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.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

Details

Title
Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries
Author
Zekavat, Seyedeh M 1   VIAFID ORCID Logo  ; Ruotsalainen Sanni 2 ; Handsaker, Robert E 3   VIAFID ORCID Logo  ; Alver Maris 4 ; Bloom, Jonathan 5   VIAFID ORCID Logo  ; Poterba, Timothy 5 ; Seed Cotton 5 ; Ernst, Jason 6   VIAFID ORCID Logo  ; Chaffin, Mark 7 ; Engreitz Jesse 7   VIAFID ORCID Logo  ; Peloso, Gina M 8 ; Manichaikul Ani 9 ; Yang Chaojie 9 ; Ryan, Kathleen A 10 ; Fu Mao 10 ; Craig, Johnson W 11 ; Tsai, Michael 12 ; Budoff, Matthew 13 ; Vasan, Ramachandran S 14 ; Adrienne, Cupples L 15 ; Rotter, Jerome I 16 ; Rich, Stephen S 9 ; Post, Wendy 17 ; Mitchell, Braxton D 18 ; Correa, Adolfo 19   VIAFID ORCID Logo  ; Metspalu Andres 20 ; Wilson, James G 19 ; Salomaa Veikko 21 ; Kellis Manolis 22 ; Daly, Mark J 23 ; Neale, Benjamin M 23   VIAFID ORCID Logo  ; McCarroll, Steven 3 ; Surakka Ida 2 ; Tonu, Esko 24   VIAFID ORCID Logo  ; Ganna, Andrea 23 ; Ripatti Samuli 25 ; Sekar, Kathiresan 26   VIAFID ORCID Logo  ; Natarajan Pradeep 26   VIAFID ORCID Logo  ; Abe Namiko 27 ; Abecasis Goncalo 28 ; Albert, Christine 29 ; Allred Nicholette (Nichole) Palmer 30 ; Almasy, Laura 31 ; Alonso, Alvaro 32 ; Ament, Seth 33 ; Anderson, Peter 34 ; Anugu Pramod 35 ; Applebaum-Bowden, Deborah 36 ; Arking, Dan 37 ; Arnett, Donna K 38 ; Ashley-Koch, Allison 39 ; Aslibekyan Stella 40 ; Assimes, Tim 41 ; Auer, Paul 42 ; Avramopoulos Dimitrios 37 ; Barnard, John 43 ; Barnes, Kathleen 44 ; Graham, Barr R 45 ; Barron-Casella, Emily 37 ; Beaty, Terri 37 ; Becker, Diane 37 ; Becker, Lewis 37 ; Beer, Rebecca 36 ; Begum Ferdouse 37 ; Beitelshees Amber 33 ; Emelia, Benjamin 46 ; Bezerra Marcos 47 ; Bielak, Larry 28 ; Bis Joshua 34 ; Blackwell, Thomas 28 ; Blangero, John 48 ; Boerwinkle, Eric 49 ; Borecki Ingrid 34 ; Bowler, Russell 50 ; Brody, Jennifer 34 ; Broeckel Ulrich 51 ; Broome Jai 34 ; Bunting, Karen 27 ; Burchard Esteban 52 ; Cardwell, Jonathan 44 ; Carty, Cara 53 ; Casaburi, Richard 54 ; Casella, James 37 ; Chang, Christy 33 ; Chasman, Daniel 55 ; Chavan Sameer 44 ; Bo-Juen, Chen 27 ; Wei-Min, Chen 56 ; Chen Yii-Der Ida 57 ; Cho, Michael 55 ; Choi, Seung Hoan 58 ; Lee-Ming, Chuang 59 ; Chung, Mina 43 ; Cornell, Elaine 60 ; Crandall, Carolyn 54 ; Crapo, James 50 ; Curran, Joanne 48 ; Curtis, Jeffrey 28 ; Custer, Brian 61 ; Damcott Coleen 33 ; Darbar Dawood 62 ; Das Sayantan 28 ; David, Sean 41 ; Davis, Colleen 34 ; Daya, Michelle 44 ; Andrade, Mariza de 63 ; DeBaun, Michael 64 ; Deka Ranjan 65 ; DeMeo, Dawn 55 ; Devine, Scott 33 ; Do, Ron 66 ; Duan Qing 67 ; Duggirala Ravi 68 ; Durda, Peter 60 ; Dutcher, Susan 69 ; Eaton, Charles 70 ; Ekunwe Lynette 35 ; Ellinor, Patrick 29 ; Emery, Leslie 34 ; Farber, Charles 56 ; Farnam Leanna 55 ; Fingerlin Tasha 50 ; Flickinger, Matthew 28 ; Fornage Myriam 49 ; Franceschini, Nora 67 ; Fullerton, Stephanie M 34 ; Fulton, Lucinda 69 ; Gabriel, Stacey 58 ; Gan Weiniu 36 ; Gao, Yan 35 ; Gass Margery 71 ; Gelb, Bruce 66 ; Geng Xiaoqi (Priscilla) 28 ; Germer Soren 27 ; Gignoux, Chris 41 ; Gladwin, Mark 72 ; Glahn, David 73 ; Gogarten Stephanie 34 ; Da-Wei, Gong 33 ; Goring Harald 74 ; Charles, Gu C 69 ; Guan Yue 33 ; Guo Xiuqing 57 ; Haessler, Jeff 75 ; Hall, Michael 35 ; Harris, Daniel 33 ; Hawley, Nicola 73 ; He, Jiang 76 ; Heavner, Ben 34 ; Heckbert, Susan 34 ; Hernandez, Ryan 52 ; Herrington, David 30 ; Hersh, Craig 55 ; Hidalgo Bertha 40 ; Hixson, James 49 ; Hokanson, John 44 ; Elliott, Hong 33 ; Hoth, Karin 77 ; Hsiung Chao (Agnes) 78 ; Huston Haley 79 ; Hwu, Chii Min 80 ; Ryan, Irvin Marguerite 40 ; Jackson, Rebecca 81 ; Jain Deepti 34 ; Cashell, Jaquish 36 ; Jhun, Min A 28 ; Johnsen, Jill 82 ; Johnson, Andrew 83 ; Johnston, Rich 32 ; Jones, Kimberly 37 ; Kang, Hyun Min 28 ; Kaplan, Robert 84 ; Kardia, Sharon 28 ; Kaufman, Laura 55 ; Kelly, Shannon 61 ; Kenny Eimear 66 ; Kessler, Michael 33 ; Khan Alyna 34 ; Kinney, Greg 44 ; Konkle, Barbara 85 ; Kooperberg, Charles 71 ; Kramer, Holly 86 ; Krauter, Stephanie 34 ; Lange, Christoph 87 ; Lange, Ethan 44 ; Lange, Leslie 44 ; Laurie, Cathy 34 ; Laurie Cecelia 34 ; LeBoff Meryl 55 ; Lee, Seunggeun Shawn 28 ; Wen-Jane, Lee 80 ; LeFaive Jonathon 28 ; Levine, David 34 ; Levy, Dan 83 ; Lewis, Joshua 33 ; Li, Yun 67 ; Lin Honghuang 88 ; Lin Keng Han 28 ; Liu, Simin 89 ; Liu, Yongmei 30 ; Loos, Ruth 66 ; Lubitz, Steven 29 ; Lunetta, Kathryn 88 ; Luo, James 83 ; Mahaney, Michael 48 ; Make Barry 37 ; Manson, JoAnn 55 ; Margolin, Lauren 58 ; Martin, Lisa 90 ; Mathai, Susan 44 ; Mathias Rasika 37 ; McArdle, Patrick 33 ; Merry-Lynn, McDonald 40 ; McFarland, Sean 91 ; McGarvey, Stephen 70 ; Hao, Mei 35 ; Meyers, Deborah A 92 ; Mikulla, Julie 36 ; Min, Nancy 35 ; Minear Mollie 36 ; Minster, Ryan L 72 ; Montasser, May E 33 ; Musani Solomon 35 ; Stanford, Mwasongwe 35 ; Mychaleckyj, Josyf C 56 ; Nadkarni Girish 66 ; Naik Rakhi 37 ; Nekhai Sergei 93 ; Nickerson, Deborah 34 ; North, Kari 67 ; O’Connell Jeff 33 ; O’Connor Tim 33 ; Ochs-Balcom, Heather 94 ; Pankow, James 95 ; Papanicolaou, George 36 ; Parker, Margaret 55 ; Parsa Afshin 33 ; Penchev, Sara 50 ; Peralta, Juan Manuel 68 ; Perez, Marco 41 ; Perry, James 33 ; Peters, Ulrike 96 ; Peyser, Patricia 28 ; Phillips, Larry 32 ; Phillips, Sam 34 ; Pollin Toni 33 ; Becker, Julia Powers 44 ; Boorgula Meher Preethi 44 ; Preuss, Michael 66 ; Prokopenko Dmitry 91 ; Psaty, Bruce 34 ; Qasba Pankaj 36 ; Qiao Dandi 55 ; Qin Zhaohui 32 ; Rafaels Nicholas 44 ; Raffield, Laura 67 ; Rao, D C 69 ; Rasmussen-Torvik, Laura 97 ; Aakrosh, Ratan 56 ; Redline, Susan 55 ; Reed, Robert 33 ; Regan, Elizabeth 50 ; Reiner, Alex 96 ; Rice, Ken 34 ; Roden, Dan 64 ; Roselli, Carolina 58 ; Ruczinski Ingo 37 ; Russell, Pamela 44 ; Ruuska, Sarah 85 ; Phuwanat, Sakornsakolpat 55 ; Salimi Shabnam 33 ; Salzberg, Steven 37 ; Sandow, Kevin 57 ; Sankaran Vijay 91 ; Scheller, Christopher 28 ; Schmidt, Ellen 28 ; Schwander, Karen 69 ; Schwartz, David 44 ; Sciurba, Frank 72 ; Seidman, Christine 98 ; Sheehan, Vivien 99 ; Shetty Amol 33 ; Shetty Aniket 44 ; Sheu, Wayne Hui-Heng 80 ; Benjamin, Shoemaker M 64 ; Silver, Brian 100 ; Silverman, Edwin 55 ; Smith, Jennifer 28 ; Smith, Josh 34 ; Smith, Nicholas 34 ; Smith, Tanja 27 ; Smoller, Sylvia 84 ; Snively, Beverly 30 ; Sofer Tamar 55 ; Sotoodehnia Nona 34 ; Stilp Adrienne 34 ; Streeten, Elizabeth 33 ; Sung Yun Ju 69 ; Sylvia, Jody 55 ; Szpiro, Adam 34 ; Sztalryd Carole 33 ; Taliun, Daniel 101 ; Tang, Hua 41 ; Taub, Margaret 37 ; Taylor, Kent 57 ; Taylor, Simeon 33 ; Telen Marilyn 39 ; Thornton, Timothy A 34 ; Tinker, Lesley 53 ; Tirschwell, David 34 ; Tiwari Hemant 40 ; Russell, Tracy 60 ; Vaidya Dhananjay 37 ; VandeHaar, Peter 28 ; Vrieze, Scott 102 ; Walker, Tarik 44 ; Wallace, Robert 77 ; Walts Avram 44 ; Wan, Emily 55 ; Wang, Fei Fei 34 ; Watson, Karol 54 ; Weeks, Daniel E 72 ; Weir, Bruce 34 ; Weiss, Scott 55 ; Lu-Chen, Weng 29 ; Willer Cristen 28 ; Williams, Kayleen 34 ; Keoki, Williams L 103 ; Wilson, Carla 55 ; Wong Quenna 34 ; Xu, Huichun 33 ; Yanek, Lisa 37 ; Yang, Ivana 44 ; Yang Rongze 33 ; Zaghloul Norann 33 ; Zhang, Yingze 72 ; Zhao Snow Xueyan 50 ; Zhao, Wei 28 ; Zheng Xiuwen 34 ; Degui, Zhi 49 ; Zhou, Xiang 28 ; Zody, Michael 27 ; Zoellner, Sebastian 28 

1  Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34); Yale School of Medicine, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710); Yale University, Department of Computational Biology & Bioinformatics, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
2  University of Helsinki, Institute for Molecular Medicine, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
3  Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34); Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, USA (GRID:grid.66859.34); Harvard Medical School, Department of Genetics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
