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252. Combating the effects of heat stress in dairy cows.

Author

Warren, Helen

Subjects
*DAIRY cattle, *PHYSIOLOGICAL effects of temperature, *CLIMATE change adaptation, *FEED utilization efficiency
Abstract

The article provides information on dealing with the effects of heat stress in dairy cows. Topic discussed include biological effects of heat stress, strategies for combating heat stress, and feed additives that can be considered for their ability to improve rumen function and immune response and to promote energy utilisation and feed conversion efficiency.

Published
2023

253. Mutations in IGSF10 cause self-limited delayed puberty

Author

Howard, Sasha, primary, Guasti, Leonardo, additional, Ruiz-Babot, Gerard, additional, Mancini, Alessandra, additional, David, Alessia, additional, Storr, Helen, additional, Metherell, Louise, additional, Cabrera, Claudia, additional, Warren, Helen, additional, Barnes, Michael, additional, Wehkalampi, Karoliina, additional, Gothilf, Yoav, additional, Andre, Valentina, additional, Cariboni, Anna, additional, and Dunkel, Leo, additional

Published
2015
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266. Causal Associations of Adiposity and Body Fat Distribution with Coronary Heart Disease, Stroke Subtypes and Type 2 Diabetes: A Mendelian Randomization Analysis.

Author

Dale, Caroline E., Fatemifar, Ghazaleh, Palmer, Tom M., White, Jon, Prieto-Merino, David, Zabaneh, Delilah, Engmann, Jorgen E. L., Shah, Tina, Wong, Andrew, Warren, Helen R., McLachlan, Stela, Trompet, Stella, Moldovan, Max, Morris, Richard W., Sofat, Reecha, Kumari, Meena, Hyppönen, Elina, Jefferis, Barbara J., Gaunt, Tom R., and Ben-Shlomo, Yoav

Published
2017
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267. A genome-wide interaction analysis of tricyclic/ tetracyclic antidepressants and RR and QT intervals: a pharmacogenomics study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.

Author

Noordam, Raymond, Sitlani, Colleen M., Avery, Christy L., Stewart, James D., Gogarten, Stephanie M., Wiggins, Kerri L., Trompet, Stella, Warren, Helen R., Fangui Sun, Evans, Daniel S., Xiaohui Li, Jin Li, Smith, Albert V., Bis, Joshua C., Brody, Jennifer A., Busch, Evan L., Caulfield, Mark J., Chen, Yii-Der I., Cummings, Steven R., and Cupples, L. Adrienne

Abstract

Background Increased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/tetracyclic antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals. Methods and results We conducted race/ethnicspecific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45 706; n=1417 TCA users), African (n=10 235; n=296 TCA users) and Hispanic/Latino (n=13 808; n=147 TCA users) ancestry, adjusted for clinical covariates. Among the populations of European ancestry, two genome-wide significant loci were identified for RR interval: rs6737205 in BRE (β=56.3, pinteraction=3.9e-9) and rs9830388 in UBE2E2 (β=25.2, pinteraction=1.7e-8). In Hispanic/Latino cohorts, rs2291477 in TGFBR3 significantly modified the association between TCAs and QT intervals (β=9.3, pinteraction=2.55e-8). In the metaanalyses of the other ethnicities, these loci either were excluded from the meta-analyses (as part of quality control), or their effects did not reach the level of nominal statistical significance (pinteraction>0.05). No new variants were identified in these ethnicities. No additional loci were identified after inverse-varianceweighted meta-analysis of the three ancestries. Conclusions Among Europeans, TCA interactions with variants in BRE and UBE2E2 were identified in relation to RR intervals. Among Hispanic/Latinos, variants in TGFBR3 modified the relation between TCAs and QT intervals. Future studies are required to confirm our results. [ABSTRACT FROM AUTHOR]

Published
2017
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268. How trace minerals impact a dairy cow's transition period: Trace mineral inclusions change during the dairy cow's transition period, when its productivity and health can be greatly affected by their presence or absence.

Author

WARREN, HELEN

Subjects
CATTLE parturition, TRACE elements, IMMUNE system, MICRONUTRIENTS, MAGNESIUM
Abstract

The article discusses impact of trace minerals on dairy cow's transition period. Topics discussed include impact of negative energy balance (NEB) on the immune system; role of trace minerals to reduce the availability of other minerals, such as magnesium (Mg) and phosphorus (P); and need to improve micronutrient supplementation during the transition to improve calving condition and reduce the time interval between calving and first service.

