Standard
Exome-wide association study of plasma lipids in >300,000 individuals. / Liu, Dajiang J.; Peloso, Gina M.; Yu, Haojie; Butterworth, Adam S.; Wang, Xiao; Mahajan, Anubha; Saleheen, Danish; Emdin, Connor; Alam, Dewan; Alves, Alexessander Couto; Amouyel, Philippe; Angelantonio, Emanuele DI; Arveiler, Dominique; Assimes, Themistocles L.; Auer, Paul L.; Baber, Usman; Ballantyne, Christie M.; Bang, Lia E.; Benn, Marianne; Bis, Joshua C.; Boehnke, Michael; Boerwinkle, Eric; Bork-Jensen, Jette; Bottinger, Erwin P.; Brandslund, Ivan; Brown, Morris; Busonero, Fabio; Caulfield, Mark J.; Chambers, John C.; Chasman, Daniel I.; Chen, Y. Eugene; Chen, Yii Der Ida; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y.; Connell, John M.; Cucca, Francesco; Cupples, L. Adrienne; Damrauer, Scott M.; Davies, Gail; Deary, Ian J.; Dedoussis, George; Denny, Joshua C.; Dominiczak, Anna; Dubé, Marie Pierre; Ebeling, Tapani; Eiriksdottir, Gudny; Esko, Toñu; Farmaki, Aliki Eleni; Feitosa, Mary F.; Ferrario, Marco; Ferrieres, Jean; Ford, Ian; Fornage, Myriam; Franks, Paul W.; Frayling, Timothy M.; Frikke-Schmidt, Ruth; Fritsche, Lars G.; Frossard, Philippe; Fuster, Valentin; Ganesh, Santhi K.; Gao, Wei; Garcia, Melissa E.; Gieger, Christian; Giulianini, Franco; Goodarzi, Mark O.; Grallert, Harald; Grarup, Niels; Groop, Leif; Grove, Megan L.; Gudnason, Vilmundur; Hansen, Torben; Harris, Tamara B.; Hayward, Caroline; Hirschhorn, Joel N.; Holmen, Oddgeir L.; Huffman, Jennifer; Huo, Yong; Hveem, Kristian; Jabeen, Sehrish; Jackson, Anne U.; Jakobsdottir, Johanna; Jarvelin, Marjo Riitta; Jensen, Gorm B.; Jørgensen, Marit E.; Jukema, J. Wouter; Justesen, Johanne M.; Kamstrup, Pia R.; Kanoni, Stavroula; Karpe, Fredrik; Kee, Frank; Khera, Amit V.; Klarin, Derek; Koistinen, Heikki A.; Kooner, Jaspal S.; Kooperberg, Charles; Kuulasmaa, Kari; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo; Langenberg, Claudia; Langsted, Anne; Launer, Lenore J.; Lauritzen, Torsten; MLiewald, David C.; Lin, Li An; Linneberg, Allan; Loos, Ruth J.F.; Lu, Yingchang; Lu, Xiangfeng; Mägi, Reedik; Malarstig, Anders; Manichaikul, Ani; Manning, Alisa K.; Mäntyselkä, Pekka; Marouli, Eirini; Masca, Nicholas G.D.; Maschio, Andrea; Meigs, James B.; Melander, Olle; Metspalu, Andres; Morris, Andrew P.; Morrison, Alanna C.; Mulas, Antonella; Müller-Nurasyid, Martina; Munroe, Patricia B.; Neville, Matt J.; Nielsen, Sune F.; Nielsen, Jonas B.; Nordestgaard, Børge G.; Ordovas, Jose M.; Mehran, Roxana; O'Donnell, Christoper J.; Orho-Melander, Marju; Molony, Cliona M.; Muntendam, Pieter; Padmanabhan, Sandosh; Palmer, Colin N.A.; Pasko, Dorota; Patel, Aniruddh