Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

Seyedeh M. Zekavat, Sanni Ruotsalainen, Robert E. Handsaker, Maris Alver, Jonathan Bloom, Timothy Poterba, Cotton Seed, Jason Ernst, Mark Chaffin, Jesse Engreitz, Gina M. Peloso, Ani Manichaikul, Chaojie Yang, Kathleen A. Ryan, Mao Fu, W. Craig Johnson, Michael Tsai, Matthew Budoff, Vasan S. Ramachandran, L. Adrienne CupplesJerome I. Rotter, Stephen S. Rich, Wendy Post, Braxton D. Mitchell, Adolfo Correa, Andres Metspalu, James G. Wilson, Veikko Salomaa, Manolis Kellis, Mark J. Daly, Benjamin M. Neale, Steven McCarroll, Ida Surakka, Tonu Esko, Andrea Ganna, Samuli Ripatti, Sekar Kathiresan, Pradeep Natarajan, Namiko Abe, Goncalo Abecasis, Christine Albert, Nicholette Palmer Allred, Laura Almasy, Alvaro Alonso, Seth Ament, Peter Anderson, Pramod Anugu, Deborah Applebaum-Bowden, Dan Arking, Donna K. Arnett, Allison Ashley-Koch, Stella Aslibekyan, Tim Assimes, Paul Auer, Dimitrios Avramopoulos, John Barnard, Kathleen Barnes, R. Graham Barr, Emily Barron-Casella, Terri Beaty, Diane Becker, Lewis Becker, Rebecca Beer, Ferdouse Begum, Amber Beitelshees, Emelia Benjamin, Marcos Bezerra, Larry Bielak, Joshua Bis, Thomas Blackwell, John Blangero, Eric Boerwinkle, Ingrid Borecki, Russell Bowler, Jennifer Brody, Ulrich Broeckel, Jai Broome, Karen Bunting, Esteban Burchard, Jonathan Cardwell, Cara Carty, Richard Casaburi, James Casella, Christy Chang, Daniel Chasman, Sameer Chavan, Bo Juen Chen, Wei Min Chen, Yii Der Ida Chen, Michael Cho, Seung Hoan Choi, Lee Ming Chuang, Mina Chung, Elaine Cornell, Carolyn Crandall, James Crapo, Joanne Curran, Jeffrey Curtis, Brian Custer, Coleen Damcott, Dawood Darbar, Sayantan Das, Sean David, Colleen Davis, Michelle Daya, Mariza De Andrade, Michael Debaun, Ranjan Deka, Dawn Demeo, Scott Devine, Ron Do, Qing Duan, Ravi Duggirala, Peter Durda, Susan Dutcher, Charles Eaton, Lynette Ekunwe, Patrick Ellinor, Leslie Emery, Charles Farber, Leanna Farnam, Tasha Fingerlin, Matthew Flickinger, Myriam Fornage, Nora Franceschini, Stephanie M. Fullerton, Lucinda Fulton, Stacey Gabriel, Weiniu Gan, Yan Gao, Margery Gass, Bruce Gelb, Xiaoqi Geng, Soren Germer, Chris Gignoux, Mark Gladwin, David Glahn, Stephanie Gogarten, Da Wei Gong, Harald Goring, C. Charles Gu, Yue Guan, Xiuqing Guo, Jeff Haessler, Michael Hall, Daniel Harris, Nicola Hawley, Jiang He, Ben Heavner, Susan Heckbert, Ryan Hernandez, David Herrington, Craig Hersh, Bertha Hidalgo, James Hixson, John Hokanson, Elliott Hong, Karin Hoth, Chao Hsiung, Haley Huston, Chii Min Hwu, Marguerite Ryan Irvin, Rebecca Jackson, Deepti Jain, Cashell Jaquish, Min A. Jhun, Jill Johnsen, Andrew Johnson, Rich Johnston, Kimberly Jones, Hyun Min Kang, Robert C. Kaplan, Sharon Kardia, Laura Kaufman, Shannon Kelly, Eimear Kenny, Michael Kessler, Alyna Khan, Greg Kinney, Barbara Konkle, Charles Kooperberg, Holly Kramer, Stephanie Krauter, Christoph Lange, Ethan Lange, Leslie Lange, Cathy Laurie, Cecelia Laurie, Meryl Leboff, Seunggeun Shawn Lee, Wen Jane Lee, Jonathon Lefaive, David Levine, Dan Levy, Joshua Lewis, Yun Li, Honghuang Lin, Keng Han Lin, Simin Liu, Yongmei Liu, Ruth Loos, Steven Lubitz, Kathryn Lunetta, James Luo, Michael Mahaney, Barry Make, Jo Ann Manson, Lauren Margolin, Lisa Martin, Susan Mathai, Rasika Mathias, Patrick McArdle, Merry Lynn McDonald, Sean McFarland, Stephen McGarvey, Hao Mei, Deborah A. Meyers, Julie Mikulla, Nancy Min, Mollie Minear, Ryan L. Minster, May E. Montasser, Solomon Musani, Stanford Mwasongwe, Josyf C. Mychaleckyj, Girish Nadkarni, Rakhi Naik, Sergei Nekhai, Deborah Nickerson, Kari North, Jeff O'connell, Tim O'connor, Heather Ochs-Balcom, James Pankow, George Papanicolaou, Margaret Parker, Afshin Parsa, Sara Penchev, Juan Manuel Peralta, Marco Perez, James Perry, Ulrike Peters, Patricia Peyser, Larry Phillips, Sam Phillips, Toni Pollin, Julia Powers Becker, Meher Preethi Boorgula, Michael Preuss, Dmitry Prokopenko, Bruce Psaty, Pankaj Qasba, Dandi Qiao, Zhaohui Qin, Nicholas Rafaels, Laura Raffield, D. C. Rao, Laura Rasmussen-Torvik, Aakrosh Ratan, Susan Redline, Robert Reed, Elizabeth Regan, Alex Reiner, Ken Rice, Dan Roden, Carolina Roselli, Ingo Ruczinski, Pamela Russell, Sarah Ruuska, Phuwanat Sakornsakolpat, Shabnam Salimi, Steven Salzberg, Kevin Sandow, Vijay Sankaran, Christopher Scheller, Ellen Schmidt, Karen Schwander, David Schwartz, Frank Sciurba, Christine Seidman, Vivien Sheehan, Amol Shetty, Aniket Shetty, Wayne Hui Heng Sheu, M. Benjamin Shoemaker, Brian Silver, Edwin Silverman, Jennifer Smith, Josh Smith, Nicholas Smith, Tanja Smith, Sylvia Smoller, Beverly Snively, Tamar Sofer, Nona Sotoodehnia, Adrienne Stilp, Elizabeth Streeten, Yun Ju Sung, Jody Sylvia, Adam Szpiro, Carole Sztalryd, Daniel Taliun, Hua Tang, Margaret Taub, Kent Taylor, Simeon Taylor, Marilyn Telen, Timothy A. Thornton, Lesley Tinker, David Tirschwell, Hemant Tiwari, Russell Tracy, Dhananjay Vaidya, Peter Vandehaar, Scott Vrieze, Tarik Walker, Robert Wallace, Avram Walts, Emily Wan, Fei Fei Wang, Karol Watson, Daniel E. Weeks, Bruce Weir, Scott Weiss, Lu Chen Weng, Cristen Willer, Kayleen Williams, L. Keoki Williams, Carla Wilson, Quenna Wong, Huichun Xu, Lisa Yanek, Ivana Yang, Rongze Yang, Norann Zaghloul, Yingze Zhang, Snow Xueyan Zhao, Wei Zhao, Xiuwen Zheng, Degui Zhi, Xiang Zhou, Michael Zody, Sebastian Zoellner