4  University of Tartu, Department of Biotechnology, Institute of Molecular and Cell Biology, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661); Estonian Genome Center, Tallinn, Estonia (GRID:grid.10939.32) 
5  Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34); Analytic and Translational Genetics Unit, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
6  University of California, Los Angeles, Department of Biological Chemistry, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718) 
7  Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34) 
8  Boston University School of Public Health, Department of Biostatistics, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558) 
9  University of Virginia, Center for Public Health Genomics, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
10  University of Maryland School of Medicine, Program in Personalized and Genomic Medicine, Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, Baltimore, USA (GRID:grid.411024.2) (ISNI:0000 0001 2175 4264) 
11  University of Washington, Department of Biostatistics, School of Public Health and Community Medicine, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
12  University of Minnesota, Department of Laboratory Medicine and Pathology, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657) 
13  Los Angeles Biomedical Research Institute, Division of Cardiology, Harbor-UCLA Medical Center, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718) 
14  NHLBI Framingham Heart Study, Framingham, USA (GRID:grid.19006.3e); Boston university Schools of Medicine and Public health, Sections of Preventive medicine and Epidemiology, and cardiovascular medicine, Departments of Medicine and Epidemiology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558) 
15  Boston University School of Public Health, Department of Biostatistics, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); NHLBI Framingham Heart Study, Framingham, USA (GRID:grid.189504.1) 
16  Harbor-UCLA Medical Center, Departments of Pediatrics and Medicine, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, USA (GRID:grid.239844.0) (ISNI:0000 0001 0157 6501) 
17  Johns Hopkins University School of Medicine, Division of Cardiology, Department of Medicine, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
18  University of Maryland School of Medicine, Department of Medicine, Baltimore, USA (GRID:grid.411024.2) (ISNI:0000 0001 2175 4264) 
19  University of Mississippi Medical Center, Department of Medicine, Jackson, USA (GRID:grid.410721.1) (ISNI:0000 0004 1937 0407) 
20  Estonian Genome Center, Tallinn, Estonia (GRID:grid.410721.1) 
21  National Institute for Health and Welfare, Helsinki, Finland (GRID:grid.14758.3f) (ISNI:0000 0001 1013 0499) 
22  Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34); Massachusetts Institute of Technology, Computer Science and Artificial Intelligence Lab, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786) 
23  Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34); Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, USA (GRID:grid.66859.34); Analytic and Translational Genetics Unit, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
24  Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34); Estonian Genome Center, Tallinn, Estonia (GRID:grid.66859.34) 
25  Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34); University of Helsinki, Institute for Molecular Medicine, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); University of Helsinki, Department of Public Health, Faculty of Medicine, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
26  Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34); Harvard Medical School, Department of Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Massachusetts General Hospital, Center for Genomic Medicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Massachusetts General Hospital, Cardiovascular Research Center, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
