing the intersection of zero sets of elements from a finite set S of A belong to the smallest real ideal containing S? Firstly, we construct some general theory which shows that if a canonical topological closure of certain objects are permitted, then the answer is yes, while at the purely algebraic level it is no. Secondly for every finite subset S of the free *-algebra R of polynomials in g indeterminates and their formal adjoints, we give an implementable algorithm which computes the smallest real ideal containing S and prove that the algorithm succeeds in a finite number of steps. Lastly we provide examples of noncommutative real ideals for which a purely algebraic non-commutative real Nullstellensatz holds. For instance, this includes the real (left) ideals generated by a finite sets S in the *-algebra of n by n matrices whose entries are polynomials in one-variable. Further, explicit sufficient conditions on a left ideal in R are given which cover all the examples of such ideals of which we are aware and significantly more., Comment: Improved results compared to earlier versions

Published
2011
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100. Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease.

Author

Mäkinen, Ville-Petteri, Civelek, Mete, Meng, Qingying, Zhang, Bin, Zhu, Jun, Levian, Candace, Huan, Tianxiao, Segrè, Ayellet V, Ghosh, Sujoy, Vivar, Juan, Nikpay, Majid, Stewart, Alexandre FR, Nelson, Christopher P, Willenborg, Christina, Erdmann, Jeanette, Blakenberg, Stefan, O'Donnell, Christopher J, März, Winfried, Laaksonen, Reijo, Epstein, Stephen E, Kathiresan, Sekar, Shah, Svati H, Hazen, Stanley L, Reilly, Muredach P, Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Consortium, Lusis, Aldons J, Samani, Nilesh J, Schunkert, Heribert, Quertermous, Thomas, McPherson, Ruth, Yang, Xia, and Assimes, Themistocles L

Subjects
Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Consortium, Animals, Humans, Mice, Genetic Predisposition to Disease, Genomics, Signal Transduction, Gene Expression Regulation, Gene Regulatory Networks, Coronary Artery Disease, Genome-Wide Association Study, Developmental Biology, Genetics
Abstract

The majority of the heritability of coronary artery disease (CAD) remains unexplained, despite recent successes of genome-wide association studies (GWAS) in identifying novel susceptibility loci. Integrating functional genomic data from a variety of sources with a large-scale meta-analysis of CAD GWAS may facilitate the identification of novel biological processes and genes involved in CAD, as well as clarify the causal relationships of established processes. Towards this end, we integrated 14 GWAS from the CARDIoGRAM Consortium and two additional GWAS from the Ottawa Heart Institute (25,491 cases and 66,819 controls) with 1) genetics of gene expression studies of CAD-relevant tissues in humans, 2) metabolic and signaling pathways from public databases, and 3) data-driven, tissue-specific gene networks from a multitude of human and mouse experiments. We not only detected CAD-associated gene networks of lipid metabolism, coagulation, immunity, and additional networks with no clear functional annotation, but also revealed key driver genes for each CAD network based on the topology of the gene regulatory networks. In particular, we found a gene network involved in antigen processing to be strongly associated with CAD. The key driver genes of this network included glyoxalase I (GLO1) and peptidylprolyl isomerase I (PPIL1), which we verified as regulatory by siRNA experiments in human aortic endothelial cells. Our results suggest genetic influences on a diverse set of both known and novel biological processes that contribute to CAD risk. The key driver genes for these networks highlight potential novel targets for further mechanistic studies and therapeutic interventions.

Published
2014

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