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

• DOI: 10.1038/s41467-018-04668-w
• Publication Date: 2018-06-28T10:48:57Z
• Authors: 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; Ramachandran S. V...; L. Adrienne Cupples; Jerome 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...; Laura Almasy; Alvaro Alonso; Seth Ament; Peter Anderson; Pramod Anugu; Deborah Applebaum...; Dan Arking; Donna K Arnett; Allison Ashley-Koch; Stella Aslibekyan; Tim Assimes; Paul Auer; Dimitrios Avramop...; 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. Full...; 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 I...; Rebecca Jackson; Deepti Jain; Cashell Jaquish; Min A Jhun; Jill Johnsen; Andrew Johnson; Rich Johnston; Kimberly Jones; Hyun Min Kang; Robert 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; JoAnn 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 Boo...; Michael Preuss; Dmitry Prokopenko; Bruce Psaty; Pankaj Qasba; Dandi Qiao; Zhaohui Qin; Nicholas Rafaels; Laura Raffield; D. C. Rao; Laura Rasmussen-T...; Aakrosh Ratan; Susan Redline; Robert Reed; Elizabeth Regan; Alex Reiner; Ken Rice; Dan Roden; Carolina Roselli; Ingo Ruczinski; Pamela Russell; Sarah Ruuska; Phuwanat Sakornsa...; 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 Shoem...; 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
• Keywords: 0301 basic medicine; DNA Copy Number Variations; Science; Quantitative Trait Loci; 610; Black People; Gene Expression; Cardiovascular; Polymorphism, Single Nucleotide; Article; White People; LDL; 03 medical and health sciences; Risk Factors; 616; Genetics; 2.1 Biological and endogenous factors; Humans; Polymorphism; Aetiology; Genome; Whole Genome Sequencing; Genome, Human; Prevention; Human Genome; Q; Adaptor Proteins; Single Nucleotide; Cholesterol, LDL; Atherosclerosis; NHLBI TOPMed Lipids Working Group; 3. Good health; Vesicular Transport; Black or African American; Adaptor Proteins, Vesicular Transport; Cholesterol; Heart Disease; Good Health and Well Being; Cardiovascular Diseases; Human; Genome-Wide Association Study; Lipoprotein(a)

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