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558 results on '"McKenzie, Colin A."'

53. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author

Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O’Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sõber, Siim, Parsa, Afshin, Luan, Jian’an, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F, Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Nguyen, Khanh-Dung Hoang, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Onland-Moret, Charlotte N., Cooper, Matthew N., Platou, Carl G. P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S. P. M., Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., O’Connell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Kardia, Sharon L., Morrison, Alanna C., Hernandez, Dena, Najjar, Samer, McArdle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N.M., Lawlor, Debbie A., Beilby, John P., Lawrence, Robert W., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Dreisbach, Albert W., Li, Yali, Young, Hunter J., Bis, Joshua C., Kähönen, Mika, Viikari, Jorma, Adair, Linda S., Lee, Nanette R., Chen, Ming-Huei, Olden, Matthias, Pattaro, Cristian, Bolton, Judith A. Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M., Islam, Muhammad, Jafar, Tazeen H., Erdmann, Jeanette, Kulkarni, Smita R., Bornstein, Stefan R., Grässler, Jürgen, Groop, Leif, Voight, Benjamin F., Kettunen, Johannes, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inês, Khaw, Kay-Tee, Weder, Alan B., Hunt, Steven C., Sun, Yan V., Bergman, Richard N., Collins, Francis S., Bonnycastle, Lori L., Scott, Laura J., Stringham, Heather M., Peltonen, Leena, Perola, Markus, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A., Wang, Thomas J., Burton, Paul R., Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K., Rudock, Megan E., Heckbert, Susan R., Smith, Nicholas L., Wiggins, Kerri L., Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margus, Kinra, Sanjay, Prabhakaran, Dorairaj, Tripathy, Vikal, Langefeld, Carl D., Rosengren, Annika, Thelle, Dag S., Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, McKenzie, Colin A., Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thomas, Wichmann, Erich H., Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, James, Sehmi, Joban S., Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J., Yao, Jie, Kathiresan, Sekar, O’Donnell, Christopher J., Schwartz, Stephen M., Ikram, Arfan M., Longstreth, W. T., Jr, Mosley, Thomas H., Seshadri, Sudha, Shrine, Nick R.G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Anders, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Mani, Radha K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U. S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Ong, Rick Twee-Hee, Dörr, Marcus, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Panos, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Janos, Kumar, Kranthi M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, Gerald F.R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charles, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Maris, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Tai, Shyong E, Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M, Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. G., Altshuler, David, Loos, Ruth J. F., Shuldiner, Alan R., Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G., Wareham, Nicholas J., Gudnason, Vilmundur, Rotter, Jerome I., Rettig, Rainer, Uda, Manuela, Strachan, David P., Witteman, Jacqueline C. M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Vasan, Ramachandran S., Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., and Johnson, Toby

Published
2011
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54. Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

Author

Fox, Ervin R., Young, J. Hunter, Li, Yali, Dreisbach, Albert W., Keating, Brendan J., Musani, Solomon K., Liu, Kiang, Morrison, Alanna C., Ganesh, Santhi, Kutlar, Abdullah, Ramachandran, Vasan S., Polak, Josef F., Fabsitz, Richard R., Dries, Daniel L., Farlow, Deborah N., Redline, Susan, Adeyemo, Adebowale, Hirschorn, Joel N., Sun, Yan V., Wyatt, Sharon B., Penman, Alan D., Palmas, Walter, Rotter, Jerome I., Townsend, Raymond R., Doumatey, Ayo P., Tayo, Bamidele O., Mosley, Thomas H., Jr, Lyon, Helen N., Kang, Sun J., Rotimi, Charles N., Cooper, Richard S., Franceschini, Nora, Curb, J. David, Martin, Lisa W., Eaton, Charles B., Kardia, Sharon L.R., Taylor, Herman A., Caulfield, Mark J., Ehret, Georg B., Johnson, Toby, Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, OʼReilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sõber, Siim, Parsa, Afshin, Luan, Jianʼan, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Kumari, Meena, JinGo, Min, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D.G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Seielstad, Mark, Sim, Xueling, Nguyen, Khanh-Dung Hoang, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., Cooper, Matthew N., Platou, Carl G.P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S.P.M., Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., OʼConnell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Hernandez, Dena, Najjar, Samer, McArdle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N.M., Lawlor, Debbie A., Beilby, John P., Lawrence, Robert W., Clarke, Robert, Collins, Rory, Hopewell, Jemma C., Ongen, Halit, Bis, Joshua C., Kähönen, Mika, Viikari, Jorma, Adair, Linda S., Lee, Nanette R., Chen, Ming-Huei, Olden, Matthias, Pattaro, Cristian, Hoffman Bolton, Judith A., Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M., Islam, Muhammad, Jafar, Tazeen H., Erdmann, Jeanette, Kulkarni, Smita R., Bornstein, Stefan R., Grässler, Jürgen, Groop, Leif, Voight, Benjamin F., Kettunen, Johannes, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inês, Khaw, Kay-Tee, Weder, Alan B., Hunt, Steven C., Bergman, Richard N., Collins, Francis S., Bonnycastle, Lori L., Scott, Laura J., Stringham, Heather M., Peltonen, Leena, Perola, Markus, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A., Wang, Thomas J., Burton, Paul R., SolerArtigas, Maria, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K., Rudock, Megan E., Heckbert, Susan R., Smith, Nicholas L., Wiggins, Kerri L., Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margus, Kinra, Sanjay, Prabhakaran, Dorairajan, Tripathy, Vikal, Langefeld, Carl D., Rosengren, Annika, Thelle, Dag S., MariaCorsi, Anna, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, McKenzie, Colin A., Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thomas, Wichmann, H.-Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, James, Sehmi, Joban S., Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J., Yao, Jie, Kathiresan, Sekar, OʼDonnell, Chris, Schwartz, Steven M., Arfan Ikram, M., Longstreth, Will T., Jr, Seshadri, Sudha, Shrine, Nick R.G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Anders, Watkins, Hugh, Bakker, Stephan J.L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U.S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würz, Peter, Twee-Hee Ong, Rick, Dörr, Marcus, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Panos, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Janos, Kranthi Kumar, M.J., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, Gerald R., Charchar, Fadi J., Schwarz, Peter E.H., Hayward, Caroline, Guo, Xiuqing, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Maris, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Wong, Tien Y., Shyong Tai, E., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J.G., Altshuler, David, Loos, Ruth J.F., Shuldiner, Alan R., Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G., Wareham, Nicholas J., Gudnason, Vilmundur, Rettig, Rainer, Uda, Manuela, Strachan, David P., Witteman, Jacqueline C.M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Chakravarti, Aravinda, Zhu, Xiaofeng, and Levy, Daniel

Published
2011
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56. Remembering Laura Corrigan

Author

Baker, Karis, primary, Bracken, Fiona, additional, Corrigan, Rich, additional, Creer, Simon, additional, Foote, Andy, additional, Fotherby, Heather, additional, Gray, Howard, additional, Lucas, Martyn, additional, Mariani, Stefano, additional, McKenzie, Colin, additional, and McKew, Boyd, additional

Published
2020
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59. Fine mapping of the association with obesity at the FTO locus in African-derived populations

Author

Hassanein, Mohamed T., Lyon, Helen N., Nguyen, Thutrang T., Akylbekova, Ermeg L., Waters, Kevin, Lettre, Guillaume, Tayo, Bamidele, Forrester, Terrence, Sarpong, Daniel F., Stram, Dan O., Butler, Johannah L., Wilks, Rainford, Liu, Jiankang, Le Marchand, Loic, Kolonel, Laurence N., Zhu, Xiaofeng, Henderson, Brian, Cooper, Richard, McKenzie, Colin, Taylor, Herman A., Jr, Haiman, Christopher A., and Hirschhorn, Joel N.