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.

Original languageEnglish (US)
Article number2606
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

lipoproteins
Lipoprotein(a)
genome
Cardiovascular Diseases
Genes
cholesterol
Genome
Kringles
Apoprotein(a)
Plasmas
determinants
LDL Lipoproteins
African Americans
LDL Cholesterol
arteriosclerosis
Atherosclerosis
sequencing
Nucleotides
Cholesterol
Genotype

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Zekavat, S. M., Ruotsalainen, S., Handsaker, R. E., Alver, M., Bloom, J., Poterba, T., ... Zoellner, S. (2018). Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries. Nature Communications, 9(1), [2606]. https://doi.org/10.1038/s41467-018-04668-w

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries. / Zekavat, Seyedeh M.; Ruotsalainen, Sanni; Handsaker, Robert E.; Alver, Maris; Bloom, Jonathan; Poterba, Timothy; Seed, Cotton; Ernst, Jason; Chaffin, Mark; Engreitz, Jesse; Peloso, Gina M.; Manichaikul, Ani; Yang, Chaojie; Ryan, Kathleen A.; Fu, Mao; Johnson, W. Craig; Tsai, Michael; Budoff, Matthew; Ramachandran, Vasan S.; Cupples, L. Adrienne; Rotter, Jerome I.; Rich, Stephen S.; Post, Wendy; Mitchell, Braxton D.; Correa, Adolfo; Metspalu, Andres; Wilson, James G.; Salomaa, Veikko; Kellis, Manolis; Daly, Mark J.; Neale, Benjamin M.; McCarroll, Steven; Surakka, Ida; Esko, Tonu; Ganna, Andrea; Ripatti, Samuli; Kathiresan, Sekar; Natarajan, Pradeep; Abe, Namiko; Abecasis, Goncalo; Albert, Christine; Allred, Nicholette Palmer; Almasy, Laura; Alonso, Alvaro; Ament, Seth; Anderson, Peter; Anugu, Pramod; Applebaum-Bowden, Deborah; Arking, Dan; Arnett, Donna K.; Ashley-Koch, Allison; Aslibekyan, Stella; Assimes, Tim; Auer, Paul; Avramopoulos, Dimitrios; Barnard, John; Barnes, Kathleen; Barr, R. Graham; Barron-Casella, Emily; Beaty, Terri; Becker, Diane; Becker, Lewis; Beer, Rebecca; Begum, Ferdouse; Beitelshees, Amber; Benjamin, Emelia; Bezerra, Marcos; Bielak, Larry; Bis, Joshua; Blackwell, Thomas; Blangero, John; Boerwinkle, Eric; Borecki, Ingrid; Bowler, Russell; Brody, Jennifer; Broeckel, Ulrich; Broome, Jai; Bunting, Karen; Burchard, Esteban; Cardwell, Jonathan; Carty, Cara; Casaburi, Richard; Casella, James; Chang, Christy; Chasman, Daniel; Chavan, Sameer; Chen, Bo Juen; Chen, Wei Min; Chen, Yii Der Ida; Cho, Michael; Choi, Seung Hoan; Chuang, Lee Ming; Chung, Mina; Cornell, Elaine; Crandall, Carolyn; Crapo, James; Curran, Joanne; Curtis, Jeffrey; Custer, Brian; Damcott, Coleen; Darbar, Dawood; Das, Sayantan; David, Sean; Davis, Colleen; Daya, Michelle; Andrade, Mariza De; Debaun, Michael; Deka, Ranjan; Demeo, Dawn; Devine, Scott; Do, Ron; Duan, Qing; Duggirala, Ravi; Durda, Peter; Dutcher, Susan; Eaton, Charles; Ekunwe, Lynette; Ellinor, Patrick; Emery, Leslie; Farber, Charles; Farnam, Leanna; Fingerlin, Tasha; Flickinger, Matthew; Fornage, Myriam; Franceschini, Nora; Fullerton, Stephanie M.; Fulton, Lucinda; Gabriel, Stacey; Gan, Weiniu; Gao, Yan; Gass, Margery; Gelb, Bruce; Geng, Xiaoqi; Germer, Soren; Gignoux, Chris; Gladwin, Mark; Glahn, David; Gogarten, Stephanie; Gong, Da Wei; Goring, Harald; Gu, C. Charles; Guan, Yue; Guo, Xiuqing; Haessler, Jeff; Hall, Michael; Harris, Daniel; Hawley, Nicola; He, Jiang; Heavner, Ben; Heckbert, Susan; Hernandez, Ryan; Herrington, David; Hersh, Craig; Hidalgo, Bertha; Hixson, James; Hokanson, John; Hong, Elliott; Hoth, Karin; Hsiung, Chao; Huston, Haley; Hwu, Chii Min; Irvin, Marguerite Ryan; Jackson, Rebecca; Jain, Deepti; Jaquish, Cashell; Jhun, Min A.; Johnsen, Jill; Johnson, Andrew; Johnston, Rich; Jones, Kimberly; Kang, Hyun Min; Kaplan, Robert C.; Kardia, Sharon; Kaufman, Laura; Kelly, Shannon; Kenny, Eimear; Kessler, Michael; Khan, Alyna; Kinney, Greg; Konkle, Barbara; Kooperberg, Charles; Kramer, Holly; Krauter, Stephanie; Lange, Christoph; Lange, Ethan; Lange, Leslie; Laurie, Cathy; Laurie, Cecelia; Leboff, Meryl; Lee, Seunggeun Shawn; Lee, Wen Jane; Lefaive, Jonathon; Levine, David; Levy, Dan; Lewis, Joshua; Li, Yun; Lin, Honghuang; Lin, Keng Han; Liu, Simin; Liu, Yongmei; Loos, Ruth; Lubitz, Steven; Lunetta, Kathryn; Luo, James; Mahaney, Michael; Make, Barry; Manson, Jo Ann; Margolin, Lauren; Martin, Lisa; Mathai, Susan; Mathias, Rasika; McArdle, Patrick; McDonald, Merry Lynn; McFarland, Sean; McGarvey, Stephen; Mei, Hao; Meyers, Deborah A.; Mikulla, Julie; Min, Nancy; Minear, Mollie; Minster, Ryan L.; Montasser, May E.; Musani, Solomon; Mwasongwe, Stanford; Mychaleckyj, Josyf C.; Nadkarni, Girish; Naik, Rakhi; Nekhai, Sergei; Nickerson, Deborah; North, Kari; O'connell, Jeff; O'connor, Tim; Ochs-Balcom, Heather; Pankow, James; Papanicolaou, George; Parker, Margaret; Parsa, Afshin; Penchev, Sara; Peralta, Juan Manuel; Perez, Marco; Perry, James; Peters, Ulrike; Peyser, Patricia; Phillips, Larry; Phillips, Sam; Pollin, Toni; Becker, Julia Powers; Boorgula, Meher Preethi; Preuss, Michael; Prokopenko, Dmitry; Psaty, Bruce; Qasba, Pankaj; Qiao, Dandi; Qin, Zhaohui; Rafaels, Nicholas; Raffield, Laura; Rao, D. C.; Rasmussen-Torvik, Laura; Ratan, Aakrosh; Redline, Susan; Reed, Robert; Regan, Elizabeth; Reiner, Alex; Rice, Ken; Roden, Dan; Roselli, Carolina; Ruczinski, Ingo; Russell, Pamela; Ruuska, Sarah; Sakornsakolpat, Phuwanat; Salimi, Shabnam; Salzberg, Steven; Sandow, Kevin; Sankaran, Vijay; Scheller, Christopher; Schmidt, Ellen; Schwander, Karen; Schwartz, David; Sciurba, Frank; Seidman, Christine; Sheehan, Vivien; Shetty, Amol; Shetty, Aniket; Sheu, Wayne Hui Heng; Shoemaker, M. Benjamin; Silver, Brian; Silverman, Edwin; Smith, Jennifer; Smith, Josh; Smith, Nicholas; Smith, Tanja; Smoller, Sylvia; Snively, Beverly; Sofer, Tamar; Sotoodehnia, Nona; Stilp, Adrienne; Streeten, Elizabeth; Sung, Yun Ju; Sylvia, Jody; Szpiro, Adam; Sztalryd, Carole; Taliun, Daniel; Tang, Hua; Taub, Margaret; Taylor, Kent; Taylor, Simeon; Telen, Marilyn; Thornton, Timothy A.; Tinker, Lesley; Tirschwell, David; Tiwari, Hemant; Tracy, Russell; Vaidya, Dhananjay; Vandehaar, Peter; Vrieze, Scott; Walker, Tarik; Wallace, Robert; Walts, Avram; Wan, Emily; Wang, Fei Fei; Watson, Karol; Weeks, Daniel E.; Weir, Bruce; Weiss, Scott; Weng, Lu Chen; Willer, Cristen; Williams, Kayleen; Williams, L. Keoki; Wilson, Carla; Wong, Quenna; Xu, Huichun; Yanek, Lisa; Yang, Ivana; Yang, Rongze; Zaghloul, Norann; Zhang, Yingze; Zhao, Snow Xueyan; Zhao, Wei; Zheng, Xiuwen; Zhi, Degui; Zhou, Xiang; Zody, Michael; Zoellner, Sebastian.