P.; Pedersen, Oluf; Perola, Markus; Peters, Annette; Pisinger, Charlotta; Pistis, Giorgio; Polasek, Ozren; Poulter, Neil; Psaty, Bruce M.; Rader, Daniel J.; Rasheed, Asif; Rauramaa, Rainer; Reilly, Dermot F.; Reiner, Alex P.; Renström, Frida; Rich, Stephen S.; Ridker, Paul M.; Rioux, John D.; Robertson, Neil R.; Roden, Dan M.; Rotter, Jerome I.; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J.; Sanna, Serena; Sattar, Naveed; Schmidt, Ellen M.; Scott, Robert A.; Sever, Peter; Sevilla, Raquel S.; Shaffer, Christian M.; Sim, Xueling; Sivapalaratnam, Suthesh; Small, Kerrin S.; Smith, Albert V.; Smith, Blair H.; Somayajula, Sangeetha; Southam, Lorraine; Spector, Timothy D.; Speliotes, Elizabeth K.; Starr, John M.; Stirrups, Kathleen E.; Stitziel, Nathan; Strauch, Konstantin; Stringham, Heather M.; Surendran, Praveen; Tada, Hayato; Tall, Alan R.; Tang, Hua; Tardif, Jean Claude; Taylor, Kent D.; Trompet, Stella; Tsao, Philip S.; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Zuydam, Natalie R.Van; Varbo, Anette; Varga, Tibor V.; Virtamo, Jarmo; Waldenberger, Melanie; Wang, Nan; Wareham, Nick J.; Warren, Helen R.; Weeke, Peter E.; Weinstock, Joshua; Wessel, Jennifer; Wilson, James G.; Wilson, Peter W.F.; Xu, Ming; Yaghootkar, Hanieh; Young, Robin; Zeggini, Eleftheria; Zhang, He; Zheng, Neil S.; Zhang, Weihua; Zhang, Yan; Zhou, Wei; Zhou, Yanhua; Zoledziewska, Magdalena; Howson, Joanna M.M.; Danesh, John; McCarthy, Mark I.; Cowan, Chad A.; Abecasis, Goncalo; Deloukas, Panos; Musunuru, Kiran; Willer, Cristen J.; Kathiresan, Sekar; V Varga, Tibor.
I:
Nature Genetics, Bind 49, Nr. 12, 01.12.2017, s. 1758-1766.
Publikation: Bidrag til tidsskrift › Letter › Forskning › fagfællebedømt
Harvard
Liu, DJ, Peloso, GM, Yu, H, Butterworth, AS, Wang, X, Mahajan, A, Saleheen, D, Emdin, C, Alam, D, Alves, AC, Amouyel, P, Angelantonio, EDI, Arveiler, D, Assimes, TL, Auer, PL, Baber, U, Ballantyne, CM, Bang, LE
, Benn, M, Bis, JC, Boehnke, M, Boerwinkle, E, Bork-Jensen, J, Bottinger, EP, Brandslund, I, Brown, M, Busonero, F, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, YE, Chen, YDI, Chowdhury, R, Christensen, C, Chu, AY, Connell, JM, Cucca, F, Cupples, LA, Damrauer, SM, Davies, G, Deary, IJ, Dedoussis, G, Denny, JC, Dominiczak, A, Dubé, MP, Ebeling, T, Eiriksdottir, G, Esko, T, Farmaki, AE, Feitosa, MF, Ferrario, M, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Frayling, TM
, Frikke-Schmidt, R, Fritsche, LG, Frossard, P, Fuster, V, Ganesh, SK, Gao, W, Garcia, ME, Gieger, C, Giulianini, F, Goodarzi, MO, Grallert, H
, Grarup, N, Groop, L, Grove, ML, Gudnason, V