Published
2021

269. Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Author

Evangelou, Evangelos, Warren, Helen R., Mosen-Ansorena, David, Mifsud, Borbala, Pazoki, Raha, Gao, He, Ntritsos, Georgios, Dimou, Niki, Cabrera, Claudia P., Karaman, Ibrahim, Ng, Fu Liang, Evangelou, Marina, Witkowska, Katarzyna, Tzanis, Evan, Hellwege, Jacklyn N., Giri, Ayush, Velez Edwards, Digna R., Sun, Yan V., Cho, Kelly, Gaziano, J. Michael, Wilson, Peter W. F., Tsao, Philip S., Kovesdy, Csaba P., Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Debette, Stéphanie, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G., Jackson, Anne U., Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Prins, Bram Peter, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M., Zhao, Jing-Hua, Amouyel, Philippe, Connell, John, de Mutsert, Renée, Doney, Alex S. F., 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, Demirkale, Cumhur Yusuf, Dörr, Marcus, Ehret, Georg B., Elosua, Roberto, Enroth, Stefan, Erzurumluoglu, A. Mesut, 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, Jukema, J. Wouter, 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 C. M., Lin, Li, Lind, Lars, Lindgren, Cecilia M., Liu, YongMei, Loos, Ruth J. F., 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, Penninx, Brenda W. J. H., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Nguyen, Quang Tri, Raitakari, Olli T., Ren, Meixia, 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., Vergnaud, Anne-Claire, 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 M. M., Laakso, Markku, Lakatta, Edward G., Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O., Palmer, Colin N. A., 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, Hung, Adriana M., O’Donnell, Christopher J., Edwards, Todd L., Psaty, Bruce M., Tzoulaki, Ioanna, Barnes, Michael R., Wain, Louise V., Elliott, Paul, and Caulfield, Mark J.

Abstract

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

Published
2018
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270. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes

Author

Mahajan, Anubha, Wessel, Jennifer, Willems, Sara M., Zhao, Wei, Robertson, Neil R., Chu, Audrey Y., Gan, Wei, Kitajima, Hidetoshi, Taliun, Daniel, Rayner, N. William, Guo, Xiuqing, Lu, Yingchang, Li, Man, Jensen, Richard A., Hu, Yao, Huo, Shaofeng, Lohman, Kurt K., Zhang, Weihua, Cook, James P., Prins, Bram Peter, Flannick, Jason, Grarup, Niels, Trubetskoy, Vassily Vladimirovich, Kravic, Jasmina, Kim, Young Jin, Rybin, Denis V., Yaghootkar, Hanieh, Müller-Nurasyid, Martina, Meidtner, Karina, Li-Gao, Ruifang, Varga, Tibor V., Marten, Jonathan, Li, Jin, Smith, Albert Vernon, An, Ping, Ligthart, Symen, Gustafsson, Stefan, Malerba, Giovanni, Demirkan, Ayse, Tajes, Juan Fernandez, Steinthorsdottir, Valgerdur, Wuttke, Matthias, Lecoeur, Cécile, Preuss, Michael, Bielak, Lawrence F., Graff, Marielisa, Highland, Heather M., Justice, Anne E., Liu, Dajiang J., Marouli, Eirini, Peloso, Gina Marie, Warren, Helen R., Afaq, Saima, Afzal, Shoaib, Ahlqvist, Emma, Almgren, Peter, Amin, Najaf, Bang, Lia B., Bertoni, Alain G., Bombieri, Cristina, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A., Burtt, Noël P., Canouil, Mickaël, Chen, Yii-Der Ida, Cho, Yoon Shin, Christensen, Cramer, Eastwood, Sophie V., Eckardt, Kai-Uwe, Fischer, Krista, Gambaro, Giovanni, Giedraitis, Vilmantas, Grove, Megan L., de Haan, Hugoline G., Hackinger, Sophie, Hai, Yang, Han, Sohee, Tybjærg-Hansen, Anne, Hivert, Marie-France, Isomaa, Bo, Jäger, Susanne, Jørgensen, Marit E., Jørgensen, Torben, Käräjämäki, Annemari, Kim, Bong-Jo, Kim, Sung Soo, Koistinen, Heikki A., Kovacs, Peter, Kriebel, Jennifer, Kronenberg, Florian, Läll, Kristi, Lange, Leslie A., Lee, Jung-Jin, Lehne, Benjamin, Li, Huaixing, Lin, Keng-Hung, Linneberg, Allan, Liu, Ching-Ti, Liu, Jun, Loh, Marie, Mägi, Reedik, Mamakou, Vasiliki, McKean-Cowdin, Roberta, Nadkarni, Girish, Neville, Matt, Nielsen, Sune F., Ntalla, Ioanna, Peyser, Patricia A., Rathmann, Wolfgang, Rice, Kenneth, Rich, Stephen S., Rode, Line, Rolandsson, Olov, Schönherr, Sebastian, Selvin, Elizabeth, Small, Kerrin S., Stančáková, Alena, Surendran, Praveen, Taylor, Kent D., Teslovich, Tanya M., Thorand, Barbara, Thorleifsson, Gudmar, Tin, Adrienne, Tönjes, Anke, Varbo, Anette, Witte, Daniel R., Wood, Andrew R., Yajnik, Pranav, Yao, Jie, Yengo, Loïc, Young, Robin, Amouyel, Philippe, Boeing, Heiner, Boerwinkle, Eric, Bottinger, Erwin P., Chowdhury, Rajiv, Collins, Francis S., Dedoussis, George, Dehghan, Abbas, Deloukas, Panos, Ferrario, Marco M., Ferrières, Jean, Florez, Jose C., Frossard, Philippe, Gudnason, Vilmundur, Harris, Tamara B., Heckbert, Susan R., Howson, Joanna M. M., Ingelsson, Martin, Kathiresan, Sekar, Kee, Frank, Kuusisto, Johanna, Langenberg, Claudia, Launer, Lenore J., Lindgren, Cecilia M., Männistö, Satu, Meitinger, Thomas, Melander, Olle, Mohlke, Karen L., Moitry, Marie, Morris, Andrew D., Murray, Alison D., de Mutsert, Renée, Orho-Melander, Marju, Owen, Katharine R., Perola, Markus, Peters, Annette, Province, Michael A., Rasheed, Asif, Ridker, Paul M., Rivadineira, Fernando, Rosendaal, Frits R., Rosengren, Anders H., Salomaa, Veikko, Sheu, Wayne H.-H., Sladek, Rob, Smith, Blair H., Strauch, Konstantin, Uitterlinden, André G., Varma, Rohit, Willer, Cristen J., Blüher, Matthias, Butterworth, Adam S., Chambers, John Campbell, Chasman, Daniel I., Danesh, John, van Duijn, Cornelia, Dupuis, Josée, Franco, Oscar H., Franks, Paul W., Froguel, Philippe, Grallert, Harald, Groop, Leif, Han, Bok-Ghee, Hansen, Torben, Hattersley, Andrew T., Hayward, Caroline, Ingelsson, Erik, Kardia, Sharon L. R., Karpe, Fredrik, Kooner, Jaspal Singh, Köttgen, Anna, Kuulasmaa, Kari, Laakso, Markku, Lin, Xu, Lind, Lars, Liu, Yongmei, Loos, Ruth J. F., Marchini, Jonathan, Metspalu, Andres, Mook-Kanamori, Dennis, Nordestgaard, Børge G., Palmer, Colin N. A., Pankow, James S., Pedersen, Oluf, Psaty, Bruce M., Rauramaa, Rainer, Sattar, Naveed, Schulze, Matthias B., Soranzo, Nicole, Spector, Timothy D., Stefansson, Kari, Stumvoll, Michael, Thorsteinsdottir, Unnur, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Wareham, Nicholas J., Wilson, James G., Zeggini, Eleftheria, Scott, Robert A., Barroso, Inês, Frayling, Timothy M., Goodarzi, Mark O., Meigs, James B., Boehnke, Michael, Saleheen, Danish, Morris, Andrew P., Rotter, Jerome I., and McCarthy, Mark I.