In: Nature Communications, Vol. 9, No. 1, 2606, 01.12.2018.

Research output: Contribution to journalArticle

Zekavat, SM, Ruotsalainen, S, Handsaker, RE, Alver, M, Bloom, J, Poterba, T, Seed, C, Ernst, J, Chaffin, M, Engreitz, J, Peloso, GM, Manichaikul, A, Yang, C, Ryan, KA, Fu, M, Johnson, WC, Tsai, M, Budoff, M, Ramachandran, VS, Cupples, LA, Rotter, JI, Rich, SS, Post, W, Mitchell, BD, Correa, A, Metspalu, A, Wilson, JG, Salomaa, V, Kellis, M, Daly, MJ, Neale, BM, McCarroll, S, Surakka, I, Esko, T, Ganna, A, Ripatti, S, Kathiresan, S, Natarajan, P, Abe, N, Abecasis, G, Albert, C, Allred, NP, Almasy, L, Alonso, A, Ament, S, Anderson, P, Anugu, P, Applebaum-Bowden, D, Arking, D, Arnett, DK, Ashley-Koch, A, Aslibekyan, S, Assimes, T, Auer, P, Avramopoulos, D, Barnard, J, Barnes, K, Barr, RG, Barron-Casella, E, Beaty, T, Becker, D, Becker, L, Beer, R, Begum, F, Beitelshees, A, Benjamin, E, Bezerra, M, Bielak, L, Bis, J, Blackwell, T, Blangero, J, Boerwinkle, E, Borecki, I, Bowler, R, Brody, J, Broeckel, U, Broome, J, Bunting, K, Burchard, E, Cardwell, J, Carty, C, Casaburi, R, Casella, J, Chang, C, Chasman, D, Chavan, S, Chen, BJ, Chen, WM, Chen, YDI, Cho, M, Choi, SH, Chuang, LM, Chung, M, Cornell, E, Crandall, C, Crapo, J, Curran, J, Curtis, J, Custer, B, Damcott, C, Darbar, D, Das, S, David, S, Davis, C, Daya, M, Andrade, MD, Debaun, M, Deka, R, Demeo, D, Devine, S, Do, R, Duan, Q, Duggirala, R, Durda, P, Dutcher, S, Eaton, C, Ekunwe, L, Ellinor, P, Emery, L, Farber, C, Farnam, L, Fingerlin, T, Flickinger, M, Fornage, M, Franceschini, N, Fullerton, SM, Fulton, L, Gabriel, S, Gan, W, Gao, Y, Gass, M, Gelb, B, Geng, X, Germer, S, Gignoux, C, Gladwin, M, Glahn, D, Gogarten, S, Gong, DW, Goring, H, Gu, CC, Guan, Y, Guo, X, Haessler, J, Hall, M, Harris, D, Hawley, N, He, J, Heavner, B, Heckbert, S, Hernandez, R, Herrington, D, Hersh, C, Hidalgo, B, Hixson, J, Hokanson, J, Hong, E, Hoth, K, Hsiung, C, Huston, H, Hwu, CM, Irvin, MR, Jackson, R, Jain, D, Jaquish, C, Jhun, MA, Johnsen, J, Johnson, A, Johnston, R, Jones, K, Kang, HM, Kaplan, RC, Kardia, S, Kaufman, L, Kelly, S, Kenny, E, Kessler, M, Khan, A, Kinney, G, Konkle, B, Kooperberg, C, Kramer, H, Krauter, S, Lange, C, Lange, E, Lange, L, Laurie, C, Laurie, C, Leboff, M, Lee, SS, Lee, WJ, Lefaive, J, Levine, D, Levy, D, Lewis, J, Li, Y, Lin, H, Lin, KH, Liu, S, Liu, Y, Loos, R, Lubitz, S, Lunetta, K, Luo, J, Mahaney, M, Make, B, Manson, JA, Margolin, L, Martin, L, Mathai, S, Mathias, R, McArdle, P, McDonald, ML, McFarland, S, McGarvey, S, Mei, H, Meyers, DA, Mikulla, J, Min, N, Minear, M, Minster, RL, Montasser, ME, Musani, S, Mwasongwe, S, Mychaleckyj, JC, Nadkarni, G, Naik, R, Nekhai, S, Nickerson, D, North, K, O'connell, J, O'connor, T, Ochs-Balcom, H, Pankow, J, Papanicolaou, G, Parker, M, Parsa, A, Penchev, S, Peralta, JM, Perez, M, Perry, J, Peters, U, Peyser, P, Phillips, L, Phillips, S, Pollin, T, Becker, JP, Boorgula, MP, Preuss, M, Prokopenko, D, Psaty, B, Qasba, P, Qiao, D, Qin, Z, Rafaels, N, Raffield, L, Rao, DC, Rasmussen-Torvik, L, Ratan, A, Redline, S, Reed, R, Regan, E, Reiner, A, Rice, K, Roden, D, Roselli, C, Ruczinski, I, Russell, P, Ruuska, S, Sakornsakolpat, P, Salimi, S, Salzberg, S, Sandow, K, Sankaran, V, Scheller, C, Schmidt, E, Schwander, K, Schwartz, D, Sciurba, F, Seidman, C, Sheehan, V, Shetty, A, Shetty, A, Sheu, WHH, Shoemaker, MB, Silver, B, Silverman, E, Smith, J, Smith, J, Smith, N, Smith, T, Smoller, S, Snively, B, Sofer, T, Sotoodehnia, N, Stilp, A, Streeten, E, Sung, YJ, Sylvia, J, Szpiro, A, Sztalryd, C, Taliun, D, Tang, H, Taub, M, Taylor, K, Taylor, S, Telen, M, Thornton, TA, Tinker, L, Tirschwell, D, Tiwari, H, Tracy, R, Vaidya, D, Vandehaar, P, Vrieze, S, Walker, T, Wallace, R, Walts, A, Wan, E, Wang, FF, Watson, K, Weeks, DE, Weir, B, Weiss, S, Weng, LC, Willer, C, Williams, K, Williams, LK, Wilson, C, Wong, Q, Xu, H, Yanek, L, Yang, I, Yang, R, Zaghloul, N, Zhang, Y, Zhao, SX, Zhao, W, Zheng, X, Zhi, D, Zhou, X, Zody, M & Zoellner, S 2018, 'Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries', Nature Communications, vol. 9, no. 1, 2606. https://doi.org/10.1038/s41467-018-04668-w