Published
2010
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60. Genome-wide association of anthropometric traits in African- and African-derived populations

Author

Kang, Sun J., Chiang, Charleston W.K., Palmer, Cameron D., Tayo, Bamidele O., Lettre, Guillaume, Butler, Johannah L., Hackett, Rachel, Adeyemo, Adebowale A., Guiducci, Candace, Berzins, Ilze, Nguyen, Thutrang T., Feng, Tao, Luke, Amy, Shriner, Daniel, Ardlie, Kristin, Rotimi, Charles, Wilks, Rainford, Forrester, Terrence, McKenzie, Colin A., Lyon, Helen N., Cooper, Richard S., Zhu, Xiaofeng, and Hirschhorn, Joel N.

Published
2010
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68. Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Author

Bentley, Amy R, Sung, Yun J, Brown, Michael R, Winkler, Thomas W, Kraja, Aldi T, Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M, Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Hung, Yi-Jen, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Prins, Bram, Riaz, Muhammad, Robino, Antonietta, Said, M Abdullah, Schupf, Nicole, Scott, Robert A, Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Tzung-Dau, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Xiang, Yong-Bing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Adeyemo, Adebowale, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Arzumanyan, Zorayr, Aung, Tin, Ballantyne, Christie, Barr, R Graham, Bielak, Lawrence F, Boerwinkle, Eric, Bottinger, Erwin P, Broeckel, Ulrich, Brown, Morris, Cade, Brian E, Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Christensen, Kaare, Concas, Maria Pina, Connell, John M, de las Fuentes, Lisa, de Silva, H Janaka, de Vries, Paul S, Doumatey, Ayo, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Floyd, James S, Forouhi, Nita G, Forrester, Terrence, Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gharib, Sina A, Gigante, Bruna, Giulianini, Franco, Grabe, Hans J, Gu, C Charles, Harris, Tamara B, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E, Ikram, M Arfan, Jia, Yucheng, Joehanes, Roby, Johnson, Craig, Jonas, Jost Bruno, Justice, Anne E, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E, Kritchevsky, Stephen B, Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lehne, Benjamin, Lewis, Cora E, Li, Yize, Liang, Jingjing, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Kiang, Loh, Marie, Lohman, Kurt K, Louie, Tin, Luzzi, Anna, Magi, Reedik, Mahajan, Anubha, Manichaikul, Ani W, McKenzie, Colin A, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L, Momozawa, Yukihide, Morris, Andrew P, Murray, Alison D, Nalls, Mike A, Nauck, Matthias, Nelson, Christopher P, North, Kari E, O'Connell, Jeffrey R, Palmer, Nicholette D, Papanicolau, George J, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Polasek, Ozren, Poulter, Neil, Raitakari, Olli T, Reiner, Alex P, Renstrom, Frida, Rice, Treva K, Rich, Stephen S, Robinson, Jennifer G, Rose, Lynda M, Rosendaal, Frits R, Rudan, Igor, Schmidt, Carsten O, Schreiner, Pamela J, Scott, William R, Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Jennifer A, Snieder, Harold, Starr, John M, Strauch, Konstantin, Stringham, Heather M, Tan, Nicholas YQ, Tang, Hua, Taylor, Kent D, Teo, Yik Ying, Tham, Yih Chung, Tiemeier, Henning, Turner, Stephen T, Uitterlinden, Andre G, van Heemst, Diana, Waldenberger, Melanie, Wang, Heming, Wang, Lan, Wang, Lihua, Wei, Wen Bin, Williams, Christine A, Sr, Wilson Gregory, Wojczynski, Mary K, Yao, Jie, Young, Kristin, Yu, Caizheng, Yuan, Jian-Min, Zhou, Jie, Zonderman, Alan B, Becker, Diane M, Boehnke, Michael, Bowden, Donald W, Chambers, John C, Cooper, Richard S, de Faire, Ulf, Deary, Ian J, Elliott, Paul, Esko, Tonu, Farrall, Martin, Franks, Paul W, Freedman, Barry I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L, Juang, Jyh-Ming Jimmy, Kamatani, Yoichiro, Kammerer, Candace M, Kato, Norihiro, Kooner, Jaspal S, Laakso, Markku, Laurie, Cathy C, Lee, I-Te, Lehtimaki, Terho, Magnusson, Patrik KE, Oldehinkel, Albertine J, Penninx, Brenda WJH, Pereira, Alexandre C, Rauramaa, Rainer, Redline, Susan, Samani, Nilesh J, Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E, Wang, Jun-Sing, Wang, Ya Xing, Wareham, Nicholas J, Watkins, Hugh, Weir, David R, Wickremasinghe, Ananda R, Wu, Tangchun, Zeggini, Eleftheria, Zheng, Wei, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Kardia, Sharon LR, Liu, Yongmei, Psaty, Bruce M, Ridker, Paul M, van Dam, Rob M, Mook-Kanamori, Dennis O, Fornage, Myriam, Province, Michael A, Kelly, Tanika N, Fox, Ervin R, Hayward, Caroline, van Duijn, Cornelia M, Tai, E Shyong, Wong, Tien Yin, Loos, Ruth JF, Franceschini, Nora, Rotter, Jerome I, Zhu, Xiaofeng, Bierut, Laura J, Gauderman, W James, Rice, Kenneth, Munroe, Patricia B, Morrison, Alanna C, Rao, Dabeeru C, Rotimi, Charles N, Cupples, L Adrienne, Consortium, COGENT-Kidney, Consortium, EPIC-InterAct, Grp, Understanding Soc Sci, Cohort, Lifelines, National Institutes of Health [Bethesda] (NIH), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), The University of Texas Health Science Center at Houston (UTHealth), Universität Regensburg (UR), Queen Mary University of London (QMUL), Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), School of Public Health [Boston], Boston University [Boston] (BU), Los Angeles Biomedical Research Institute (LA BioMed), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Singapore Eye Research Institute [Singapore] (SERI), Duke-NUS Medical School [Singapore], National