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Common Variants Associated with Plasma Triglycerides and Risk for Coronary Artery Disease

Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayse; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tonu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkila, Kauko; Hypponen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikainen, Leo-Pekka; Magnusson, Patrik K. E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Muller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Ines; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L.; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S. F.; Doring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Goran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J. P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimaki, Terho; Lin, Shih-Yi; Lindstrom, Jaana; Loos, Ruth J. F.; Mach, Francois; McArdle, Wendy L.; Meisinger, Christa; Mitchell, Braxton D.; Muller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V. M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stancakova, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrieres, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Jarvelin, Marjo-Riitta; Jula, Antti; Kahonen, Mika; Kaprio, Jaakko; Kesaniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; Marz, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njolstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E. H.; Sheu, Wayne H. H.; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H. R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N. A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.; Ripatti, Samuli; Cupples, L. Adrienne; Sandhu, Manjinder S.; Rich, Stephen S.; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L.; Ingelsson, Erik; Abecasis, Goncalo R.; Daly, Mark J.; Neale, Benjamin M.; & Kathiresan, Sekar. (2013). Common Variants Associated with Plasma Triglycerides and Risk for Coronary Artery Disease. Nature Genetics, 45(11), 1345-52.

Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayse; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tonu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkila, Kauko; Hypponen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikainen, Leo-Pekka; Magnusson, Patrik K. E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Muller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Ines; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L.; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S. F.; Doring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Goran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J. P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimaki, Terho; Lin, Shih-Yi; Lindstrom, Jaana; Loos, Ruth J. F.; Mach, Francois; McArdle, Wendy L.; Meisinger, Christa; Mitchell, Braxton D.; Muller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V. M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stancakova, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrieres, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Jarvelin, Marjo-Riitta; Jula, Antti; Kahonen, Mika; Kaprio, Jaakko; Kesaniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; Marz, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njolstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E. H.; Sheu, Wayne H. H.; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H. R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N. A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.; Ripatti, Samuli; Cupples, L. Adrienne; Sandhu, Manjinder S.; Rich, Stephen S.; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L.; Ingelsson, Erik; Abecasis, Goncalo R.; Daly, Mark J.; Neale, Benjamin M.; & Kathiresan, Sekar. (2013). Common Variants Associated with Plasma Triglycerides and Risk for Coronary Artery Disease. Nature Genetics, 45(11), 1345-52.

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Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10−8 for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.