Zekavat, Seyedeh M. ; Ruotsalainen, Sanni ; Handsaker, Robert E. ; Alver, Maris ; Bloom, Jonathan ; Poterba, Timothy ; Seed, Cotton ; Ernst, Jason ; Chaffin, Mark ; Engreitz, Jesse ; Peloso, Gina M. ; Manichaikul, Ani ; Yang, Chaojie ; Ryan, Kathleen A. ; Fu, Mao ; Johnson, W. Craig ; Tsai, Michael ; Budoff, Matthew ; Ramachandran, Vasan S. ; Cupples, L. Adrienne ; Rotter, Jerome I. ; Rich, Stephen S. ; Post, Wendy ; Mitchell, Braxton D. ; Correa, Adolfo ; Metspalu, Andres ; Wilson, James G. ; Salomaa, Veikko ; Kellis, Manolis ; Daly, Mark J. ; Neale, Benjamin M. ; McCarroll, Steven ; Surakka, Ida ; Esko, Tonu ; Ganna, Andrea ; Ripatti, Samuli ; Kathiresan, Sekar ; Natarajan, Pradeep ; Abe, Namiko ; Abecasis, Goncalo ; Albert, Christine ; Allred, Nicholette Palmer ; Almasy, Laura ; Alonso, Alvaro ; Ament, Seth ; Anderson, Peter ; Anugu, Pramod ; Applebaum-Bowden, Deborah ; Arking, Dan ; Arnett, Donna K. ; Ashley-Koch, Allison ; Aslibekyan, Stella ; Assimes, Tim ; Auer, Paul ; Avramopoulos, Dimitrios ; Barnard, John ; Barnes, Kathleen ; Barr, R. Graham ; Barron-Casella, Emily ; Beaty, Terri ; Becker, Diane ; Becker, Lewis ; Beer, Rebecca ; Begum, Ferdouse ; Beitelshees, Amber ; Benjamin, Emelia ; Bezerra, Marcos ; Bielak, Larry ; Bis, Joshua ; Blackwell, Thomas ; Blangero, John ; Boerwinkle, Eric ; Borecki, Ingrid ; Bowler, Russell ; Brody, Jennifer ; Broeckel, Ulrich ; Broome, Jai ; Bunting, Karen ; Burchard, Esteban ; Cardwell, Jonathan ; Carty, Cara ; Casaburi, Richard ; Casella, James ; Chang, Christy ; Chasman, Daniel ; Chavan, Sameer ; Chen, Bo Juen ; Chen, Wei Min ; Chen, Yii Der Ida ; Cho, Michael ; Choi, Seung Hoan ; Chuang, Lee Ming ; Chung, Mina ; Cornell, Elaine ; Crandall, Carolyn ; Crapo, James ; Curran, Joanne ; Curtis, Jeffrey ; Custer, Brian ; Damcott, Coleen ; Darbar, Dawood ; Das, Sayantan ; David, Sean ; Davis, Colleen ; Daya, Michelle ; Andrade, Mariza De ; Debaun, Michael ; Deka, Ranjan ; Demeo, Dawn ; Devine, Scott ; Do, Ron ; Duan, Qing ; Duggirala, Ravi ; Durda, Peter ; Dutcher, Susan ; Eaton, Charles ; Ekunwe, Lynette ; Ellinor, Patrick ; Emery, Leslie ; Farber, Charles ; Farnam, Leanna ; Fingerlin, Tasha ; Flickinger, Matthew ; Fornage, Myriam ; Franceschini, Nora ; Fullerton, Stephanie M. ; Fulton, Lucinda ; Gabriel, Stacey ; Gan, Weiniu ; Gao, Yan ; Gass, Margery ; Gelb, Bruce ; Geng, Xiaoqi ; Germer, Soren ; Gignoux, Chris ; Gladwin, Mark ; Glahn, David ; Gogarten, Stephanie ; Gong, Da Wei ; Goring, Harald ; Gu, C. Charles ; Guan, Yue ; Guo, Xiuqing ; Haessler, Jeff ; Hall, Michael ; Harris, Daniel ; Hawley, Nicola ; He, Jiang ; Heavner, Ben ; Heckbert, Susan ; Hernandez, Ryan ; Herrington, David ; Hersh, Craig ; Hidalgo, Bertha ; Hixson, James ; Hokanson, John ; Hong, Elliott ; Hoth, Karin ; Hsiung, Chao ; Huston, Haley ; Hwu, Chii Min ; Irvin, Marguerite Ryan ; Jackson, Rebecca ; Jain, Deepti ; Jaquish, Cashell ; Jhun, Min A. ; Johnsen, Jill ; Johnson, Andrew ; Johnston, Rich ; Jones, Kimberly ; Kang, Hyun Min ; Kaplan, Robert C. ; Kardia, Sharon ; Kaufman, Laura ; Kelly, Shannon ; Kenny, Eimear ; Kessler, Michael ; Khan, Alyna ; Kinney, Greg ; Konkle, Barbara ; Kooperberg, Charles ; Kramer, Holly ; Krauter, Stephanie ; Lange, Christoph ; Lange, Ethan ; Lange, Leslie ; Laurie, Cathy ; Laurie, Cecelia ; Leboff, Meryl ; Lee, Seunggeun Shawn ; Lee, Wen Jane ; Lefaive, Jonathon ; Levine, David ; Levy, Dan ; Lewis, Joshua ; Li, Yun ; Lin, Honghuang ; Lin, Keng Han ; Liu, Simin ; Liu, Yongmei ; Loos, Ruth ; Lubitz, Steven ; Lunetta, Kathryn ; Luo, James ; Mahaney, Michael ; Make, Barry ; Manson, Jo Ann ; Margolin, Lauren ; Martin, Lisa ; Mathai, Susan ; Mathias, Rasika ; McArdle, Patrick ; McDonald, Merry Lynn ; McFarland, Sean ; McGarvey, Stephen ; Mei, Hao ; Meyers, Deborah A. ; Mikulla, Julie ; Min, Nancy ; Minear, Mollie ; Minster, Ryan L. ; Montasser, May E. ; Musani, Solomon ; Mwasongwe, Stanford ; Mychaleckyj, Josyf C. ; Nadkarni, Girish ; Naik, Rakhi ; Nekhai, Sergei ; Nickerson, Deborah ; North, Kari ; O'connell, Jeff ; O'connor, Tim ; Ochs-Balcom, Heather ; Pankow, James ; Papanicolaou, George ; Parker, Margaret ; Parsa, Afshin ; Penchev, Sara ; Peralta, Juan Manuel ; Perez, Marco ; Perry, James ; Peters, Ulrike ; Peyser, Patricia ; Phillips, Larry ; Phillips, Sam ; Pollin, Toni ; Becker, Julia Powers ; Boorgula, Meher Preethi ; Preuss, Michael ; Prokopenko, Dmitry ; Psaty, Bruce ; Qasba, Pankaj ; Qiao, Dandi ; Qin, Zhaohui ; Rafaels, Nicholas ; Raffield, Laura ; Rao, D. C. ; Rasmussen-Torvik, Laura ; Ratan, Aakrosh ; Redline, Susan ; Reed, Robert ; Regan, Elizabeth ; Reiner, Alex ; Rice, Ken ; Roden, Dan ; Roselli, Carolina ; Ruczinski, Ingo ; Russell, Pamela ; Ruuska, Sarah ; Sakornsakolpat, Phuwanat ; Salimi, Shabnam ; Salzberg, Steven ; Sandow, Kevin ; Sankaran, Vijay ; Scheller, Christopher ; Schmidt, Ellen ; Schwander, Karen ; Schwartz, David ; Sciurba, Frank ; Seidman, Christine ; Sheehan, Vivien ; Shetty, Amol ; Shetty, Aniket ; Sheu, Wayne Hui Heng ; Shoemaker, M. Benjamin ; Silver, Brian ; Silverman, Edwin ; Smith, Jennifer ; Smith, Josh ; Smith, Nicholas ; Smith, Tanja ; Smoller, Sylvia ; Snively, Beverly ; Sofer, Tamar ; Sotoodehnia, Nona ; Stilp, Adrienne ; Streeten, Elizabeth ; Sung, Yun Ju ; Sylvia, Jody ; Szpiro, Adam ; Sztalryd, Carole ; Taliun, Daniel ; Tang, Hua ; Taub, Margaret ; Taylor, Kent ; Taylor, Simeon ; Telen, Marilyn ; Thornton, Timothy A. ; Tinker, Lesley ; Tirschwell, David ; Tiwari, Hemant ; Tracy, Russell ; Vaidya, Dhananjay ; Vandehaar, Peter ; Vrieze, Scott ; Walker, Tarik ; Wallace, Robert ; Walts, Avram ; Wan, Emily ; Wang, Fei Fei ; Watson, Karol ; Weeks, Daniel E. ; Weir, Bruce ; Weiss, Scott ; Weng, Lu Chen ; Willer, Cristen ; Williams, Kayleen ; Williams, L. Keoki ; Wilson, Carla ; Wong, Quenna ; Xu, Huichun ; Yanek, Lisa ; Yang, Ivana ; Yang, Rongze ; Zaghloul, Norann ; Zhang, Yingze ; Zhao, Snow Xueyan ; Zhao, Wei ; Zheng, Xiuwen ; Zhi, Degui ; Zhou, Xiang ; Zody, Michael ; Zoellner, Sebastian. / Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries. In: Nature Communications. 2018 ; Vol. 9, No. 1.
@article{87921954614b4cd4bebb2b6522e00132,
title = "Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries",
abstract = "Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.",
author = "Zekavat, {Seyedeh M.} and Sanni Ruotsalainen and Handsaker, {Robert E.} and Maris Alver and Jonathan Bloom and Timothy Poterba and Cotton Seed and Jason Ernst and Mark Chaffin and Jesse Engreitz and Peloso, {Gina M.} and Ani Manichaikul and Chaojie Yang and Ryan, {Kathleen A.} and Mao Fu and Johnson, {W. Craig} and Michael Tsai and Matthew Budoff and Ramachandran, {Vasan S.} and Cupples, {L. Adrienne} and Rotter, {Jerome I.} and Rich, {Stephen S.} and Wendy Post and Mitchell, {Braxton D.} and Adolfo Correa and Andres Metspalu and Wilson, {James G.} and Veikko Salomaa and Manolis Kellis and Daly, {Mark J.} and Neale, {Benjamin M.} and Steven McCarroll and Ida Surakka and Tonu Esko and Andrea Ganna and Samuli Ripatti and Sekar Kathiresan and Pradeep Natarajan and Namiko Abe and Goncalo Abecasis and Christine Albert and Allred, {Nicholette Palmer} and Laura Almasy and Alvaro Alonso and Seth Ament and Peter Anderson and Pramod Anugu and Deborah Applebaum-Bowden and Dan Arking and Arnett, {Donna K.} and Allison Ashley-Koch and Stella Aslibekyan and Tim Assimes and Paul Auer and Dimitrios Avramopoulos and John Barnard and Kathleen Barnes and Barr, {R. Graham} and Emily Barron-Casella and Terri Beaty and Diane Becker and Lewis Becker and Rebecca Beer and Ferdouse Begum and Amber Beitelshees and Emelia Benjamin and Marcos Bezerra and Larry Bielak and Joshua Bis and Thomas Blackwell and John Blangero and Eric Boerwinkle and Ingrid Borecki and Russell Bowler and Jennifer Brody and Ulrich Broeckel and Jai Broome and Karen Bunting and Esteban Burchard and Jonathan Cardwell and Cara Carty and Richard Casaburi and James Casella and Christy Chang and Daniel Chasman and Sameer Chavan and Chen, {Bo Juen} and Chen, {Wei Min} and Chen, {Yii Der Ida} and Michael Cho and Choi, {Seung Hoan} and Chuang, {Lee Ming} and Mina Chung and Elaine Cornell and Carolyn Crandall and James Crapo and Joanne Curran and Jeffrey Curtis and Brian Custer and Coleen Damcott and Dawood Darbar and Sayantan Das and Sean David and Colleen Davis and Michelle Daya and Andrade, {Mariza De} and Michael Debaun and Ranjan Deka and Dawn Demeo and Scott Devine and Ron Do and Qing Duan and Ravi Duggirala and Peter Durda and Susan Dutcher and Charles Eaton and Lynette Ekunwe and Patrick Ellinor and Leslie Emery and Charles Farber and Leanna Farnam and Tasha Fingerlin and Matthew Flickinger and Myriam Fornage and Nora Franceschini and Fullerton, {Stephanie M.