University of Singapore (NUS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Edinburgh, University of Mississippi Medical Center (UMMC), University of Georgia [USA], Leiden University Medical Center (LUMC), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Harvard T.H. Chan School of Public Health, University of Washington [Seattle], Wake Forest University, Genome Institute of Singapore (GIS), Massachusetts General Hospital [Boston], Pennington Biomedical Research Center, Louisiana State University (LSU), Icelandic Heart Association [Kopavogur, Iceland] (IHA), University of Iceland [Reykjavik], University of Michigan [Ann Arbor], University of Michigan System, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Tartu, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Imperial College London, University of Ioannina, University of Oxford [Oxford], University of Groningen [Groningen], Universidade Federal de Pelotas = Federal University of Pelotas (UFPel), University of Bristol [Bristol], Huazhong University of Science and Technology [Wuhan] (HUST), Universidade de São Paulo Medical School (FMUSP), Case Western Reserve University [Cleveland], University of Southern California (USC), This project was largely supported by a grant from the US National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL118305) and by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health through the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362)., Bentley, Ar, Sung, Yj, Brown, Mr, Winkler, Tw, Kraja, At, Ntalla, I, Schwander, K, Chasman, Di, Lim, E, Deng, X, Guo, X, Liu, J, Lu, Y, Cheng, Cy, Sim, X, Vojinovic, D, Huffman, Je, Musani, Sk, Li, C, Feitosa, Mf, Richard, Ma, Noordam, R, Baker, J, Chen, G, Aschard, H, Bartz, Tm, Ding, J, Dorajoo, R, Manning, Ak, Rankinen, T, Smith, Av, Tajuddin, Sm, Zhao, W, Graff, M, Alver, M, Boissel, M, Chai, Jf, Chen, X, Divers, J, Evangelou, E, Gao, C, Goel, A, Hagemeijer, Y, Harris, Se, Hartwig, Fp, He, M, Horimoto, Arvr, Hsu, Fc, Hung, Yj, Jackson, Au, Kasturiratne, A, Komulainen, P, Kühnel, B, Leander, K, Lin, Kh, Luan, J, Lyytikäinen, Lp, Matoba, N, Nolte, Im, Pietzner, M, Prins, B, Riaz, M, Robino, A, Said, Ma, Schupf, N, Scott, Ra, Sofer, T, Stancáková, A, Takeuchi, F, Tayo, Bo, van der Most, Pj, Varga, Tv, Wang, Td, Wang, Y, Ware, Eb, Wen, W, Xiang, Yb, Yanek, Lr, Zhang, W, Zhao, Jh, Adeyemo, A, Afaq, S, Amin, N, Amini, M, Arking, De, Arzumanyan, Z, Aung, T, Ballantyne, C, Barr, Rg, Bielak, Lf, Boerwinkle, E, Bottinger, Ep, Broeckel, U, Brown, M, Cade, Be, Campbell, A, Canouil, M, Charumathi, S, Chen, Yi, Christensen, K, COGENT-Kidney, Consortium, Concas, Mp, Connell, Jm, de Las Fuentes, L, de Silva, Hj, de Vries, P, Doumatey, A, Duan, Q, Eaton, Cb, Eppinga, Rn, Faul, Jd, Floyd, J, Forouhi, Ng, Forrester, T, Friedlander, Y, Gandin, I, Gao, H, Ghanbari, M, Gharib, Sa, Gigante, B, Giulianini, F, Grabe, Hj, Gu, Cc, Harris, Tb, Heikkinen, S, Heng, Ck, Hirata, M, Hixson, Je, Ikram, Ma, EPIC-InterAct, Consortium, Jia, Y, Joehanes, R, Johnson, C, Jonas, Jb, Justice, Ae, Katsuya, T, Khor, Cc, Kilpeläinen, To, Koh, Wp, Kolcic, I, Kooperberg, C, Krieger, Je, Kritchevsky, Sb, Kubo, M, Kuusisto, J, Lakka, Ta, Langefeld, Cd, Langenberg, C, Launer, Lj, Lehne, B, Lewis, Ce, Li, Y, Liang, J, Lin, S, Liu, Ct, Liu, K, Loh, M, Lohman, Kk, Louie, T, Luzzi, A, Mägi, R, Mahajan, A, Manichaikul, Aw, Mckenzie, Ca, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, Kl, Momozawa, Y, Morris, Ap, Murray, Ad, Nalls, Ma, Nauck, M, Nelson, Cp, North, Ke, O'Connell, Jr, Palmer, Nd, Papanicolau, Gj, Pedersen, Nl, Peters, A, Peyser, Pa, Polasek, O, Poulter, N, Raitakari, Ot, Reiner, Ap, Renström, F, Rice, Tk, Rich, S, Robinson, Jg, Rose, Lm, Rosendaal, Fr, Rudan, I, Schmidt, Co, Schreiner, Pj, Scott, Wr, Sever, P, Shi, Y, Sidney, S, Sims, M, Smith, Ja, Snieder, H, Starr, Jm, Strauch, K, Stringham, Hm, Tan, Nyq, Tang, H, Taylor, Kd, Teo, Yy, Tham, Yc, Tiemeier, H, Turner, St, Uitterlinden, Ag, Understanding Society Scientific, Group, van Heemst, D, Waldenberger, M, Wang, H, Wang, L, Wei, Wb, Williams, Ca, Wilson, G Sr, Wojczynski, Mk, Yao, J, Young, K, Yu, C, Yuan, Jm, Zhou, J, Zonderman, Ab, Becker, Dm, Boehnke, M, Bowden, Dw, Chambers, Jc, Cooper, R, de Faire, U, Deary, Ij, Elliott, P, Esko, T, Farrall, M, Franks, Pw, Freedman, Bi, Froguel, P, Gasparini, P, Gieger, C, Horta, Bl, Juang, Jj, Kamatani, Y, Kammerer, Cm, Kato, N, Kooner, J, Laakso, M, Laurie, Cc, Lee, It, Lehtimäki, T, Lifelines, Cohort, Magnusson, Pke, Oldehinkel, Aj, Penninx, Bwjh, Pereira, Ac, Rauramaa, R, Redline, S, Samani, Nj, Scott, J, Shu, Xo, van der Harst, P, Wagenknecht, Le, Wang, J, Wang, Yx, Wareham, Nj, Watkins, H, Weir, Dr, Wickremasinghe, Ar, Wu, T, Zeggini, E, Zheng, W, Bouchard, C, Evans, Mk, Gudnason, V, Kardia, Slr, Liu, Y, Psaty, Bm, Ridker, Pm, van Dam, Rm, Mook-Kanamori, Do, Fornage, M, Province, Ma, Kelly, Tn, Fox, Er, Hayward, C, van Duijn, Cm, Tai, E, Wong, Ty, Loos, Rjf, Franceschini, N, Rotter, Ji, Zhu, X, Bierut, Lj, Gauderman, Wj, Rice, K, Munroe, Pb, Morrison, Ac, Rao, Dc, Rotimi, Cn, Cupples, La., Luan, Jian'an [0000-0003-3137-6337], Pietzner, Maik [0000-0003-3437-9963], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Home Office, Action on Hearing Loss, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), Universiteit Leiden, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), University of Oxford, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, and APH - Digital Health