, Hansen, T, Harris, TB, Hayward, C, Hirschhorn, JN, Holmen, OL, Huffman, J, Huo, Y, Hveem, K, Jabeen, S, Jackson, AU, Jakobsdottir, J, Jarvelin, MR, Jensen, GB, Jørgensen, ME, Jukema, JW
, Justesen, JM, Kamstrup, PR, Kanoni, S, Karpe, F, Kee, F, Khera, AV, Klarin, D, Koistinen, HA, Kooner, JS, Kooperberg, C, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, T, Langenberg, C, Langsted, A, Launer, LJ, Lauritzen, T, MLiewald, DC, Lin, LA
, Linneberg, A, Loos, RJF, Lu, Y, Lu, X, Mägi, R, Malarstig, A, Manichaikul, A, Manning, AK, Mäntyselkä, P, Marouli, E, Masca, NGD, Maschio, A, Meigs, JB, Melander, O, Metspalu, A, Morris, AP, Morrison, AC, Mulas, A, Müller-Nurasyid, M, Munroe, PB, Neville, MJ, Nielsen, SF, Nielsen, JB
, Nordestgaard, BG, Ordovas, JM, Mehran, R, O'Donnell, CJ, Orho-Melander, M, Molony, CM, Muntendam, P, Padmanabhan, S, Palmer, CNA, Pasko, D, Patel, AP
, Pedersen, O, Perola, M, Peters, A, Pisinger, C, Pistis, G, Polasek, O, Poulter, N, Psaty, BM, Rader, DJ, Rasheed, A, Rauramaa, R, Reilly, DF, Reiner, AP, Renström, F, Rich, SS, Ridker, PM, Rioux, JD, Robertson, NR, Roden, DM, Rotter, JI, Rudan, I, Salomaa, V, Samani, NJ, Sanna, S, Sattar, N, Schmidt, EM, Scott, RA, Sever, P, Sevilla, RS, Shaffer, CM, Sim, X, Sivapalaratnam, S, Small, KS, Smith, AV, Smith, BH, Somayajula, S, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stirrups, KE, Stitziel, N, Strauch, K, Stringham, HM, Surendran, P, Tada, H, Tall, AR, Tang, H, Tardif, JC, Taylor, KD, Trompet, S, Tsao, PS, Tuomilehto, J
, Tybjaerg-Hansen, A, Zuydam, NRV, Varbo, A, Varga, TV, Virtamo, J, Waldenberger, M, Wang, N, Wareham, NJ, Warren, HR, Weeke, PE, Weinstock, J, Wessel, J, Wilson, JG, Wilson, PWF, Xu, M, Yaghootkar, H, Young, R, Zeggini, E, Zhang, H, Zheng, NS, Zhang, W, Zhang, Y, Zhou, W, Zhou, Y, Zoledziewska, M, Howson, JMM, Danesh, J, McCarthy, MI, Cowan, CA, Abecasis, G, Deloukas, P, Musunuru, K, Willer, CJ, Kathiresan, S
& V Varga, T 2017, '
Exome-wide association study of plasma lipids in >300,000 individuals',
Nature Genetics, bind 49, nr. 12, s. 1758-1766.
https://doi.org/10.1038/ng.3977APA
Liu, D. J., Peloso, G. M., Yu, H., Butterworth, A. S., Wang, X., Mahajan, A., Saleheen, D., Emdin, C., Alam, D., Alves, A. C., Amouyel, P., Angelantonio, E. DI., Arveiler, D., Assimes, T. L., Auer, P. L., Baber, U., Ballantyne, C. M., Bang, L. E.
, Benn, M., ... V Varga, T. (2017).
Exome-wide association study of plasma lipids in >300,000 individuals.
Nature Genetics,
49(12), 1758-1766.
https://doi.org/10.1038/ng.3977Vancouver
Liu DJ, Peloso GM, Yu H, Butterworth AS, Wang X, Mahajan A o.a.
Exome-wide association study of plasma lipids in >300,000 individuals.
Nature Genetics. 2017 dec. 1;49(12):1758-1766.