JOUR



Do, Ron
Willer, Cristen J.
Schmidt, Ellen M.
Sengupta, Sebanti
Gao, Chi
Peloso, Gina M.
Gustafsson, Stefan
Kanoni, Stavroula
Ganna, Andrea
Chen, Jin
Buchkovich, Martin L.
Mora, Samia
Beckmann, Jacques S.
Bragg-Gresham, Jennifer L.
Chang, Hsing-Yi
Demirkan, Ayse
Den Hertog, Heleen M.
Donnelly, Louise A.
Ehret, Georg B.
Esko, Tonu
Feitosa, Mary F.
Ferreira, Teresa
Fischer, Krista
Fontanillas, Pierre
Fraser, Ross M.
Freitag, Daniel F.
Gurdasani, Deepti
Heikkila, Kauko
Hypponen, Elina
Isaacs, Aaron
Jackson, Anne U.
Johansson, Asa
Johnson, Toby
Kaakinen, Marika
Kettunen, Johannes
Kleber, Marcus E.
Li, Xiaohui
Luan, Jian'an
Lyytikainen, Leo-Pekka
Magnusson, Patrik K. E.
Mangino, Massimo
Mihailov, Evelin
Montasser, May E.
Muller-Nurasyid, Martina
Nolte, Ilja M.
O'Connell, Jeffrey R.
Palmer, Cameron D.
Perola, Markus
Petersen, Ann-Kristin
Sanna, Serena
Saxena, Richa
Service, Susan K.
Shah, Sonia
Shungin, Dmitry
Sidore, Carlo
Song, Ci
Strawbridge, Rona J.
Surakka, Ida
Tanaka, Toshiko
Teslovich, Tanya M.
Thorleifsson, Gudmar
Van den Herik, Evita G.
Voight, Benjamin F.
Volcik, Kelly A.
Waite, Lindsay L.
Wong, Andrew
Wu, Ying
Zhang, Weihua
Absher, Devin
Asiki, Gershim
Barroso, Ines
Been, Latonya F.
Bolton, Jennifer L.
Bonnycastle, Lori L.
Brambilla, Paolo
Burnett, Mary S.
Cesana, Giancarlo
Dimitriou, Maria
Doney, Alex S. F.
Doring, Angela
Elliott, Paul
Epstein, Stephen E.
Eyjolfsson, Gudmundur Ingi
Gigante, Bruna
Goodarzi, Mark O.
Grallert, Harald
Gravito, Martha L.
Groves, Christopher J.
Hallmans, Goran
Hartikainen, Anna-Liisa
Hayward, Caroline
Hernandez, Dena
Hicks, Andrew A.
Holm, Hilma
Hung, Yi-Jen
Illig, Thomas
Jones, Michelle R.
Kaleebu, Pontiano
Kastelein, John J. P.
Khaw, Kay-Tee
Kim, Eric
Klopp, Norman
Komulainen, Pirjo
Kumari, Meena
Langenberg, Claudia
Lehtimaki, Terho
Lin, Shih-Yi
Lindstrom, Jaana
Loos, Ruth J. F.
Mach, Francois
McArdle, Wendy L.
Meisinger, Christa
Mitchell, Braxton D.
Muller, Gabrielle
Nagaraja, Ramaiah
Narisu, Narisu
Nieminen, Tuomo V. M.
Nsubuga, Rebecca N.
Olafsson, Isleifur
Ong, Ken K.
Palotie, Aarno
Papamarkou, Theodore
Pomilla, Cristina
Pouta, Anneli
Rader, Daniel J.
Reilly, Muredach P.
Ridker, Paul M.
Rivadeneira, Fernando
Rudan, Igor
Ruokonen, Aimo
Samani, Nilesh
Scharnagl, Hubert
Seeley, Janet
Silander, Kaisa
Stancakova, Alena
Stirrups, Kathleen
Swift, Amy J.
Tiret, Laurence
Uitterlinden, Andre G.
van Pelt, L. Joost
Vedantam, Sailaja
Wainwright, Nicholas
Wijmenga, Cisca
Wild, Sarah H.
Willemsen, Gonneke
Wilsgaard, Tom
Wilson, James F.
Young, Elizabeth H.
Zhao, Jing Hua
Adair, Linda S.
Arveiler, Dominique
Assimes, Themistocles L.
Bandinelli, Stefania
Bennett, Franklyn
Bochud, Murielle
Boehm, Bernhard O.
Boomsma, Dorret I.
Borecki, Ingrid B.
Bornstein, Stefan R.
Bovet, Pascal
Burnier, Michel
Campbell, Harry
Chakravarti, Aravinda
Chambers, John C.
Chen, Yii-Der Ida
Collins, Francis S.
Cooper, Richard S.
Danesh, John
Dedoussis, George
de Faire, Ulf
Feranil, Alan B.
Ferrieres, Jean
Ferrucci, Luigi
Freimer, Nelson B.
Gieger, Christian
Groop, Leif C.
Gudnason, Vilmundur
Gyllensten, Ulf
Hamsten, Anders
Harris, Tamara B.
Hingorani, Aroon
Hirschhorn, Joel N.
Hofman, Albert
Hovingh, G. Kees
Hsiung, Chao Agnes
Humphries, Steve E.
Hunt, Steven C.
Hveem, Kristian
Iribarren, Carlos
Jarvelin, Marjo-Riitta
Jula, Antti
Kahonen, Mika
Kaprio, Jaakko
Kesaniemi, Antero
Kivimaki, Mika
Kooner, Jaspal S.
Koudstaal, Peter J.
Krauss, Ronald M.
Kuh, Diana
Kuusisto, Johanna
Kyvik, Kirsten O.
Laakso, Markku
Lakka, Timo A.
Lind, Lars
Lindgren, Cecilia M.
Martin, Nicholas G.
Marz, Winfried
McCarthy, Mark I.
McKenzie, Colin A.
Meneton, Pierre
Metspalu, Andres
Moilanen, Leena
Morris, Andrew D.
Munroe, Patricia B.
Njolstad, Inger
Pedersen, Nancy L.
Power, Chris
Pramstaller, Peter P.
Price, Jackie F.
Psaty, Bruce M.
Quertermous, Thomas
Rauramaa, Rainer
Saleheen, Danish
Salomaa, Veikko
Sanghera, Dharambir K.
Saramies, Jouko
Schwarz, Peter E. H.
Sheu, Wayne H. H.
Shuldiner, Alan R.
Siegbahn, Agneta
Spector, Tim D.
Stefansson, Kari
Strachan, David P.
Tayo, Bamidele O.
Tremoli, Elena
Tuomilehto, Jaakko
Uusitupa, Matti
van Duijn, Cornelia M.
Vollenweider, Peter
Wallentin, Lars
Wareham, Nicholas J.
Whitfield, John B.
Wolffenbuttel, Bruce H. R.
Altshuler, David
Ordovas, Jose M.
Boerwinkle, Eric
Palmer, Colin N. A.
Thorsteinsdottir, Unnur
Chasman, Daniel I.
Rotter, Jerome I.
Franks, Paul W.
Ripatti, Samuli
Cupples, L. Adrienne
Sandhu, Manjinder S.
Rich, Stephen S.
Boehnke, Michael
Deloukas, Panos
Mohlke, Karen L.
Ingelsson, Erik
Abecasis, Goncalo R.
Daly, Mark J.
Neale, Benjamin M.
Kathiresan, Sekar



2013


Nature Genetics

45

11

1345-52










206