Abstract

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P< 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.

Published
2018
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271. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D’Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian’an, Lubitz, Steven A., Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O’Connel, Jeffrey R., O’Donoghue, Michelle L., Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H.-H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J. F.

Abstract

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4Rand KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4Rmutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

Published
2018
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272. Exome-wide association study of plasma lipids in >300,000 individuals

Author

Liu, Dajiang J, Peloso, Gina M, Yu, Haojie, Butterworth, Adam S, Wang, Xiao, Mahajan, Anubha, Saleheen, Danish, Emdin, Connor, Alam, Dewan, Alves, Alexessander Couto, Amouyel, Philippe, Di Angelantonio, Emanuele, Arveiler, Dominique, Assimes, Themistocles L, Auer, Paul L, Baber, Usman, Ballantyne, Christie M, Bang, Lia E, Benn, Marianne, Bis, Joshua C, Boehnke, Michael, Boerwinkle, Eric, Bork-Jensen, Jette, Bottinger, Erwin P, Brandslund, Ivan, Brown, Morris, Busonero, Fabio, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Y Eugene, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Connell, John M, Cucca, Francesco, Cupples, L Adrienne, Damrauer, Scott M, Davies, Gail, Deary, Ian J, Dedoussis, George, Denny, Joshua C, Dominiczak, Anna, Dubé, Marie-Pierre, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Farmaki, Aliki-Eleni, Feitosa, Mary F, Ferrario, Marco, Ferrieres, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W, Frayling, Timothy M, Frikke-Schmidt, Ruth, Fritsche, Lars G, Frossard, Philippe, Fuster, Valentin, Ganesh, Santhi K, Gao, Wei, Garcia, Melissa E, Gieger, Christian, Giulianini, Franco, Goodarzi, Mark O, Grallert, Harald, Grarup, Niels, Groop, Leif, Grove, Megan L, Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B, Hayward, Caroline, Hirschhorn, Joel N, Holmen, Oddgeir L, Huffman, Jennifer, Huo, Yong, Hveem, Kristian, Jabeen, Sehrish, Jackson, Anne U, Jakobsdottir, Johanna, Jarvelin, Marjo-Riitta, Jensen, Gorm B, Jørgensen, Marit E, Jukema, J Wouter, Justesen, Johanne M, Kamstrup, Pia R, Kanoni, Stavroula, Karpe, Fredrik, Kee, Frank, Khera, Amit V, Klarin, Derek, Koistinen, Heikki A, Kooner, Jaspal S, Kooperberg, Charles, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo, Langenberg, Claudia, Langsted, Anne, Launer, Lenore J, Lauritzen, Torsten, Liewald, David C M, Lin, Li An, Linneberg, Allan, Loos, Ruth J F, Lu, Yingchang, Lu, Xiangfeng, Mägi, Reedik, Malarstig, Anders, Manichaikul, Ani, Manning, Alisa K, Mäntyselkä, Pekka, Marouli, Eirini, Masca, Nicholas G D, Maschio, Andrea, Meigs, James B, Melander, Olle, Metspalu, Andres, Morris, Andrew P, Morrison, Alanna C, Mulas, Antonella, Müller-Nurasyid, Martina, Munroe, Patricia B, Neville, Matt J, Nielsen, Jonas B, Nielsen, Sune F, Nordestgaard, Børge G, Ordovas, Jose M, Mehran, Roxana, O'Donnell, Christoper J, Orho-Melander, Marju, Molony, Cliona M, Muntendam, Pieter, Padmanabhan, Sandosh, Palmer, Colin N A, Pasko, Dorota, Patel, Aniruddh P, Pedersen, Oluf, Perola, Markus, Peters, Annette, Pisinger, Charlotta, Pistis, Giorgio, Polasek, Ozren, Poulter, Neil, Psaty, Bruce M, Rader, Daniel J, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Reiner, Alex P, Renström, Frida, Rich, Stephen S, Ridker, Paul M, Rioux, John D, Robertson, Neil R, Roden, Dan M, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J, Sanna, Serena, Sattar, Naveed, Schmidt, Ellen