} and Lucinda Fulton and Stacey Gabriel and Weiniu Gan and Yan Gao and Margery Gass and Bruce Gelb and Xiaoqi Geng and Soren Germer and Chris Gignoux and Mark Gladwin and David Glahn and Stephanie Gogarten and Gong, {Da Wei} and Harald Goring and Gu, {C. Charles} and Yue Guan and Xiuqing Guo and Jeff Haessler and Michael Hall and Daniel Harris and Nicola Hawley and Jiang He and Ben Heavner and Susan Heckbert and Ryan Hernandez and David Herrington and Craig Hersh and Bertha Hidalgo and James Hixson and John Hokanson and Elliott Hong and Karin Hoth and Chao Hsiung and Haley Huston and Hwu, {Chii Min} and Irvin, {Marguerite Ryan} and Rebecca Jackson and Deepti Jain and Cashell Jaquish and Jhun, {Min A.} and Jill Johnsen and Andrew Johnson and Rich Johnston and Kimberly Jones and Kang, {Hyun Min} and Kaplan, {Robert C.} and Sharon Kardia and Laura Kaufman and Shannon Kelly and Eimear Kenny and Michael Kessler and Alyna Khan and Greg Kinney and Barbara Konkle and Charles Kooperberg and Holly Kramer and Stephanie Krauter and Christoph Lange and Ethan Lange and Leslie Lange and Cathy Laurie and Cecelia Laurie and Meryl Leboff and Lee, {Seunggeun Shawn} and Lee, {Wen Jane} and Jonathon Lefaive and David Levine and Dan Levy and Joshua Lewis and Yun Li and Honghuang Lin and Lin, {Keng Han} and Simin Liu and Yongmei Liu and Ruth Loos and Steven Lubitz and Kathryn Lunetta and James Luo and Michael Mahaney and Barry Make and Manson, {Jo Ann} and Lauren Margolin and Lisa Martin and Susan Mathai and Rasika Mathias and Patrick McArdle and McDonald, {Merry Lynn} and Sean McFarland and Stephen McGarvey and Hao Mei and Meyers, {Deborah A.} and Julie Mikulla and Nancy Min and Mollie Minear and Minster, {Ryan L.} and Montasser, {May E.} and Solomon Musani and Stanford Mwasongwe and Mychaleckyj, {Josyf C.} and Girish Nadkarni and Rakhi Naik and Sergei Nekhai and Deborah Nickerson and Kari North and Jeff O'connell and Tim O'connor and Heather Ochs-Balcom and James Pankow and George Papanicolaou and Margaret Parker and Afshin Parsa and Sara Penchev and Peralta, {Juan Manuel} and Marco Perez and James Perry and Ulrike Peters and Patricia Peyser and Larry Phillips and Sam Phillips and Toni Pollin and Becker, {Julia Powers} and Boorgula, {Meher Preethi} and Michael Preuss and Dmitry Prokopenko and Bruce Psaty and Pankaj Qasba and Dandi Qiao and Zhaohui Qin and Nicholas Rafaels and Laura Raffield and Rao, {D. C.} and Laura Rasmussen-Torvik and Aakrosh Ratan and Susan Redline and Robert Reed and Elizabeth Regan and Alex Reiner and Ken Rice and Dan Roden and Carolina Roselli and Ingo Ruczinski and Pamela Russell and Sarah Ruuska and Phuwanat Sakornsakolpat and Shabnam Salimi and Steven Salzberg and Kevin Sandow and Vijay Sankaran and Christopher Scheller and Ellen Schmidt and Karen Schwander and David Schwartz and Frank Sciurba and Christine Seidman and Vivien Sheehan and Amol Shetty and Aniket Shetty and Sheu, {Wayne Hui Heng} and Shoemaker, {M. Benjamin} and Brian Silver and Edwin Silverman and Jennifer Smith and Josh Smith and Nicholas Smith and Tanja Smith and Sylvia Smoller and Beverly Snively and Tamar Sofer and Nona Sotoodehnia and Adrienne Stilp and Elizabeth Streeten and Sung, {Yun Ju} and Jody Sylvia and Adam Szpiro and Carole Sztalryd and Daniel Taliun and Hua Tang and Margaret Taub and Kent Taylor and Simeon Taylor and Marilyn Telen and Thornton, {Timothy A.} and Lesley Tinker and David Tirschwell and Hemant Tiwari and Russell Tracy and Dhananjay Vaidya and Peter Vandehaar and Scott Vrieze and Tarik Walker and Robert Wallace and Avram Walts and Emily Wan and Wang, {Fei Fei} and Karol Watson and Weeks, {Daniel E.} and Bruce Weir and Scott Weiss and Weng, {Lu Chen} and Cristen Willer and Kayleen Williams and Williams, {L. Keoki} and Carla Wilson and Quenna Wong and Huichun Xu and Lisa Yanek and Ivana Yang and Rongze Yang and Norann Zaghloul and Yingze Zhang and Zhao, {Snow Xueyan} and Wei Zhao and Xiuwen Zheng and Degui Zhi and Xiang Zhou and Michael Zody and Sebastian Zoellner",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41467-018-04668-w",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