https://doi.org/10.1038/ng.3977Author
Liu, Dajiang J. ; Peloso, Gina M. ; Yu, Haojie ; Butterworth, Adam S. ; Wang, Xiao ; Mahajan, Anubha ; Saleheen, Danish ; Emdin, Connor ; Alam, Dewan ; Alves, Alexessander Couto ; Amouyel, Philippe ; Angelantonio, Emanuele DI ; Arveiler, Dominique ; Assimes, Themistocles L. ; Auer, Paul L. ; Baber, Usman ; Ballantyne, Christie M. ; Bang, Lia E. ; Benn, Marianne ; Bis, Joshua C. ; Boehnke, Michael ; Boerwinkle, Eric ; Bork-Jensen, Jette ; Bottinger, Erwin P. ; Brandslund, Ivan ; Brown, Morris ; Busonero, Fabio ; Caulfield, Mark J. ; Chambers, John C. ; Chasman, Daniel I. ; Chen, Y. Eugene ; Chen, Yii Der Ida ; Chowdhury, Rajiv ; Christensen, Cramer ; Chu, Audrey Y. ; Connell, John M. ; Cucca, Francesco ; Cupples, L. Adrienne ; Damrauer, Scott M. ; Davies, Gail ; Deary, Ian J. ; Dedoussis, George ; Denny, Joshua C. ; Dominiczak, Anna ; Dubé, Marie Pierre ; Ebeling, Tapani ; Eiriksdottir, Gudny ; Esko, Toñu ; Farmaki, Aliki Eleni ; Feitosa, Mary F. ; Ferrario, Marco ; Ferrieres, Jean ; Ford, Ian ; Fornage, Myriam ; Franks, Paul W. ; Frayling, Timothy M. ; Frikke-Schmidt, Ruth ; Fritsche, Lars G. ; Frossard, Philippe ; Fuster, Valentin ; Ganesh, Santhi K. ; Gao, Wei ; Garcia, Melissa E. ; Gieger, Christian ; Giulianini, Franco ; Goodarzi, Mark O. ; Grallert, Harald ; Grarup, Niels ; Groop, Leif ; Grove, Megan L. ; Gudnason, Vilmundur ; Hansen, Torben ; Harris, Tamara B. ; Hayward, Caroline ; Hirschhorn, Joel N. ; Holmen, Oddgeir L. ; Huffman, Jennifer ; Huo, Yong ; Hveem, Kristian ; Jabeen, Sehrish ; Jackson, Anne U. ; Jakobsdottir, Johanna ; Jarvelin, Marjo Riitta ; Jensen, Gorm B. ; Jørgensen, Marit E. ; Jukema, J. Wouter ; Justesen, Johanne M. ; Kamstrup, Pia R. ; Kanoni, Stavroula ; Karpe, Fredrik ; Kee, Frank ; Khera, Amit V. ; Klarin, Derek ; Koistinen, Heikki A. ; Kooner, Jaspal S. ; Kooperberg, Charles ; Kuulasmaa, Kari ; Kuusisto, Johanna ; Laakso, Markku ; Lakka, Timo ; Langenberg, Claudia ; Langsted, Anne ; Launer, Lenore J. ; Lauritzen, Torsten ; MLiewald, David C. ; Lin, Li An ; Linneberg, Allan ; Loos, Ruth J.F. ; Lu, Yingchang ; Lu, Xiangfeng ; Mägi, Reedik ; Malarstig, Anders ; Manichaikul, Ani ; Manning, Alisa K. ; Mäntyselkä, Pekka ; Marouli, Eirini ; Masca, Nicholas G.D. ; Maschio, Andrea ; Meigs, James B. ; Melander, Olle ; Metspalu, Andres ; Morris, Andrew P. ; Morrison, Alanna C. ; Mulas, Antonella ; Müller-Nurasyid, Martina ; Munroe, Patricia B. ; Neville, Matt J. ; Nielsen, Sune F. ; Nielsen, Jonas B. ; Nordestgaard, Børge G. ; Ordovas, Jose M. ; Mehran, Roxana ; O'Donnell, Christoper J. ; Orho-Melander, Marju ; Molony, Cliona M. ; Muntendam, Pieter ; Padmanabhan, Sandosh ; Palmer, Colin N.A. ; Pasko, Dorota ; Patel, Aniruddh P. ; Pedersen, Oluf ; Perola, Markus ; Peters, Annette ; Pisinger, Charlotta ; Pistis, Giorgio ; Polasek, Ozren ; Poulter, Neil ; Psaty, Bruce M. ; Rader, Daniel J. ; Rasheed, Asif ; Rauramaa, Rainer ; Reilly, Dermot F. ; Reiner, Alex P. ; Renström, Frida ; Rich, Stephen S. ; Ridker, Paul M. ; Rioux, John D. ; Robertson, Neil R. ; Roden, Dan M. ; Rotter, Jerome I. ; Rudan, Igor ; Salomaa, Veikko ; Samani, Nilesh J. ; Sanna, Serena ; Sattar, Naveed ; Schmidt, Ellen M. ; Scott, Robert A. ; Sever, Peter ; Sevilla, Raquel S. ; Shaffer, Christian M. ; Sim, Xueling ; Sivapalaratnam, Suthesh ; Small, Kerrin