M, Scott, Robert A, Sever, Peter, Sevilla, Raquel S, Shaffer, Christian M, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S, Smith, Albert V, Smith, Blair H, Somayajula, Sangeetha, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Stirrups, Kathleen E, Stitziel, Nathan, Strauch, Konstantin, Stringham, Heather M, Surendran, Praveen, Tada, Hayato, Tall, Alan R, Tang, Hua, Tardif, Jean-Claude, Taylor, Kent D, Trompet, Stella, Tsao, Philip S, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, van Zuydam, Natalie R, Varbo, Anette, Varga, Tibor V, Virtamo, Jarmo, Waldenberger, Melanie, Wang, Nan, Wareham, Nick J, Warren, Helen R, Weeke, Peter E, Weinstock, Joshua, Wessel, Jennifer, Wilson, James G, Wilson, Peter W F, Xu, Ming, Yaghootkar, Hanieh, Young, Robin, Zeggini, Eleftheria, Zhang, He, Zheng, Neil S, Zhang, Weihua, Zhang, Yan, Zhou, Wei, Zhou, Yanhua, Zoledziewska, Magdalena, Howson, Joanna M M, Danesh, John, McCarthy, Mark I, Cowan, Chad A, Abecasis, Goncalo, Deloukas, Panos, Musunuru, Kiran, Willer, Cristen J, and Kathiresan, Sekar

Abstract

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

Published
2017
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273. How to properly assess dairy cow trace mineral status.

Author

WARREN, HELEN

Subjects
COW testing, DAIRY industry, ANIMAL feeds, INDUCTIVELY coupled plasma mass spectrometry, FARM supplies, POULTRY industry
Abstract

The article offers information about conducting a proper assessment on dairy cow trace mineral status, such as the use of inductively coupled plasma and mass spectroscopy. Other information such as sampling of tissues, which can be carried out ante or post-mortem, as well as blood sample accuracy is presented.

Published
2017

274. 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer:evidence from the Breast Cancer Association Consortium

Author

Warren, Helen, Dudbridge, Frank, Fletcher, Olivia, Orr, Nick, Johnson, Nichola, Hopper, John L, Apicella, Carmel, Southey, Melissa C, Mahmoodi, Maryam, Schmidt, Marjanka K, Broeks, Annegien, Cornelissen, Sten, Braaf, Linda M, Muir, Kenneth R, Lophatananon, Artitaya, Chaiwerawattana, Arkom, Wiangnon, Surapon, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Schulz-Wendtland, Ruediger, Sawyer, Elinor J, Tomlinson, Ian, Kerin, Michael, Burwinkel, Barbara, Marme, Frederik, Schneeweiss, Andreas, Sohn, Christof, Guénel, Pascal, Truong, Thérèse, Laurent-Puig, Pierre, Mulot, Claire, Bojesen, Stig E, Nielsen, Sune F, Flyger, Henrik, Nordestgaard, Børge G, Milne, Roger L, Benítez, Javier, Arias-Pérez, José-Ignacio, Zamora, M Pilar, Anton-Culver, Hoda, Ziogas, Argyrios, Bernstein, Leslie, Dur, Christina Clarke, Brenner, Hermann, Müller, Heiko, Arndt, Volker, Langheinz, Anne, Meindl, Alfons, Golatta, Michael, Warren, Helen, Dudbridge, Frank, Fletcher, Olivia, Orr, Nick, Johnson, Nichola, Hopper, John L, Apicella, Carmel, Southey, Melissa C, Mahmoodi, Maryam, Schmidt, Marjanka K, Broeks, Annegien, Cornelissen, Sten, Braaf, Linda M, Muir, Kenneth R, Lophatananon, Artitaya, Chaiwerawattana, Arkom, Wiangnon, Surapon, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Schulz-Wendtland, Ruediger, Sawyer, Elinor J, Tomlinson, Ian, Kerin, Michael, Burwinkel, Barbara, Marme, Frederik, Schneeweiss, Andreas, Sohn, Christof, Guénel, Pascal, Truong, Thérèse, Laurent-Puig, Pierre, Mulot, Claire, Bojesen, Stig E, Nielsen, Sune F, Flyger, Henrik, Nordestgaard, Børge G, Milne, Roger L, Benítez, Javier, Arias-Pérez, José-Ignacio, Zamora, M Pilar, Anton-Culver, Hoda, Ziogas, Argyrios, Bernstein, Leslie, Dur, Christina Clarke, Brenner, Hermann, Müller, Heiko, Arndt, Volker, Langheinz, Anne, Meindl, Alfons, and Golatta, Michael