AU - Zekavat, Seyedeh M.

AU - Ruotsalainen, Sanni

AU - Handsaker, Robert E.

AU - Alver, Maris

AU - Bloom, Jonathan

AU - Poterba, Timothy

AU - Seed, Cotton

AU - Ernst, Jason

AU - Chaffin, Mark

AU - Engreitz, Jesse

AU - Peloso, Gina M.

AU - Manichaikul, Ani

AU - Yang, Chaojie

AU - Ryan, Kathleen A.

AU - Fu, Mao

AU - Johnson, W. Craig

AU - Tsai, Michael

AU - Budoff, Matthew

AU - Ramachandran, Vasan S.

AU - Cupples, L. Adrienne

AU - Rotter, Jerome I.

AU - Rich, Stephen S.

AU - Post, Wendy

AU - Mitchell, Braxton D.

AU - Correa, Adolfo

AU - Metspalu, Andres

AU - Wilson, James G.

AU - Salomaa, Veikko

AU - Kellis, Manolis

AU - Daly, Mark J.

AU - Neale, Benjamin M.

AU - McCarroll, Steven

AU - Surakka, Ida

AU - Esko, Tonu

AU - Ganna, Andrea

AU - Ripatti, Samuli

AU - Kathiresan, Sekar

AU - Natarajan, Pradeep

AU - Abe, Namiko

AU - Abecasis, Goncalo

AU - Albert, Christine

AU - Allred, Nicholette Palmer

AU - Almasy, Laura

AU - Alonso, Alvaro

AU - Ament, Seth

AU - Anderson, Peter

AU - Anugu, Pramod

AU - Applebaum-Bowden, Deborah

AU - Arking, Dan

AU - Arnett, Donna K.

AU - Ashley-Koch, Allison

AU - Aslibekyan, Stella

AU - Assimes, Tim

AU - Auer, Paul

AU - Avramopoulos, Dimitrios

AU - Barnard, John

AU - Barnes, Kathleen

AU - Barr, R. Graham

AU - Barron-Casella, Emily

AU - Beaty, Terri

AU - Becker, Diane

AU - Becker, Lewis

AU - Beer, Rebecca

AU - Begum, Ferdouse

AU - Beitelshees, Amber

AU - Benjamin, Emelia

AU - Bezerra, Marcos

AU - Bielak, Larry

AU - Bis, Joshua

AU - Blackwell, Thomas

AU - Blangero, John

AU - Boerwinkle, Eric

AU - Borecki, Ingrid

AU - Bowler, Russell

AU - Brody, Jennifer

AU - Broeckel, Ulrich

AU - Broome, Jai

AU - Bunting, Karen

AU - Burchard, Esteban

AU - Cardwell, Jonathan

AU - Carty, Cara

AU - Casaburi, Richard

AU - Casella, James

AU - Chang, Christy

AU - Chasman, Daniel

AU - Chavan, Sameer

AU - Chen, Bo Juen

AU - Chen, Wei Min

AU - Chen, Yii Der Ida

AU - Cho, Michael

AU - Choi, Seung Hoan

AU - Chuang, Lee Ming

AU - Chung, Mina

AU - Cornell, Elaine

AU - Crandall, Carolyn

AU - Crapo, James

AU - Curran, Joanne

AU - Curtis, Jeffrey

AU - Custer, Brian

AU - Damcott, Coleen

AU - Darbar, Dawood

AU - Das, Sayantan

AU - David, Sean

AU - Davis, Colleen

AU - Daya, Michelle

AU - Andrade, Mariza De

AU - Debaun, Michael

AU - Deka, Ranjan

AU - Demeo, Dawn

AU - Devine, Scott

AU - Do, Ron

AU - Duan, Qing

AU - Duggirala, Ravi

AU - Durda, Peter

AU - Dutcher, Susan

AU - Eaton, Charles

AU - Ekunwe, Lynette

AU - Ellinor, Patrick

AU - Emery, Leslie

AU - Farber, Charles

AU - Farnam, Leanna

AU - Fingerlin, Tasha

AU - Flickinger, Matthew

AU - Fornage, Myriam

AU - Franceschini, Nora

AU - Fullerton, Stephanie M.

AU - Fulton, Lucinda

AU - Gabriel, Stacey

AU - Gan, Weiniu

AU - Gao, Yan

AU - Gass, Margery

AU - Gelb, Bruce

AU - Geng, Xiaoqi

AU - Germer, Soren

AU - Gignoux, Chris

AU - Gladwin, Mark

AU - Glahn, David

AU - Gogarten, Stephanie

AU - Gong, Da Wei

AU - Goring, Harald

AU - Gu, C. Charles

AU - Guan, Yue

AU - Guo, Xiuqing

AU - Haessler, Jeff

AU - Hall, Michael

AU - Harris, Daniel

AU - Hawley, Nicola

AU - He, Jiang

AU - Heavner, Ben

AU - Heckbert, Susan

AU - Hernandez, Ryan

AU - Herrington, David

AU - Hersh, Craig

AU - Hidalgo, Bertha

AU - Hixson, James

AU - Hokanson, John

AU - Hong, Elliott

AU - Hoth, Karin

AU - Hsiung, Chao

AU - Huston, Haley

AU - Hwu, Chii Min

AU - Irvin, Marguerite Ryan

AU - Jackson, Rebecca

AU - Jain, Deepti

AU - Jaquish, Cashell

AU - Jhun, Min A.