S. ; Smith, Albert V. ; Smith, Blair H. ; Somayajula, Sangeetha ; Southam, Lorraine ; Spector, Timothy D. ; Speliotes, Elizabeth K. ; Starr, John M. ; Stirrups, Kathleen E. ; Stitziel, Nathan ; Strauch, Konstantin ; Stringham, Heather M. ; Surendran, Praveen ; Tada, Hayato ; Tall, Alan R. ; Tang, Hua ; Tardif, Jean Claude ; Taylor, Kent D. ; Trompet, Stella ; Tsao, Philip S. ; Tuomilehto, Jaakko ; Tybjaerg-Hansen, Anne ; Zuydam, Natalie R.Van ; Varbo, Anette ; Varga, Tibor V. ; Virtamo, Jarmo ; Waldenberger, Melanie ; Wang, Nan ; Wareham, Nick J. ; Warren, Helen R. ; Weeke, Peter E. ; Weinstock, Joshua ; Wessel, Jennifer ; Wilson, James G. ; Wilson, Peter W.F. ; Xu, Ming ; Yaghootkar, Hanieh ; Young, Robin ; Zeggini, Eleftheria ; Zhang, He ; Zheng, Neil S. ; Zhang, Weihua ; Zhang, Yan ; Zhou, Wei ; Zhou, Yanhua ; Zoledziewska, Magdalena ; Howson, Joanna M.M. ; Danesh, John ; McCarthy, Mark I. ; Cowan, Chad A. ; Abecasis, Goncalo ; Deloukas, Panos ; Musunuru, Kiran ; Willer, Cristen J. ; Kathiresan, Sekar ; V Varga, Tibor. / Exome-wide association study of plasma lipids in >300,000 individuals. I: Nature Genetics. 2017 ; Bind 49, Nr. 12. s. 1758-1766.
Bibtex
@article{a29cce0ea320433291455842de53c720,
title = "Exome-wide association study of plasma lipids in >300,000 individuals",
abstract = "We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TGrich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.",
author = "Liu, {Dajiang J.} and Peloso, {Gina M.} and Haojie Yu and Butterworth, {Adam S.} and Xiao Wang and Anubha Mahajan and Danish Saleheen and Connor Emdin and Dewan Alam and Alves, {Alexessander Couto} and Philippe Amouyel and Angelantonio, {Emanuele DI} and Dominique Arveiler and Assimes, {Themistocles L.} and Auer, {Paul L.} and Usman Baber and Ballantyne, {Christie M.} and Bang, {Lia E.} and Marianne Benn and Bis, {Joshua C.} and Michael Boehnke and Eric Boerwinkle and Jette Bork-Jensen and Bottinger, {Erwin P.} and Ivan Brandslund and Morris Brown and Fabio Busonero and Caulfield, {Mark J.} and Chambers, {John C.} and Chasman, {Daniel I.} and Chen, {Y. Eugene} and Chen, {Yii Der Ida} and Rajiv Chowdhury and Cramer Christensen and Chu, {Audrey Y.} and Connell, {John M.} and Francesco Cucca and Cupples, {L. Adrienne} and Damrauer, {Scott M.} and Gail Davies and Deary, {Ian J.} and George Dedoussis and Denny, {Joshua C.} and Anna Dominiczak and Dub{\'e}, {Marie Pierre} and Tapani Ebeling and Gudny Eiriksdottir and To{\~n}u Esko and Farmaki, {Aliki Eleni} and Feitosa, {Mary F.} and Marco Ferrario and Jean Ferrieres and Ian Ford and Myriam Fornage and Franks, {Paul W.} and Frayling, {Timothy M.} and Ruth Frikke-Schmidt and Fritsche, {Lars G.} and Philippe Frossard and Valentin Fuster and Ganesh, {Santhi K.} and Wei Gao and Garcia, {Melissa E.} and Christian Gieger and Franco Giulianini and Goodarzi, {Mark O.} and Harald Grallert and Niels Grarup and Leif Groop and Grove, {Megan L.} and Vilmundur Gudnason and Torben Hansen and Harris, {Tamara B.} and Caroline Hayward and Hirschhorn, {Joel N.} and Holmen, {Oddgeir L.} and Jennifer Huffman and Yong Huo and Kristian Hveem and Sehrish Jabeen and Jackson, {Anne U.} and Johanna Jakobsdottir and Jarvelin, {Marjo Riitta} and Jensen, {Gorm B.} and J{\o}rgensen, {Marit E.} and Jukema, {J. Wouter} and Justesen, {Johanne M.