Abstract

Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686).

Published
2012

275. Revisiting the role of trace minerals in dairy production.

Author

WARREN, HELEN

Subjects
TRACE elements, ANIMAL nutrition, PROTEIN synthesis, DNA, DEOXYRIBOSE
Abstract

The article offers information on trace minerals that play several roles in animal nutrition and have far-reaching consequences for body processes. Topics include examines that trace minerals are involved in protein synthesis, for example, Zn, which is required during the process involving the reading of DNA to make proteins.

Published
2021

279. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure underpinning obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas GD, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie CY, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Goncalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, de Bakker, Paul IW, de Groot, Mark CH, de Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, den Heijer, Martin, den Hollander, Anneke I, den Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, Easton, Douglas F, Edwards, Todd L, Ellinghaus, David, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D, Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franco, Oscar H, Franke, Andre, Franks, Paul W, Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P, Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan FA, Grarup, Niels, Griffiths, Helen L, Grove, Megan L, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Have, Christian T, Hayward, Caroline, He, Liang, Heard-Costa, Nancy L, Heath, Andrew C, Heid, Iris M, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W, Holmen, Oddgeir L, Hovingh, G Kees, Howson, Joanna MM, Hu, Yao, Huang, Paul L, Huffman, Jennifer E, Ikram, M Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Håkan, Jarvik, Gail P, Jensen, Gorm B, Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E, Jørgensen, Torben, Jukema, J Wouter, Kahali, Bratati, Kahn, René S, Kähönen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon LR, Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A, Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S, Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A, Lamparter, David, Lange, Ethan M, Lange, Leslie A, Langenberg, Claudia, Larson, Eric B, Lee, Nanette R, Lehtimäki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J, Liu, Yongmei, Lo, Ken Sin, Lophatananon, Artitaya, Lotery, Andrew J, Loukola, Anu, Luan, Jian'an, Lubitz, Steven A, Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L, McCarthy, Mark I, McKean-Cowdin, Roberta, Medland, Sarah E, Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L, Moilanen, Leena, Moitry, Marie, Montgomery, Grant W, Mook-Kanamori, Dennis O, Moore, Carmel, Mori, Trevor A, Morris, Andrew D, Morris, Andrew P, Müller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Narisu, Narisu, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njølstad, Pål R, Nordestgaard, Børge G, Nyholt, Dale R, O'Connel, Jeffrey R, O’Donoghue, Michelle L., Olde Loohuis, Loes M, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin NA, Palmer, Nicholette D, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John RB, Pers, Tune H, Person, Thomas N, Peters, Annette, Petersen, Eva RB, Peyser, Patricia A, Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J, Puolijoki, Hannu, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Renström, Frida, Rheinberger, Myriam, Ridker, Paul M, Rioux, John D, Rivas, Manuel A, Roberts, David J, Robertson, Neil R, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati H, Sheu, Wayne H-H, Sim, Xueling, Slater, Andrew J, Small, Kerrin S, Smith, Albert Vernon, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E, Strauch, Konstantin, Stringham, Heather M, Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J, Tada, Hayato, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H, Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, André G, Uusitupa, Matti, van der Laan, Sander W, van Duijn, Cornelia M, van Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Velez Edwards, Digna R, Vermeulen, Sita H, Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E, Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Ware, Erin B, Wareham, Nicholas J, Warren, Helen R, Waterworth, Dawn M, Wessel, Jennifer, White, Harvey D, Willer, Cristen J, Wilson, James G, Witte, Daniel R, Wood, Andrew R, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I, Pospisilik, John A, Rivadeneira, Fernando, Borecki, Ingrid B, Deloukas, Panos, Frayling, Timothy M, Lettre, Guillaume, North, Kari E, Lindgren, Cecilia M, Hirschhorn, Joel N, and Loos, Ruth JF

Abstract

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, non-coding variants from which pinpointing causal genes remains challenging. Here, we combined data from 718,734 individuals to discover rare and low-frequency (MAF<5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which eight in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2, ZNF169) newly implicated in human obesity, two (MC4R, KSR2) previously observed in extreme obesity, and two variants in GIPR. Effect sizes of rare variants are ~10 times larger than of common variants, with the largest effect observed in carriers of an MC4R stop-codon (p.Tyr35Ter, MAF=0.01%), weighing ~7kg more than non-carriers. Pathway analyses confirmed enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically-supported therapeutic targets to treat obesity.