Subjects
Male, Linkage disequilibrium, Blood lipids, Genome-wide association study, VARIANTS, SUSCEPTIBILITY, Environment interaction, Genome, Linkage Disequilibrium, MESH: Genotype, 0302 clinical medicine, MESH: Aged, 80 and over, Genotype, NICOTINE METABOLISM, 11 Medical and Health Sciences, Genetics & Heredity, Aged, 80 and over, Genetics, MESH: Aged, 0303 health sciences, ARCHITECTURE, [STAT.AP]Statistics [stat]/Applications [stat.AP], Genotype imputation, MESH: Middle Aged, CHOLESTEROL, Smoking, MESH: Life Style, Lifelines Cohort, Middle Aged, Lipids, 3. Good health, ENVIRONMENT INTERACTION, GENOTYPE IMPUTATION, RISK LOCI, METAANALYSIS, CIGARETTES, Cholesterol, MESH: Linkage Disequilibrium, MESH: Young Adult, Meta-analysis, Genome-Wide Association Study/methods, Smoking/blood, Medical genetics, Female, EPIC-InterAct Consortium, Life Sciences & Biomedicine, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Adult, Metaanalysi, Understanding Society Scientific Group, medicine.medical_specialty, MESH: Smoking, Adolescent, Genomics, COGENT-Kidney Consortium, Biology, Nicotine metabolism, Risk loci, Metaanalysis, Cigarettes, Article, Young Adult, 03 medical and health sciences, genomics, medicine, Humans, Linkage Disequilibrium/genetics, Life Style, Aged, 030304 developmental biology, MESH: Adolescent, Science & Technology, MESH: Humans, Lipids/blood, MESH: Adult, 06 Biological Sciences, MESH: Lipids, MESH: Male, cardiovascular diseases, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, genome-wide association studies, MESH: Genome-Wide Association Study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

The concentrations of high- and low-density lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 novel loci, some of which were detected only because the association differed by smoking status. Additionally, we demonstrated the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings., Editorial summary: A multi-ancestry genome-wide gene-smoking interaction study identifies 13 new loci associated with serum lipids.

Published
2019

69. シュッサン・イクジ ガ ジョセイ ノ シュウギョウ ニ アタエル エイキョウ : セイベツ センコウ・カイゴ・カゾク カンケイ ノ カンテン カラ

Author

McKenzie, Colin and Leucharusmee, Supanika

Subjects
労働経済学,出産,介護,育児,女性の就業
Abstract

第一に、第一子に関して日本の母が育児休業から仕事に早く復帰する (育休休業期間をフルに活用しないこと) と、長期的に (10年後) フルタイムで働く確率があがるが、短期的に (3年後) 上がらないことが判明した。第二に、日本において末っ子の子どもの性別の性別が母親の就労に影響を与えないようである。それに対してタイにおいて就労 (労働市場参加、労働時間や賃金) に影響を与え、その影響が子供の年齢に依存する。第三に、日本の夫婦にとって将来に親又は義親を介護する確率が上がると、1946年以降に生まれた親は子供を産まない傾向が強くなるが、それ以前のコホート世帯では影響がなさそうである。 Mothers who return to work early after having their first child are found to have a higher probability of being employed full-time in the long-term (10 years later), but not in the short-term (3 years later). It is found that the gender of the youngest child has no impact on the labour market activities (labour market participation, hours worked or wage rate) of Japanese mothers. In contrast, in Thailand the gender of the youngest child has no impact on the labour market activities and that impact varies with the age of the child. For Japanese couples, an increase in the future probability of looking after their parents or parents in law leads to an increase proportion of couples born after 1946 choosing to have no children. Once a couple chooses to have at least one child, this probability has no impact. For the cohort born before 1946, there appears to be no impact., 研究種目 : 基盤研究 (B) (一般) 研究期間 : 2015～2019 課題番号 : 15H03363 研究分野 : 計量経済学

Published
2019

72. A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Author

Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., Morrison, Alanna C., Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., and Morrison, Alanna C.

Abstract

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

Published
2019
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73. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author

de Vries, Paul S., Brown, Michael R., Bentley, Amy R., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T., Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Laguzzi, Federica, Lee, Joseph H., Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Riaz, Muhammad, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Wang, Yajuan, Ware, Erin B., Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renee, de Silva, H. Janaka, Ding, Jingzhong, Dominiczak, Anna F., Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, Grabe, Hans J., Grove, Megan L., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Howard, Barbara V., Ikram, M. Arfan, Jacobs, David R., Jr., Johnson, Craig, Jonas, Jost Bruno, Kammerer, Candace M., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Koistinen, Heikki A., Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Steve B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lemaitre, Rozenn N., Li, Yize, Liang, Jingjing, Liu, Jianjun, Liu, Kiang, Loh, Marie, Louie, Tin, Magi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Mosley, Thomas H., Jr., Mukamal, Kenneth J., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Sotoodehnia, Nona, O'Connell, Jeff R., Palmer, Nicholette D., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Reiner, Alex P., Rice, Treva K., Rich, Stephen S., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tan, Nicholas, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., van Heemst, Diana, Vuckovic, Dragana, Waldenberger, Melanie, Wang, Lihua, Wang, Yujie, Wang, Zhe, Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Leander, Karin, Lehtimaki, Terho, Magnusson, Patrik K. E., Penninx, Brenda, Pereira, Alexandre C., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Zheng, Wei, Elliott, Paul, North, Kari E., Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Liu, Ching-Ti, Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Kardia, Sharon L. R., Zhu, Xiaofeng, Rotimi, Charles N., Mook-Kanamori, Dennis O., Fornage, Myriam, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Liu, Jingmin, Rotter, Jerome I., Gauderman, W. James, Province, Michael A., Munroe, Patricia B., Rice, Kenneth, Chasman, Daniel I., Cupples, L. Adrienne, Rao, Dabeeru C., Morrison, Alanna C., de Vries, Paul S., Brown, Michael R., Bentley, Amy R., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T., Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Laguzzi, Federica, Lee, Joseph H., Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Riaz, Muhammad, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Wang, Yajuan, Ware, Erin B., Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renee, de Silva, H. Janaka, Ding, Jingzhong, Dominiczak, Anna F., Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, Grabe, Hans J., Grove, Megan L., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Howard, Barbara V., Ikram, M. Arfan, Jacobs, David R., Jr., Johnson, Craig, Jonas, Jost Bruno, Kammerer, Candace M., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Koistinen, Heikki A., Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Steve B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lemaitre, Rozenn N., Li, Yize, Liang, Jingjing, Liu, Jianjun, Liu, Kiang, Loh, Marie, Louie, Tin, Magi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Mosley, Thomas H., Jr., Mukamal, Kenneth J., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Sotoodehnia, Nona, O'Connell, Jeff R., Palmer, Nicholette D., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Reiner, Alex P., Rice, Treva K., Rich, Stephen S., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tan, Nicholas, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., van Heemst, Diana, Vuckovic, Dragana, Waldenberger, Melanie, Wang, Lihua, Wang, Yujie, Wang, Zhe, Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Leander, Karin, Lehtimaki, Terho, Magnusson, Patrik K. E., Penninx, Brenda, Pereira, Alexandre C., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Zheng, Wei, Elliott, Paul, North, Kari E., Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Liu, Ching-Ti, Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Kardia, Sharon L. R., Zhu, Xiaofeng, Rotimi, Charles N., Mook-Kanamori, Dennis O., Fornage, Myriam, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Liu, Jingmin, Rotter, Jerome I., Gauderman, W. James, Province, Michael A., Munroe, Patricia B., Rice, Kenneth, Chasman, Daniel I., Cupples, L. Adrienne, Rao, Dabeeru C., and Morrison, Alanna C.