27  New York Genome Center, New York, USA (GRID:grid.429884.b) 
28  University of Michigan, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
29  Massachusetts General Hospital, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
30  Wake Forest Baptist Health, Winston-Salem, USA (GRID:grid.412860.9) (ISNI:0000 0004 0459 1231) 
31  University of Pennsylvania, Children’s Hospital of Philadelphia, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); University of Pennsylvania, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
32  Emory University, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
33  University of Maryland, Baltimore, USA (GRID:grid.411024.2) (ISNI:0000 0001 2175 4264) 
34  University of Washington, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
35  University of Mississippi, Jackson, USA (GRID:grid.251313.7) (ISNI:0000 0001 2169 2489) 
36  National Institutes of Health, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
37  Johns Hopkins University, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
38  University of Kentucky, Lexington, USA (GRID:grid.266539.d) (ISNI:0000 0004 1936 8438) 
39  Duke University, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961) 
40  University of Alabama, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000000106344187) 
41  Stanford University, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
42  University of Wisconsin Milwaukee, Milwaukee, USA (GRID:grid.267468.9) (ISNI:0000 0001 0695 7223) 
43  Cleveland Clinic, Cleveland, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725) 
44  University of Colorado, Denver, USA (GRID:grid.241116.1) (ISNI:0000000107903411) 
45  Columbia University, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
46  Boston University, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Massachusetts General Hospital, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
47  Fundação de Hematologia e Hemoterapia de Pernambuco - Hemope, Recife, Brazil (GRID:grid.32224.35) 
48  University of Texas Rio Grande Valley School of Medicine, Brownsville, USA (GRID:grid.449717.8) (ISNI:0000 0004 5374 269X) 
49  University of Texas Health, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401) 
50  National Jewish Health, Denver, USA (GRID:grid.240341.0) (ISNI:0000 0004 0396 0728) 
51  Medical College of Wisconsin, Milwaukee, USA (GRID:grid.30760.32) (ISNI:0000 0001 2111 8460) 
52  University of California, San Francisco, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
53  Women’s Health Initiative, Seattle, USA (GRID:grid.453840.e) 
54  University of California, Los Angeles, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718) 
55  Brigham & Women’s Hospital, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
56  University of Virginia, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
57  Los Angeles Biomedical Research Institute, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718) 
58  The Broad Institute, Cambridge, USA (GRID:grid.66859.34) 
59  National Taiwan University, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241) 
60  University of Vermont, Burlington, USA (GRID:grid.59062.38) (ISNI:0000 0004 1936 7689) 
61  Blood Systems Research Institute UCSF, San Francisco, USA (GRID:grid.280902.1) (ISNI:0000 0004 0395 6091) 
62  University of Illinois at Chicago, Chicago, USA (GRID:grid.185648.6) (ISNI:0000 0001 2175 0319) 
63  Mayo Clinic, Rochester, USA (GRID:grid.66875.3a) (ISNI:0000 0004 0459 167X) 
64  Vanderbilt University, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
65  University of Cincinnati, Cincinnati, USA (GRID:grid.24827.3b) (ISNI:0000 0001 2179 9593) 
66  Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
67  University of North Carolina, Chapel Hill, USA (GRID:grid.410711.2) (ISNI:0000 0001 1034 1720) 