Published
2018
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280. Forage analysis crucial to accurate ruminant rations.

Author

WARREN, HELEN

Subjects
FORAGE plant quality, FORAGE plant harvesting, DRY matter content of plants, COMPOSITION of forage plants, FORAGE plant yield
Abstract

The article discusses the factors of forage analysis in rationing ruminant livestock, detailing its parameters of energy and protein, assessment of hygiene quality and dry matter (DM). An overview on the concept of forage analysis and the use of near-infrared reflectance spectroscopy (NIRS) is explored. It also highlights the principles of rationing in ensuring the demand and supply of forage products.

Published
2017

281. How nutrition influences dairy cow health, immunity.

Author

WARREN, HELEN

Subjects
COWS, IMMUNE system, ANIMAL nutrition, IMMUNE response, PATHOGENIC microorganisms
Abstract

The article offers information for animal producers and farmers about how balanced nutrition influences the immune function and performance in transition cows. It provides an overview of the immune system, a biological defense system composed of different structures, cell types, and processes that act to protect the host animal from pathogens, including microorganisms, viruses, and parasites, as well as factors affecting immune function.

Published
2017

282. A genome-wide interaction analysis of tricyclic/tetracyclic antidepressants and RR and QT intervals: a pharmacogenomics study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium

Author

Noordam, Raymond, Sitlani, Colleen M, Avery, Christy L, Stewart, James D, Gogarten, Stephanie M, Wiggins, Kerri L, Trompet, Stella, Warren, Helen R, Sun, Fangui, Evans, Daniel S, Li, Xiaohui, Li, Jin, Smith, Albert V, Bis, Joshua C, Brody, Jennifer A, Busch, Evan L, Caulfield, Mark J, Chen, Yii-Der I, Cummings, Steven R, Cupples, L Adrienne, Duan, Qing, Franco, Oscar H, Máéndez-Giráéáldez, Rául, Harris, Tamara B, Heckbert, Susan R, van Heemst, Diana, Hofman, Albert, Floyd, James S, Kors, Jan A, Launer, Lenore J, Li, Yun, Li-Gao, Ruifang, Lange, Leslie A, Lin, Henry J, de Mutsert, Renáéáée, Napier, Melanie D, Newton-Cheh, Christopher, Poulter, Neil, Reiner, Alexander P, Rice, Kenneth M, Roach, Jeffrey, Rodriguez, Carlos J, Rosendaal, Frits R, Sattar, Naveed, Sever, Peter, Seyerle, Amanda A, Slagboom, P Eline, Soliman, Elsayed Z, Sotoodehnia, Nona, Stott, David J, Sturmer, Til, Taylor, Kent D, Thornton, Timothy A, Uitterlinden, Andráéáéé G, Wilhelmsen, Kirk C, Wilson, James G, Gudnason, Vilmundur, Jukema, J Wouter, Laurie, Cathy C, Liu, Yongmei, Mook-Kanamori, Dennis O, Munroe, Patricia B, Rotter, Jerome I, Vasan, Ramachandran S, Psaty, Bruce M, Stricker, Bruno H, and Whitsel, Eric A

Abstract

BackgroundIncreased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/tetracyclic antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals.Methods and resultsWe conducted race/ethnic-specific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45 706; n=1417 TCA users), African (n=10 235; n=296 TCA users) and Hispanic/Latino (n=13 808; n=147 TCA users) ancestry, adjusted for clinical covariates. Among the populations of European ancestry, two genome-wide significant loci were identified for RR interval: rs6737205 in BRE(β=56.3, pinteraction=3.9e−9) and rs9830388 in UBE2E2(β=25.2, pinteraction=1.7e−8). In Hispanic/Latino cohorts, rs2291477 in TGFBR3significantly modified the association between TCAs and QT intervals (β=9.3, pinteraction=2.55e−8). In the meta-analyses of the other ethnicities, these loci either were excluded from the meta-analyses (as part of quality control), or their effects did not reach the level of nominal statistical significance (pinteraction>0.05). No new variants were identified in these ethnicities. No additional loci were identified after inverse-variance-weighted meta-analysis of the three ancestries.ConclusionsAmong Europeans, TCA interactions with variants in BREand UBE2E2were identified in relation to RR intervals. Among Hispanic/Latinos, variants in TGFBR3modified the relation between TCAs and QT intervals. Future studies are required to confirm our results.

Published
2017
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289. Yeast in ruminant diets yields many benefits: The right strains of yeast will provide a natural gut flora stabilizer in cows.