Abstract

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Published
2019
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74. Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Author

Bentley, Amy R., Sung, Yun J., Brown, Michael R., Winkler, Thomas W., Kraja, Aldi T., Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel, I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M., Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert, V, Tajuddin, Salman M., Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Hung, Yi-Jen, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Prins, Bram, Riaz, Muhammad, Robino, Antonietta, Said, M. Abdullah, Schupf, Nicole, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Wang, Tzung-Dau, Wang, Yajuan, Ware, Erin B., Wen, Wanqing, Xiang, Yong-Bing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Adeyemo, Adebowale, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Arzumanyan, Zorayr, Aung, Tin, Ballantyne, Christie, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Broeckel, Ulrich, Brown, Morris, Cade, Brian E., Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Christensen, Kaare, Concas, Maria Pina, Connell, John M., de las Fuentes, Lisa, de Silva, H. Janaka, de Vries, Paul S., Doumatey, Ayo, Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Floyd, James S., Forouhi, Nita G., Forrester, Terrence, Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gharib, Sina A., Gigante, Bruna, Giulianini, Franco, Grabe, Hans J., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Ikram, M. Arfan, Jia, Yucheng, Joehanes, Roby, Johnson, Craig, Jonas, Jost Bruno, Justice, Anne E., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Liang, Jingjing, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Kiang, Loh, Marie, Lohman, Kurt K., Louie, Tin, Luzzi, Anna, Magi, Reedik, Mahajan, Anubha, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Morris, Andrew P., Murray, Alison D., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., North, Kari E., O'Connell, Jeffrey R., Palmer, Nicholette D., Papanicolau, George J., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raitakari, Olli T., Reiner, Alex P., Renstrom, Frida, Rice, Treva K., Rich, Stephen S., Robinson, Jennifer G., Rose, Lynda M., Rosendaal, Frits R., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Tiemeier, Henning, Turner, Stephen T., Uitterlinden, Andre G., van Heemst, Diana, Waldenberger, Melanie, Wang, Heming, Wang, Lan, Wang, Lihua, Wei, Wen Bin, Williams, Christine A., Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Young, Kristin, Yu, Caizheng, Yuan, Jian-Min, Zhou, Jie, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Cooper, Richard S., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Juang, Jyh-Ming Jimmy, Kamatani, Yoichiro, Kammerer, Candace M., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Laurie, Cathy C., Lee, I-Te, Lehtimaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Pereira, Alexandre C., Rauramaa, Rainer, Redline, Susan, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Jun-Sing, Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zeggini, Eleftheria, Zheng, Wei, Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Mook-Kanamori, Dennis O., Fornage, Myriam, Province, Michael A., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Franceschini, Nora, Rotter, Jerome, I, Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Rao, Dabeeru C., Rotimi, Charles N., Cupples, L. Adrienne, Bentley, Amy R., Sung, Yun J., Brown, Michael R., Winkler, Thomas W., Kraja, Aldi T., Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel, I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M., Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert, V, Tajuddin, Salman M., Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Hung, Yi-Jen, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Prins, Bram, Riaz, Muhammad, Robino, Antonietta, Said, M. Abdullah, Schupf, Nicole, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Wang, Tzung-Dau, Wang, Yajuan, Ware, Erin B., Wen, Wanqing, Xiang, Yong-Bing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Adeyemo, Adebowale, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Arzumanyan, Zorayr, Aung, Tin, Ballantyne, Christie, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Broeckel, Ulrich, Brown, Morris, Cade, Brian E., Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Christensen, Kaare, Concas, Maria Pina, Connell, John M., de las Fuentes, Lisa, de Silva, H. Janaka, de Vries, Paul S., Doumatey, Ayo, Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Floyd, James S., Forouhi, Nita G., Forrester, Terrence, Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gharib, Sina A., Gigante, Bruna, Giulianini, Franco, Grabe, Hans J., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Ikram, M. Arfan, Jia, Yucheng, Joehanes, Roby, Johnson, Craig, Jonas, Jost Bruno, Justice, Anne E., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Liang, Jingjing, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Kiang, Loh, Marie, Lohman, Kurt K., Louie, Tin, Luzzi, Anna, Magi, Reedik, Mahajan, Anubha, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Morris, Andrew P., Murray, Alison D., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., North, Kari E., O'Connell, Jeffrey R., Palmer, Nicholette D., Papanicolau, George J., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raitakari, Olli T., Reiner, Alex P., Renstrom, Frida, Rice, Treva K., Rich, Stephen S., Robinson, Jennifer G., Rose, Lynda M., Rosendaal, Frits R., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Tiemeier, Henning, Turner, Stephen T., Uitterlinden, Andre G., van Heemst, Diana, Waldenberger, Melanie, Wang, Heming, Wang, Lan, Wang, Lihua, Wei, Wen Bin, Williams, Christine A., Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Young, Kristin, Yu, Caizheng, Yuan, Jian-Min, Zhou, Jie, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Cooper, Richard S., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Juang, Jyh-Ming Jimmy, Kamatani, Yoichiro, Kammerer, Candace M., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Laurie, Cathy C., Lee, I-Te, Lehtimaki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Pereira, Alexandre C., Rauramaa, Rainer, Redline, Susan, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Jun-Sing, Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zeggini, Eleftheria, Zheng, Wei, Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Mook-Kanamori, Dennis O., Fornage, Myriam, Province, Michael A., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Franceschini, Nora, Rotter, Jerome, I, Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Rao, Dabeeru C., Rotimi, Charles N., and Cupples, L. Adrienne