} and Kamstrup, {Pia R.} and Stavroula Kanoni and Fredrik Karpe and Frank Kee and Khera, {Amit V.} and Derek Klarin and Koistinen, {Heikki A.} and Kooner, {Jaspal S.} and Charles Kooperberg and Kari Kuulasmaa and Johanna Kuusisto and Markku Laakso and Timo Lakka and Claudia Langenberg and Anne Langsted and Launer, {Lenore J.} and Torsten Lauritzen and MLiewald, {David C.} and Lin, {Li An} and Allan Linneberg and Loos, {Ruth J.F.} and Yingchang Lu and Xiangfeng Lu and Reedik M{\"a}gi and Anders Malarstig and Ani Manichaikul and Manning, {Alisa K.} and Pekka M{\"a}ntyselk{\"a} and Eirini Marouli and Masca, {Nicholas G.D.} and Andrea Maschio and Meigs, {James B.} and Olle Melander and Andres Metspalu and Morris, {Andrew P.} and Morrison, {Alanna C.} and Antonella Mulas and Martina M{\"u}ller-Nurasyid and Munroe, {Patricia B.} and Neville, {Matt J.} and Nielsen, {Sune F.} and Nielsen, {Jonas B.} and Nordestgaard, {B{\o}rge G.} and Ordovas, {Jose M.} and Roxana Mehran and O'Donnell, {Christoper J.} and Marju Orho-Melander and Molony, {Cliona M.} and Pieter Muntendam and Sandosh Padmanabhan and Palmer, {Colin N.A.} and Dorota Pasko and Patel, {Aniruddh P.} and Oluf Pedersen and Markus Perola and Annette Peters and Charlotta Pisinger and Giorgio Pistis and Ozren Polasek and Neil Poulter and Psaty, {Bruce M.} and Rader, {Daniel J.} and Asif Rasheed and Rainer Rauramaa and Reilly, {Dermot F.} and Reiner, {Alex P.} and Frida Renstr{\"o}m and Rich, {Stephen S.} and Ridker, {Paul M.} and Rioux, {John D.} and Robertson, {Neil R.} and Roden, {Dan M.} and Rotter, {Jerome I.} and Igor Rudan and Veikko Salomaa and Samani, {Nilesh J.} and Serena Sanna and Naveed Sattar and Schmidt, {Ellen M.} and Scott, {Robert A.} and Peter Sever and Sevilla, {Raquel S.} and Shaffer, {Christian M.} and Xueling Sim and Suthesh Sivapalaratnam and Small, {Kerrin S.} and Smith, {Albert V.} and Smith, {Blair H.} and Sangeetha Somayajula and Lorraine Southam and Spector, {Timothy D.} and Speliotes, {Elizabeth K.} and Starr, {John M.} and Stirrups, {Kathleen E.} and Nathan Stitziel and Konstantin Strauch and Stringham, {Heather M.} and Praveen Surendran and Hayato Tada and Tall, {Alan R.} and Hua Tang and Tardif, {Jean Claude} and Taylor, {Kent D.} and Stella Trompet and Tsao, {Philip S.} and Jaakko Tuomilehto and Anne Tybjaerg-Hansen and Zuydam, {Natalie R.Van} and Anette Varbo and Varga, {Tibor V.} and Jarmo Virtamo and Melanie Waldenberger and Nan Wang and Wareham, {Nick J.} and Warren, {Helen R.} and Weeke, {Peter E.} and Joshua Weinstock and Jennifer Wessel and Wilson, {James G.} and Wilson, {Peter W.F.} and Ming Xu and Hanieh Yaghootkar and Robin Young and Eleftheria Zeggini and He Zhang and Zheng, {Neil S.} and Weihua Zhang and Yan Zhang and Wei Zhou and Yanhua Zhou and Magdalena Zoledziewska and Howson, {Joanna M.M.} and John Danesh and McCarthy, {Mark I.} and Cowan, {Chad A.} and Goncalo Abecasis and Panos Deloukas and Kiran Musunuru and Willer, {Cristen J.} and Sekar Kathiresan and {V Varga}, Tibor",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/ng.3977",
language = "English",
volume = "49",
pages = "1758--1766",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "12",
}
RIS
TY - JOUR
T1 - Exome-wide association study of plasma lipids in >300,000 individuals
AU - Liu, Dajiang J.
AU - Peloso, Gina M.