68  University of Texas Rio Grande Valley School of Medicine, Edinburg, USA (GRID:grid.449717.8) (ISNI:0000 0004 5374 269X) 
69  Washington University in St Louis, St Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
70  Brown University, Providence, USA (GRID:grid.40263.33) (ISNI:0000 0004 1936 9094) 
71  Fred Hutchinson Cancer Research Center, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622) 
72  University of Pittsburgh, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000) 
73  Yale University, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
74  University of Texas Rio Grande Valley School of Medicine, San Antonio, USA (GRID:grid.215352.2) (ISNI:0000000121845633) 
75  Fred Hutchinson Cancer Research Center, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); Women’s Health Initiative, Seattle, USA (GRID:grid.453840.e) 
76  Tulane University, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588) 
77  University of Iowa, Iowa City, USA (GRID:grid.214572.7) (ISNI:0000 0004 1936 8294) 
78  National Health Research Institute Taiwan, Zhunan Township, Taiwan (GRID:grid.59784.37) (ISNI:0000000406229172) 
79  Blood Works Northwest, Seattle, USA (GRID:grid.59784.37) 
80  Taichung Veterans General Hospital Taiwan, Taichung City, Taiwan (GRID:grid.410764.0) (ISNI:0000 0004 0573 0731) 
81  Ohio State University Wexner Medical Center, Columbus, USA (GRID:grid.412332.5) (ISNI:0000 0001 1545 0811) 
82  Blood Works Northwest, Seattle, USA (GRID:grid.214458.e); University of Washington, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
83  NIH National Heart, Lung, and Blood Institute, Bethesda, USA (GRID:grid.279885.9) (ISNI:0000 0001 2293 4638) 
84  Albert Einstein College of Medicine, New York, USA (GRID:grid.251993.5) (ISNI:0000000121791997) 
85  Blood Works Northwest, Seattle, USA (GRID:grid.241116.1) 
86  Loyola University, Maywood, USA (GRID:grid.164971.c) (ISNI:0000 0001 1089 6558) 
87  Harvard School of Public Health, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
88  Boston University, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558) 
89  Brown University, Providence, USA (GRID:grid.40263.33) (ISNI:0000 0004 1936 9094); Women’s Health Initiative, Seattle, USA (GRID:grid.453840.e) 
90  George Washington University, Washington, USA (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
91  Harvard University, Cambridge, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
92  University of Arizona, Tucson, USA (GRID:grid.134563.6) (ISNI:0000 0001 2168 186X) 
93  Howard University, Washington, USA (GRID:grid.257127.4) (ISNI:0000 0001 0547 4545) 
94  University at Buffalo, Buffalo, USA (GRID:grid.273335.3) (ISNI:0000 0004 1936 9887) 
95  University of Minnesota, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657) 
96  Fred Hutchinson Cancer Research Center, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); University of Washington, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
97  Northwestern University, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507) 
98  Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
99  Baylor College of Medicine, Houston, USA (GRID:grid.39382.33) (ISNI:0000 0001 2160 926X) 
100  UMass Memorial Medical Center, Worcester, USA (GRID:grid.416999.a) (ISNI:0000 0004 0591 6261) 
101  Baylor College of Medicine, Ann Arbor, USA (GRID:grid.39382.33) (ISNI:0000 0001 2160 926X) 
102  University of Minnesota, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657); University of Colorado at Boulder, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564) 
103  Henry Ford Health System, Detroit, USA (GRID:grid.239864.2) (ISNI:0000 0000 8523 7701) 
Publication year
2018
Publication date
Dec 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-04668-w
ProQuest document ID
2064230099
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.