Abstract

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

Published
2019
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82. North Korea: Editors’ Overview

Author

Ito, Takatoshi, primary, Iwata, Kazumasa, additional, Lee, Jong‐Wha, additional, McKenzie, Colin, additional, Noland, Marcus, additional, and Urata, Shujiro, additional

Published
2019
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87. A genome-wide search replicates evidence of a quantitative trait locus for circulating angiotensin I-converting enzyme (ACE) unlinked to the ACE gene

Author

Adeyemo Adebowale A, Luke Amy, Forrester Terrence E, Zhu Xiaofeng, McKenzie Colin A, Bouzekri Nourdine, and Cooper Richard S

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Angiotensin I-converting enzyme (ACE) plays an important role in cardiovascular homeostasis. There is evidence from different ethnic groups that circulating ACE levels are influenced by a quantitative trait locus (QTL) at the ACE gene on chromosome 17. The finding of significant residual familial correlations in different ethnic groups, after accounting for this QTL, and the finding of support for linkage to a locus on chromosome 4 in Mexican-American families strongly suggest that there may well be QTLs for ACE unlinked to the ACE gene. Methods A genome-wide panel of microsatellite markers, and a panel of biallelic polymorphisms in the ACE gene were typed in Nigerian families. Single locus models with fixed parameters were used to test for linkage to circulating ACE with and without adjustment for the effects of the ACE gene polymorphisms. Results Strong evidence was found for D17S2193 (Zmax = 3.5); other nearby markers on chromosome 17 also showed modest support. After adjustment for the effects of the ACE gene locus, evidence of "suggestive linkage" to circulating ACE was found for D4S1629 (Zmax = 2.2); this marker is very close to a locus previously shown to be linked to circulating ACE levels in Mexican-American families. Conclusion In this report we have provided further support for the notion that there are QTLs for ACE unlinked to the ACE gene; our findings for chromosome 4, which appear to replicate the findings of a previous independent study, should be considered strong grounds for a more detailed examination of this region in the search for genes/variants which influence ACE levels. The poor yields, thus far, in defining the genetic determinants of hypertension risk suggest a need to look beyond simple relationships between genotypes and the ultimate phenotype. In addition to incorporating information on important environmental exposures, a better understanding of the factors which influence the building blocks of the blood pressure homeostatic network is also required. Detailed studies of the genetic determinants of ACE, an important component of the renin-angiotensin system, have the potential to contribute to this strategic objective.

Published
2008
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89. Classical sickle beta-globin haplotypes exhibit a high degree of long-range haplotype similarity in African and Afro-Caribbean populations

Author

Jallow Muminatou, Pinder Margaret, Rockett Kirk, Trafford Clare, Elzein Abier, Hanchard Neil, Harding Rosalind, Kwiatkowski Dominic, and McKenzie Colin

Subjects
Genetics, QH426-470
Abstract

Abstract Background The sickle (βs) mutation in the beta-globin gene (HBB) occurs on five "classical" βs haplotype backgrounds in ethnic groups of African ancestry. Strong selection in favour of the βs allele – a consequence of protection from severe malarial infection afforded by heterozygotes – has been associated with a high degree of extended haplotype similarity. The relationship between classical βs haplotypes and long-range haplotype similarity may have both anthropological and clinical implications, but to date has not been explored. Here we evaluate the haplotype similarity of classical βs haplotypes over 400 kb in population samples from Jamaica, The Gambia, and among the Yoruba of Nigeria (Hapmap YRI). Results The most common βs sub-haplotype among Jamaicans and the Yoruba was the Benin haplotype, while in The Gambia the Senegal haplotype was observed most commonly. Both subtypes exhibited a high degree of long-range haplotype similarity extending across approximately 400 kb in all three populations. This long-range similarity was significantly greater than that seen for other haplotypes sampled in these populations (P < 0.001), and was independent of marker choice and marker density. Among the Yoruba, Benin haplotypes were highly conserved, with very strong linkage disequilibrium (LD) extending a megabase across the βs mutation. Conclusion Two different classical βs haplotypes, sampled from different populations, exhibit comparable and extensive long-range haplotype similarity and strong LD. This LD extends across the adjacent recombination hotspot, and is discernable at distances in excess of 400 kb. Although the multi-centric geographic distribution of βs haplotypes indicates strong subdivision among early Holocene sub-Saharan populations, we find no evidence that selective pressures imposed by falciparum malaria varied in intensity or timing between these subpopulations. Our observations also suggest that cis-acting loci, which may influence outcomes in sickle cell disease, could lie considerable distances away from β-globin.

Published
2007
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90. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author

Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuhnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L., Canouil, Mickael, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, Fuentes, Lisa de las, de Mutsert, Renee, de Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelos, Fau, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charles, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Magi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, NelsonNona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thomas, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, Andre G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Bin Wei, Wen, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltan, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimaki, Terho, Study, Lifelines Cohort, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Poiasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Gauderman, W. James, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charles, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., Levy, Daniel, Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuhnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L., Canouil, Mickael, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, Fuentes, Lisa de las, de Mutsert, Renee, de Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelos, Fau, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charles, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Krieger, Jose E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Magi, Reedik, McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, NelsonNona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thomas, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, Andre G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Bin Wei, Wen, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltan, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimaki, Terho, Study, Lifelines Cohort, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Poiasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Gauderman, W. James, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charles, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., and Levy, Daniel

Abstract

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Published
2018
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91. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Author