AU - Yu, Haojie
AU - Butterworth, Adam S.
AU - Wang, Xiao
AU - Mahajan, Anubha
AU - Saleheen, Danish
AU - Emdin, Connor
AU - Alam, Dewan
AU - Alves, Alexessander Couto
AU - Amouyel, Philippe
AU - Angelantonio, Emanuele DI
AU - Arveiler, Dominique
AU - Assimes, Themistocles L.
AU - Auer, Paul L.
AU - Baber, Usman
AU - Ballantyne, Christie M.
AU - Bang, Lia E.
AU - Benn, Marianne
AU - Bis, Joshua C.
AU - Boehnke, Michael
AU - Boerwinkle, Eric
AU - Bork-Jensen, Jette
AU - Bottinger, Erwin P.
AU - Brandslund, Ivan
AU - Brown, Morris
AU - Busonero, Fabio
AU - Caulfield, Mark J.
AU - Chambers, John C.
AU - Chasman, Daniel I.
AU - Chen, Y. Eugene
AU - Chen, Yii Der Ida
AU - Chowdhury, Rajiv
AU - Christensen, Cramer
AU - Chu, Audrey Y.
AU - Connell, John M.
AU - Cucca, Francesco
AU - Cupples, L. Adrienne
AU - Damrauer, Scott M.
AU - Davies, Gail
AU - Deary, Ian J.
AU - Dedoussis, George
AU - Denny, Joshua C.
AU - Dominiczak, Anna
AU - Dubé, Marie Pierre
AU - Ebeling, Tapani
AU - Eiriksdottir, Gudny
AU - Esko, Toñu
AU - Farmaki, Aliki Eleni
AU - Feitosa, Mary F.
AU - Ferrario, Marco
AU - Ferrieres, Jean
AU - Ford, Ian
AU - Fornage, Myriam
AU - Franks, Paul W.
AU - Frayling, Timothy M.
AU - Frikke-Schmidt, Ruth
AU - Fritsche, Lars G.
AU - Frossard, Philippe
AU - Fuster, Valentin
AU - Ganesh, Santhi K.
AU - Gao, Wei
AU - Garcia, Melissa E.
AU - Gieger, Christian
AU - Giulianini, Franco
AU - Goodarzi, Mark O.
AU - Grallert, Harald
AU - Grarup, Niels
AU - Groop, Leif
AU - Grove, Megan L.
AU - Gudnason, Vilmundur
AU - Hansen, Torben
AU - Harris, Tamara B.
AU - Hayward, Caroline
AU - Hirschhorn, Joel N.
AU - Holmen, Oddgeir L.
AU - Huffman, Jennifer
AU - Huo, Yong
AU - Hveem, Kristian
AU - Jabeen, Sehrish
AU - Jackson, Anne U.
AU - Jakobsdottir, Johanna
AU - Jarvelin, Marjo Riitta
AU - Jensen, Gorm B.
AU - Jørgensen, Marit E.
AU - Jukema, J. Wouter
AU - Justesen, Johanne M.
AU - Kamstrup, Pia R.
AU - Kanoni, Stavroula
AU - Karpe, Fredrik
AU - Kee, Frank
AU - Khera, Amit V.
AU - Klarin, Derek
AU - Koistinen, Heikki A.
AU - Kooner, Jaspal S.
AU - Kooperberg, Charles
AU - Kuulasmaa, Kari
AU - Kuusisto, Johanna
AU - Laakso, Markku
AU - Lakka, Timo
AU - Langenberg, Claudia
AU - Langsted, Anne
AU - Launer, Lenore J.
AU - Lauritzen, Torsten
AU - MLiewald, David C.
AU - Lin, Li An
AU - Linneberg, Allan
AU - Loos, Ruth J.F.
AU - Lu, Yingchang
AU - Lu, Xiangfeng
AU - Mägi, Reedik
AU - Malarstig, Anders
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AU - Kathiresan, Sekar
AU - V Varga, Tibor
PY - 2017/12/1
Y1 - 2017/12/1
N2 - We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TGrich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
AB - We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TGrich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
U2 - 10.1038/ng.3977
DO - 10.1038/ng.3977
M3 - Letter
C2 - 29083408
AN - SCOPUS:85035766416
VL - 49
SP - 1758
EP - 1766
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 12
ER -