Author

WARREN, HELEN

Subjects
YEAST as feed, RUMINANTS, FERMENTATION, FATTY acids
Abstract

The article highlights the consideration of several yeast strains into ruminant animal diets. Topics include the presence of microbial fermentation in the reticulorumen of dairy cows that breakdowns dietary ingredients into Volatile fatty acids (VFA); and the reduction of acidosis in cattle by decreasing lactate.

Published
2020

290. Examining the components of optimal dairy cow nutrition: A review of the fundamental nutrition criteria for efficient dairy production.

Author

WARREN, HELEN

Subjects
NUTRITIONAL requirements, CATTLE feeding & feeds, COMPOSITION of dairy products, ORGANIC compounds, BIOAVAILABILITY
Abstract

The article present reports on nutrition components for dairy production. Topics include proper balance between energy and proteins in dairy rations impact the nutrient supply and accumulation; various biological processes are influenced by the minerals and vitamins; and enhance bioavailability due to organic forms of trace minerals with immunity and production benefits.

Published
2019

291. The Janus influence and discovering a life : a study of people living with coexisting mental health and substance use disorders : a thesis presented in fulfilment of the requirements for the degree of Doctor of Philosophy in Sociology at Massey University, Albany, New Zealand

Author

Warren, Helen Barbara and Warren, Helen Barbara

Abstract

This grounded study examines how people who are dually diagnosed with a major mental illness and substance use disorder 'recover' their lives from a past of 'intemperate insanity' and discover a world in a rich and productive present. Thirty participants, including consumers, staff and families, took part in the study. Additional slices of data were retrieved from the analysis of six 'policy' documents and 72 hours of participant observation. All data were constantly compared and analysed using Glaser's emergent approach to grounded theory. Research and literature on those with coexisting disorders has been dominated by the 'medical model' with a focus on assessment, diagnosis, treatment and rehabilitation both in addiction and mental health settings. Whilst these aspects of 'management' of coexisting disorders are important, this acute phase of intervention represents only a small fragment of a person's life. These people are not their disease, and the coexisting disorders are not the totality of their being. 'Discovering a life' was an emergent theme that formed the basic core category. Intemperate insanity, naked in Woolworths (the crisis), shedding the armour (recovery) and living without the armour (maintaining the change) and Janus' temple (service provision) formed the theoretical codes which made up the entity discovering a life. There also emerged a further 'natural division', a critical juncture essential to discovering a life - sobriety. Without sobriety, participants' lives took a different path which linked them back to a past of intemperate insanity. Literary images of the Roman God Janus are used as a metaphor throughout the thesis to elucidate aspects of the participants' lives. Janus was the God of endings and new beginnings, of youth and age, and is portrayed in historical texts with a double head, one looking backwards and the other forwards. It is this need to remind themselves of the past in order to imagine the future, a need to track the metap

Published
2001

292. Genome-Wide Association Study of Blood Pressure Traits by Hispanic/Latino Background: the Hispanic Community Health Study/Study of Latinos

Author

Sofer, Tamar, Wong, Quenna, Hartwig, Fernando P., Taylor, Kent, Warren, Helen R., Evangelou, Evangelos, Cabrera, Claudia P., Levy, Daniel, Kramer, Holly, Lange, Leslie A., Horta, Bernardo L., Liang, Jingjing, Le, Thu H., Edwards, Digna R. Velez, Tayo, Bamidele O., Gaulton, Kyle J., Smith, Jennifer A., Lu, Yingchang, Jensen, Richard A., Chen, Guanjie, Yanek, Lisa R., Schwander, Karen, Tajuddin, Salman M., Kim, Wonji, Kayima, James, McKenzie, Colin A., Fox, Ervin, Nalls, Michael A., Young, Hunter J., Sun, Yan, Lane, Jacqueline M., Cechova, Sylvia, Zhou, Jie, Tang, Hua, Fornage, Myriam, Musani, Solomon K., Wang, Heming, Lee, Juyoung, Adeyemo, Adebowale, Dreisbach, Albert W., Forrester, Terrence, Chu, Pei-Lun, Cappola, Anne, Evans, Michele K., Morrison, Alanna C., Martin, Lisa W., Wiggins, Kerri L., Hui, Qin, Zhao, Wei, Jackson, Rebecca D., Ware, Erin B., Faul, Jessica D., Bray, Michael, Danny, Joshua C., Mosley, Thomas H., Palmas, Walter, Guo, Xiuqing, Papanicolaou, George J., Penman, Alan D., Polak, Joseph F., Rice, Kenneth, Boerwinkle, Eric, Bottinger, Erwin P., Liu, Kiang, Risch, Neil, Hunt, Steven C., Kooperberg, Charles, Zonderman, Alan B., Laurie, Cathy C., Becker, Diane M., Cai, Jianwen, Loos, Ruth J. F., Psaty, Bruce M., Weir, David R., Kardia, Sharon L. R., Arnett, Donna K, Won, Sungho, Edwards, Todd L., Redline, Susan, Cooper, Richard S., Rao, D. C., Rotimi, Charles, Chadravarti, Aravinda, Zhu, Xiaofeng, Kerr, Kathleen F., Reiner, Alex P., and Franceschini, Nora