Sung, Yun J., Winkler, Thomas W., de las Fuentes, Lisa, Bentley, Amy R., Brown, Michael R., Kraja, Aldi T., Schwander, Karen, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Kilpelainen, Tuomas O., Richard, Melissa A., Noordam, Raymond, Aslibekyan, Stella, Aschard, Hugues, Bartz, Traci M., Dorajoo, Rajkumar, Liu, Yongmei, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Warren, Helen R., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando Pires, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Kuhnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian' an, McKenzie, Colin A., Meian, He, Nelson, Christopher P., Rauramaa, Rainer, Schupf, Nicole, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan, Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cabrera, Claudia P., Cade, Brian, Caizheng, Yu, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Chauhan, Ganesh, Christensen, Kaare, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Debette, Stephanie, Dorr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Fisher, Virginia A., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Graff, Misa, Gu, C. Charles, Gu, Dongfeng, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hofman, Albert, Howard, Barbara V., Hunt, Steven, Irvin, Marguerite R., Jia, Yucheng, Joehanes, Roby, Justice, Anne E., Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Komulainen, Pirjo, Kooperberg, Charles, Krieger, Jose E., Kubo, Michiaki, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Kiang, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Long, Jirong, Louie, Tin, Magi, Reedik, Mahajan, Anubha, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Morris, Andrew P., Mosley, Thomas H., Jr., Munson, Peter, Murray, Alison D., Nalls, Mike A., Nasri, Ubaydah, Norris, Jill M., North, Kari, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Seshadri, Sudha, Sever, Peter, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Ultterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya X., Bin Wei, Wen, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K., Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost B., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Newman, Anne B., Oldehinkel, Albertine J., Pereira, Alexandre C., Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Kritchevsky, Stephen B., Levy, Daniel, O'Connell, Jeff R., Psaty, Bruce M., van Dam, Rob M., Sims, Mario, Arnett, Donna K., Mook-Kanamori, Dennis O., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Fornage, Myriam, Rotimi, Charles N., Province, Michael A., van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotter, Jerome I., Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Caulfield, Mark J., Elliott, Paul, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Cupples, L. Adrienne, Rao, Dabeeru C., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., de las Fuentes, Lisa, Bentley, Amy R., Brown, Michael R., Kraja, Aldi T., Schwander, Karen, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Kilpelainen, Tuomas O., Richard, Melissa A., Noordam, Raymond, Aslibekyan, Stella, Aschard, Hugues, Bartz, Traci M., Dorajoo, Rajkumar, Liu, Yongmei, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Warren, Helen R., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando Pires, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Kuhnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian' an, McKenzie, Colin A., Meian, He, Nelson, Christopher P., Rauramaa, Rainer, Schupf, Nicole, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan, Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cabrera, Claudia P., Cade, Brian, Caizheng, Yu, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Chauhan, Ganesh, Christensen, Kaare, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Debette, Stephanie, Dorr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Fisher, Virginia A., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Graff, Misa, Gu, C. Charles, Gu, Dongfeng, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hofman, Albert, Howard, Barbara V., Hunt, Steven, Irvin, Marguerite R., Jia, Yucheng, Joehanes, Roby, Justice, Anne E., Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Komulainen, Pirjo, Kooperberg, Charles, Krieger, Jose E., Kubo, Michiaki, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Kiang, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Long, Jirong, Louie, Tin, Magi, Reedik, Mahajan, Anubha, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Morris, Andrew P., Mosley, Thomas H., Jr., Munson, Peter, Murray, Alison D., Nalls, Mike A., Nasri, Ubaydah, Norris, Jill M., North, Kari, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Seshadri, Sudha, Sever, Peter, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Ultterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya X., Bin Wei, Wen, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K., Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost B., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Newman, Anne B., Oldehinkel, Albertine J., Pereira, Alexandre C., Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Kritchevsky, Stephen B., Levy, Daniel, O'Connell, Jeff R., Psaty, Bruce M., van Dam, Rob M., Sims, Mario, Arnett, Donna K., Mook-Kanamori, Dennis O., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Fornage, Myriam, Rotimi, Charles N., Province, Michael A., van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotter, Jerome I., Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Caulfield, Mark J., Elliott, Paul, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Cupples, L. Adrienne, Rao, Dabeeru C., and Chasman, Daniel I.

Abstract

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2).

Published
2018
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95. Correction: Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

Author

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

Published
2018
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96. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Author