AU - Johnsen, Jill

AU - Johnson, Andrew

AU - Johnston, Rich

AU - Jones, Kimberly

AU - Kang, Hyun Min

AU - Kaplan, Robert C.

AU - Kardia, Sharon

AU - Kaufman, Laura

AU - Kelly, Shannon

AU - Kenny, Eimear

AU - Kessler, Michael

AU - Khan, Alyna

AU - Kinney, Greg

AU - Konkle, Barbara

AU - Kooperberg, Charles

AU - Kramer, Holly

AU - Krauter, Stephanie

AU - Lange, Christoph

AU - Lange, Ethan

AU - Lange, Leslie

AU - Laurie, Cathy

AU - Laurie, Cecelia

AU - Leboff, Meryl

AU - Lee, Seunggeun Shawn

AU - Lee, Wen Jane

AU - Lefaive, Jonathon

AU - Levine, David

AU - Levy, Dan

AU - Lewis, Joshua

AU - Li, Yun

AU - Lin, Honghuang

AU - Lin, Keng Han

AU - Liu, Simin

AU - Liu, Yongmei

AU - Loos, Ruth

AU - Lubitz, Steven

AU - Lunetta, Kathryn

AU - Luo, James

AU - Mahaney, Michael

AU - Make, Barry

AU - Manson, Jo Ann

AU - Margolin, Lauren

AU - Martin, Lisa

AU - Mathai, Susan

AU - Mathias, Rasika

AU - McArdle, Patrick

AU - McDonald, Merry Lynn

AU - McFarland, Sean

AU - McGarvey, Stephen

AU - Mei, Hao

AU - Meyers, Deborah A.

AU - Mikulla, Julie

AU - Min, Nancy

AU - Minear, Mollie

AU - Minster, Ryan L.

AU - Montasser, May E.

AU - Musani, Solomon

AU - Mwasongwe, Stanford

AU - Mychaleckyj, Josyf C.

AU - Nadkarni, Girish

AU - Naik, Rakhi

AU - Nekhai, Sergei

AU - Nickerson, Deborah

AU - North, Kari

AU - O'connell, Jeff

AU - O'connor, Tim

AU - Ochs-Balcom, Heather

AU - Pankow, James

AU - Papanicolaou, George

AU - Parker, Margaret

AU - Parsa, Afshin

AU - Penchev, Sara

AU - Peralta, Juan Manuel

AU - Perez, Marco

AU - Perry, James

AU - Peters, Ulrike

AU - Peyser, Patricia

AU - Phillips, Larry

AU - Phillips, Sam

AU - Pollin, Toni

AU - Becker, Julia Powers

AU - Boorgula, Meher Preethi

AU - Preuss, Michael

AU - Prokopenko, Dmitry

AU - Psaty, Bruce

AU - Qasba, Pankaj

AU - Qiao, Dandi

AU - Qin, Zhaohui

AU - Rafaels, Nicholas

AU - Raffield, Laura

AU - Rao, D. C.

AU - Rasmussen-Torvik, Laura

AU - Ratan, Aakrosh

AU - Redline, Susan

AU - Reed, Robert

AU - Regan, Elizabeth

AU - Reiner, Alex

AU - Rice, Ken

AU - Roden, Dan

AU - Roselli, Carolina

AU - Ruczinski, Ingo

AU - Russell, Pamela

AU - Ruuska, Sarah

AU - Sakornsakolpat, Phuwanat

AU - Salimi, Shabnam

AU - Salzberg, Steven

AU - Sandow, Kevin

AU - Sankaran, Vijay

AU - Scheller, Christopher

AU - Schmidt, Ellen

AU - Schwander, Karen

AU - Schwartz, David

AU - Sciurba, Frank

AU - Seidman, Christine

AU - Sheehan, Vivien

AU - Shetty, Amol

AU - Shetty, Aniket

AU - Sheu, Wayne Hui Heng

AU - Shoemaker, M. Benjamin

AU - Silver, Brian

AU - Silverman, Edwin

AU - Smith, Jennifer

AU - Smith, Josh

AU - Smith, Nicholas

AU - Smith, Tanja

AU - Smoller, Sylvia

AU - Snively, Beverly

AU - Sofer, Tamar

AU - Sotoodehnia, Nona

AU - Stilp, Adrienne

AU - Streeten, Elizabeth

AU - Sung, Yun Ju

AU - Sylvia, Jody

AU - Szpiro, Adam

AU - Sztalryd, Carole

AU - Taliun, Daniel

AU - Tang, Hua

AU - Taub, Margaret

AU - Taylor, Kent

AU - Taylor, Simeon

AU - Telen, Marilyn

AU - Thornton, Timothy A.

AU - Tinker, Lesley

AU - Tirschwell, David

AU - Tiwari, Hemant

AU - Tracy, Russell

AU - Vaidya, Dhananjay

AU - Vandehaar, Peter

AU - Vrieze, Scott

AU - Walker, Tarik

AU - Wallace, Robert

AU - Walts, Avram

AU - Wan, Emily

AU - Wang, Fei Fei

AU - Watson, Karol

AU - Weeks, Daniel E.

AU - Weir, Bruce

AU - Weiss, Scott

AU - Weng, Lu Chen

AU - Willer, Cristen

AU - Williams, Kayleen

AU - Williams, L. Keoki

AU - Wilson, Carla

AU - Wong, Quenna

AU - Xu, Huichun

AU - Yanek, Lisa

AU - Yang, Ivana

AU - Yang, Rongze

AU - Zaghloul, Norann

AU - Zhang, Yingze

AU - Zhao, Snow Xueyan

AU - Zhao, Wei

AU - Zheng, Xiuwen

AU - Zhi, Degui

AU - Zhou, Xiang

AU - Zody, Michael

AU - Zoellner, Sebastian

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.

AB - Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.

UR - http://www.scopus.com/inward/record.url?scp=85049751193&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049751193&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-04668-w

DO - 10.1038/s41467-018-04668-w

M3 - Article

C2 - 29973585

AN - SCOPUS:85049751193

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2606

ER -