Abstract

Hypertension prevalence varies between ethnic groups, possibly due to differences in genetic, environmental, and cultural determinants. Hispanic/Latino Americans are a diverse and understudied population. We performed a genome-wide association study (GWAS) of blood pressure (BP) traits in 12,278 participants from the Hispanics Community Health Study/Study of Latinos (HCHS/SOL). In the discovery phase we identified eight previously unreported BP loci. In the replication stage, we tested these loci in the 1982 Pelotas Birth Cohort Study of admixed Southern Brazilians, the COGENT-BP study of African descent, women of European descent from the Women Health Initiative (WHI), and a sample of European descent from the UK Biobank. No loci met the Bonferroni-adjusted level of statistical significance (0.0024). Two loci had marginal evidence of replication: rs78701042 (NGF) with diastolic BP (P = 0.008 in the 1982 Pelotas Birth Cohort Study), and rs7315692 (SLC5A8) with systolic BP (P = 0.007 in European ancestry replication). We investigated whether previously reported loci associated with BP in studies of European, African, and Asian ancestry generalize to Hispanics/Latinos. Overall, 26% of the known associations in studies of individuals of European and Chinese ancestries generalized, while only a single association previously discovered in a people of African descent generalized.

Published
2017
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293. 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 S. F., 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., Lehtimäki, Terho, Gudnason, Vilmundur, Wilson, James, Lubitz, Steven A., Kääb, Stefan, Sotoodehnia, Nona, Caulfield, Mark J., Palmer, Colin N. A., Sanna, Serena, Mook-Kanamori, Dennis O., Deloukas, Panos, Pedersen, Oluf, Rotter, Jerome I., Dörr, Marcus, O'Donnell, Chris J., Hayward, Caroline, Arking, Dan E., Kooperberg, Charles, van der Harst, Pim, Eijgelsheim, Mark, Stricker, Bruno H., and Munroe, Patricia B.

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
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294. 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.

Abstract

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N= 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Published
2022
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297. Tips for maximizing forage in ruminant rations: Fiber is a critical component of ruminant diets and offers numerous health and productivity benefits.

Author

WARREN, HELEN

Subjects
FIBER in animal nutrition, FORAGE, RUMINANTS, FATTY acids, FIBER content of feeds
Abstract

The article shares tips to help livestock farmers maximize energy from forage in ruminant rations by increasing forage fiber utilization and digestion. Topics discussed include the benefits of fiber within forage, the role of volatile fatty acids (VFAs) as the primary energy source for ruminants, and potential mechanisms that can impair the degradation of fiber.

Published
2019

298. Nutritional factors that influence milk quality, composition: The relationship between milk components provides a glimpse into cow health.

Author

WARREN, HELEN

Subjects
HEALTH of cattle, COMPOSITION of milk, COWS, ANIMAL nutrition, MILK, CATTLE breeding
Abstract

The article focuses on relationship between cow health especially nutrition, and milk components and quality. Topics include non-nutritional factors that affect milk components and quality such as health status, season and body condition, influence of milk component levels by diet composition, and regulation of milk urea nitrogen levels which is affected by feeding system, time after feeding, breed, season and diet balance.

Published
2019

299. The role of gut microbiota in animal health, well-being.

Author

WARREN, HELEN

Subjects
GUT microbiome, ANIMAL health, MICROBIAL diversity, POULTRY feeding, LIVESTOCK, ANIMAL nutrition
Abstract

The author discusses the role of gut microbiota in the health and well-being of animals, and mentions ways to enhance diversity in the intestinal microbiota of livestock and poultry through dietary interventions. Topics include the involvement of the microbial community within the guts in immune function, pathogen control, and intestinal morphology, colonization resistance, and antimicrobial resistance (AMR).

Published
2019

300. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas GD, Ng, Maggie CY, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bonnycastle, Lori L, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Carey, David J, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul IW, de Borst, Gert J., de Denus, Simon, de Groot, Mark CH, de Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, den Hollander, Anneke I, Dennis, Joe G, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M, Easton, Douglas F, Ebeling, Tapani, Edwards, Todd L, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D, Feitosa, Mary F, Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franks, Paul W, Frikke-Schmidt, Ruth, Galesloot, Tessel E, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D, Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, He, Liang, Heid, Iris M, Heikkilä, Kauko, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Hovingh, G. Kees, Howson, Joanna MM, Hoyng, Carel B, Huang, Paul L, Hveem, Kristian, Ikram, M. 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Abstract

Summary Height is a highly heritable, classic polygenic trait with ∼700 common associated variants identified so far through genome-wide association studies. Here, we report 83 height-associated coding variants with lower minor allele frequencies (range of 0.1-4.8%) and effects of up to 2 cm/allele (e.g. in IHH, STC2, AR and CRISPLD2), >10 times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (+1-2 cm/allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates (e.g. ADAMTS3, IL11RA, NOX4) and pathways (e.g. proteoglycan/glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate to large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Published
2016
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