Sung, Yun J., primary, Winkler, Thomas W., additional, de las Fuentes, Lisa, additional, Bentley, Amy R., additional, Brown, Michael R., additional, Kraja, Aldi T., additional, Schwander, Karen, additional, Ntalla, Ioanna, additional, Guo, Xiuqing, additional, Franceschini, Nora, additional, Lu, Yingchang, additional, Cheng, Ching-Yu, additional, Sim, Xueling, additional, Vojinovic, Dina, additional, Marten, Jonathan, additional, Musani, Solomon K., additional, Li, Changwei, additional, Feitosa, Mary F., additional, Kilpeläinen, Tuomas O., additional, Richard, Melissa A., additional, Noordam, Raymond, additional, Aslibekyan, Stella, additional, Aschard, Hugues, additional, Bartz, Traci M., additional, Dorajoo, Rajkumar, additional, Liu, Yongmei, additional, Manning, Alisa K., additional, Rankinen, Tuomo, additional, Smith, Albert Vernon, additional, Tajuddin, Salman M., additional, Tayo, Bamidele O., additional, Warren, Helen R., additional, Zhao, Wei, additional, Zhou, Yanhua, additional, Matoba, Nana, additional, Sofer, Tamar, additional, Alver, Maris, additional, Amini, Marzyeh, additional, Boissel, Mathilde, additional, Chai, Jin Fang, additional, Chen, Xu, additional, Divers, Jasmin, additional, Gandin, Ilaria, additional, Gao, Chuan, additional, Giulianini, Franco, additional, Goel, Anuj, additional, Harris, Sarah E., additional, Hartwig, Fernando Pires, additional, Horimoto, Andrea R.V.R., additional, Hsu, Fang-Chi, additional, Jackson, Anne U., additional, Kähönen, Mika, additional, Kasturiratne, Anuradhani, additional, Kühnel, Brigitte, additional, Leander, Karin, additional, Lee, Wen-Jane, additional, Lin, Keng-Hung, additional, ’an Luan, Jian, additional, McKenzie, Colin A., additional, Meian, He, additional, Nelson, Christopher P., additional, Rauramaa, Rainer, additional, Schupf, Nicole, additional, Scott, Robert A., additional, Sheu, Wayne H.H., additional, Stančáková, Alena, additional, Takeuchi, Fumihiko, additional, van der Most, Peter J., additional, Varga, Tibor V., additional, Wang, Heming, additional, Wang, Yajuan, additional, Ware, Erin B., additional, Weiss, Stefan, additional, Wen, Wanqing, additional, Yanek, Lisa R., additional, Zhang, Weihua, additional, Zhao, Jing Hua, additional, Afaq, Saima, additional, Alfred, Tamuno, additional, Amin, Najaf, additional, Arking, Dan, additional, Aung, Tin, additional, Barr, R. Graham, additional, Bielak, Lawrence F., additional, Boerwinkle, Eric, additional, Bottinger, Erwin P., additional, Braund, Peter S., additional, Brody, Jennifer A., additional, Broeckel, Ulrich, additional, Cabrera, Claudia P., additional, Cade, Brian, additional, Caizheng, Yu, additional, Campbell, Archie, additional, Canouil, Mickaël, additional, Chakravarti, Aravinda, additional, Chauhan, Ganesh, additional, Christensen, Kaare, additional, Cocca, Massimiliano, additional, Collins, Francis S., additional, Connell, John M., additional, de Mutsert, Renée, additional, de Silva, H. Janaka, additional, Debette, Stephanie, additional, Dörr, Marcus, additional, Duan, Qing, additional, Eaton, Charles B., additional, Ehret, Georg, additional, Evangelou, Evangelos, additional, Faul, Jessica D., additional, Fisher, Virginia A., additional, Forouhi, Nita G., additional, Franco, Oscar H., additional, Friedlander, Yechiel, additional, Gao, He, additional, Gigante, Bruna, additional, Graff, Misa, additional, Gu, C. Charles, additional, Gu, Dongfeng, additional, Gupta, Preeti, additional, Hagenaars, Saskia P., additional, Harris, Tamara B., additional, He, Jiang, additional, Heikkinen, Sami, additional, Heng, Chew-Kiat, additional, Hirata, Makoto, additional, Hofman, Albert, additional, Howard, Barbara V., additional, Hunt, Steven, additional, Irvin, Marguerite R., additional, Jia, Yucheng, additional, Joehanes, Roby, additional, Justice, Anne E., additional, Katsuya, Tomohiro, additional, Kaufman, Joel, additional, Kerrison, Nicola D., additional, Khor, Chiea Chuen, additional, Koh, Woon-Puay, additional, Koistinen, Heikki A., additional, Komulainen, Pirjo, additional, Kooperberg, Charles, additional, Krieger, Jose E., additional, Kubo, Michiaki, additional, Kuusisto, Johanna, additional, Langefeld, Carl D., additional, Langenberg, Claudia, additional, Launer, Lenore J., additional, Lehne, Benjamin, additional, Lewis, Cora E., additional, Li, Yize, additional, Lim, Sing Hui, additional, Lin, Shiow, additional, Liu, Ching-Ti, additional, Liu, Jianjun, additional, Liu, Jingmin, additional, Liu, Kiang, additional, Liu, Yeheng, additional, Loh, Marie, additional, Lohman, Kurt K., additional, Long, Jirong, additional, Louie, Tin, additional, Mägi, Reedik, additional, Mahajan, Anubha, additional, Meitinger, Thomas, additional, Metspalu, Andres, additional, Milani, Lili, additional, Momozawa, Yukihide, additional, Morris, Andrew P., additional, Mosley, Thomas H., additional, Munson, Peter, additional, Murray, Alison D., additional, Nalls, Mike A., additional, Nasri, Ubaydah, additional, Norris, Jill M., additional, North, Kari, additional, Ogunniyi, Adesola, additional, Padmanabhan, Sandosh, additional, Palmas, Walter R., additional, Palmer, Nicholette D., additional, Pankow, James S., additional, Pedersen, Nancy L., additional, Peters, Annette, additional, Peyser, Patricia A., additional, Polasek, Ozren, additional, Raitakari, Olli T., additional, Renström, Frida, additional, Rice, Treva K., additional, Ridker, Paul M., additional, Robino, Antonietta, additional, Robinson, Jennifer G., additional, Rose, Lynda M., additional, Rudan, Igor, additional, Sabanayagam, Charumathi, additional, Salako, Babatunde L., additional, Sandow, Kevin, additional, Schmidt, Carsten O., additional, Schreiner, Pamela J., additional, Scott, William R., additional, Seshadri, Sudha, additional, Sever, Peter, additional, Sitlani, Colleen M., additional, Smith, Jennifer A., additional, Snieder, Harold, additional, Starr, John M., additional, Strauch, Konstantin, additional, Tang, Hua, additional, Taylor, Kent D., additional, Teo, Yik Ying, additional, Tham, Yih Chung, additional, Uitterlinden, André G., additional, Waldenberger, Melanie, additional, Wang, Lihua, additional, Wang, Ya X., additional, Wei, Wen Bin, additional, Williams, Christine, additional, Wilson, Gregory, additional, Wojczynski, Mary K., additional, Yao, Jie, additional, Yuan, Jian-Min, additional, Zonderman, Alan B., additional, Becker, Diane M., additional, Boehnke, Michael, additional, Bowden, Donald W., additional, Chambers, John C., additional, Chen, Yii-Der Ida, additional, de Faire, Ulf, additional, Deary, Ian J., additional, Esko, Tõnu, additional, Farrall, Martin, additional, Forrester, Terrence, additional, Franks, Paul W., additional, Freedman, Barry I., additional, Froguel, Philippe, additional, Gasparini, Paolo, additional, Gieger, Christian, additional, Horta, Bernardo Lessa, additional, Hung, Yi-Jen, additional, Jonas, Jost B., additional, Kato, Norihiro, additional, Kooner, Jaspal S., additional, Laakso, Markku, additional, Lehtimäki, Terho, additional, Liang, Kae-Woei, additional, Magnusson, Patrik K.E., additional, Newman, Anne B., additional, Oldehinkel, Albertine J., additional, Pereira, Alexandre C., additional, Redline, Susan, additional, Rettig, Rainer, additional, Samani, Nilesh J., additional, Scott, James, additional, Shu, Xiao-Ou, additional, van der Harst, Pim, additional, Wagenknecht, Lynne E., additional, Wareham, Nicholas J., additional, Watkins, Hugh, additional, Weir, David R., additional, Wickremasinghe, Ananda R., additional, Wu, Tangchun, additional, Zheng, Wei, additional, Kamatani, Yoichiro, additional, Laurie, Cathy C., additional, Bouchard, Claude, additional, Cooper, Richard S., additional, Evans, Michele K., additional, Gudnason, Vilmundur, additional, Kardia, Sharon L.R., additional, Kritchevsky, Stephen B., additional, Levy, Daniel, additional, O’Connell, Jeff R., additional, Psaty, Bruce M., additional, van Dam, Rob M., additional, Sims, Mario, additional, Arnett, Donna K., additional, Mook-Kanamori, Dennis O., additional, Kelly, Tanika N., additional, Fox, Ervin R., additional, Hayward, Caroline, additional, Fornage, Myriam, additional, Rotimi, Charles N., additional, Province, Michael A., additional, van Duijn, Cornelia M., additional, Tai, E. Shyong, additional, Wong, Tien Yin, additional, Loos, Ruth J.F., additional, Reiner, Alex P., additional, Rotter, Jerome I., additional, Zhu, Xiaofeng, additional, Bierut, Laura J., additional, Gauderman, W. James, additional, Caulfield, Mark J., additional, Elliott, Paul, additional, Rice, Kenneth, additional, Munroe, Patricia B., additional, Morrison, Alanna C., additional, Cupples, L. Adrienne, additional, Rao, Dabeeru C., additional, and Chasman, Daniel I., additional

Published
2018
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100. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, 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Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, and Cupples, L Adrienne

Abstract

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

Published
2017
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