Whole genome sequence analysis of blood lipid levels in >66,000 individuals-Reference-Cited by-同舟云学术

Whole genome sequence analysis of blood lipid levels in >66,000 individuals

Published:2022-10-11 Issue:1 Volume:13 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Selvaraj Margaret Sunitha^ORCID,Li Xihao^ORCID,Li Zilin^ORCID,Pampana Akhil^ORCID,Zhang David Y.^ORCID,Park Joseph^ORCID,Aslibekyan Stella,Bis Joshua C.^ORCID,Brody Jennifer A.^ORCID,Cade Brian E.^ORCID,Chuang Lee-Ming^ORCID,Chung Ren-Hua^ORCID,Curran Joanne E.^ORCID,de las Fuentes Lisa^ORCID,de Vries Paul S.,Duggirala Ravindranath,Freedman Barry I.^ORCID,Graff Mariaelisa^ORCID,Guo Xiuqing^ORCID,Heard-Costa Nancy^ORCID,Hidalgo Bertha,Hwu Chii-Min^ORCID,Irvin Marguerite R.,Kelly Tanika N.,Kral Brian G.^ORCID,Lange Leslie,Li Xiaohui,Lisa Martin^ORCID,Lubitz Steven A.^ORCID,Manichaikul Ani W.,Michael Preuss^ORCID,Montasser May E.^ORCID,Morrison Alanna C.^ORCID,Naseri Take,O’Connell Jeffrey R.,Palmer Nicholette D.^ORCID,Peyser Patricia A.^ORCID,Reupena Muagututia S.,Smith Jennifer A.^ORCID,Sun Xiao^ORCID,Taylor Kent D.,Tracy Russell P.,Tsai Michael Y.,Wang Zhe^ORCID,Wang Yuxuan^ORCID,Bao Wei,Wilkins John T.,Yanek Lisa R.^ORCID,Zhao Wei^ORCID,Arnett Donna K.^ORCID,Blangero John^ORCID,Boerwinkle Eric,Bowden Donald W.,Chen Yii-Der Ida,Correa Adolfo,Cupples L. Adrienne^ORCID,Dutcher Susan K.^ORCID,Ellinor Patrick T.^ORCID,Fornage Myriam^ORCID,Gabriel Stacey,Germer Soren^ORCID,Gibbs Richard,He Jiang,Kaplan Robert C.,Kardia Sharon L. R.,Kim Ryan,Kooperberg Charles^ORCID,Loos Ruth J. F.^ORCID,Viaud-Martinez Karine A,Mathias Rasika A.^ORCID,McGarvey Stephen T.^ORCID,Mitchell Braxton D.,Nickerson Deborah,North Kari E.^ORCID,Psaty Bruce M.^ORCID,Redline Susan,Reiner Alexander P.^ORCID,Vasan Ramachandran S.^ORCID,Rich Stephen S.^ORCID,Willer Cristen^ORCID,Rotter Jerome I.,Rader Daniel J.^ORCID,Lin Xihong^ORCID,Abe Namiko,Abecasis Gonçalo,Aguet Francois,Albert Christine,Almasy Laura,Alonso Alvaro,Ament Seth,Anderson Peter,Anugu Pramod,Applebaum-Bowden Deborah,Ardlie Kristin,Arking Dan,Ashley-Koch Allison,Assimes Tim,Auer Paul,Avramopoulos Dimitrios,Ayas Najib,Balasubramanian Adithya,Barnard John,Barnes Kathleen,Barr R. Graham,Barron-Casella Emily,Barwick Lucas,Beaty Terri,Beck Gerald,Becker Diane,Becker Lewis,Beer Rebecca,Beitelshees Amber,Benjamin Emelia,Benos Takis,Bezerra Marcos,Bielak Larry,Blackwell Thomas,Bowler Russell,Broeckel Ulrich,Broome Jai,Brown Deborah,Bunting Karen,Burchard Esteban,Bustamante Carlos,Buth Erin,Cardwell Jonathan,Carey Vincent,Carrier Julie,Carty Cara,Casaburi Richard,Romero Juan P. Casas,Casella James,Castaldi Peter,Chaffin Mark,Chang Christy,Chang Yi-Cheng,Chasman Daniel,Chavan Sameer,Chen Bo-Juen,Chen Wei-Min,Chen Yii-Der Ida,Cho Michael,Choi Seung Hoan,Chung Mina,Clish Clary,Comhair Suzy,Conomos Matthew,Cornell Elaine,Crandall Carolyn,Crapo James,Cupples L. Adrienne,Curtis Jeffrey,Custer Brian,Damcott Coleen,Darbar Dawood,David Sean,Davis Colleen,Daya Michelle,de Andrade Mariza,DeBaun Michael,Deka Ranjan,DeMeo Dawn,Devine Scott,Dinh Huyen,Doddapaneni Harsha,Duan Qing,Dugan-Perez Shannon,Duggirala Ravi,Durda Jon Peter,Eaton Charles,Ekunwe Lynette,Boueiz Adel El,Emery Leslie,Erzurum Serpil,Farber Charles,Farek Jesse,Fingerlin Tasha,Flickinger Matthew,Franceschini Nora,Frazar Chris,Fu Mao,Fullerton Stephanie M.,Fulton Lucinda,Gan Weiniu,Gao Shanshan,Gao Yan,Gass Margery,Geiger Heather,Gelb Bruce,Geraci Mark,Gerszten Robert,Ghosh Auyon,Gignoux Chris,Gladwin Mark,Glahn David,Gogarten Stephanie,Gong Da-Wei,Goring Harald,Graw Sharon,Gray Kathryn J.,Grine Daniel,Gross Colin,Gu C. Charles,Guan Yue,Gupta Namrata,Haas David M.,Haessler Jeff,Hall Michael,Han Yi,Hanly Patrick,Harris Daniel,Hawley Nicola L.,Heavner Ben,Heckbert Susan,Hernandez Ryan,Herrington David,Hersh Craig,Hidalgo Bertha,Hixson James,Hobbs Brian,Hokanson John,Hong Elliott,Hoth Karin,Hsiung Chao Agnes,Hu Jianhong,Hung Yi-Jen,Huston Haley,Hwu Chii Min,Jackson Rebecca,Jain Deepti,Jaquish Cashell,Johnsen Jill,Johnson Andrew,Johnson Craig,Johnston Rich,Jones Kimberly,Kang Hyun Min,Kelly Shannon,Kenny Eimear,Kessler Michael,Khan Alyna,Khan Ziad,Kim Wonji,Kimoff John,Kinney Greg,Konkle Barbara,Kramer Holly,Lange Christoph,Lange Ethan,Laurie Cathy,Laurie Cecelia,LeBoff Meryl,Lee Jiwon,Lee Sandra,Lee Wen-Jane,LeFaive Jonathon,Levine David,Levy Dan,Lewis Joshua,Li Yun,Lin Henry,Lin Honghuang,Liu Simin,Liu Yongmei,Liu Yu,Lunetta Kathryn,Luo James,Magalang Ulysses,Mahaney Michael,Make Barry,Manning Alisa,Manson JoAnn,Martin Lisa,Marton Melissa,Mathai Susan,May Susanne,McArdle Patrick,McDonald Merry-Lynn,McFarland Sean,McGoldrick Daniel,McHugh Caitlin,McNeil Becky,Mei Hao,Meigs James,Menon Vipin,Mestroni Luisa,Metcalf Ginger,Meyers Deborah A.,Mignot Emmanuel,Mikulla Julie,Min Nancy,Minear Mollie,Minster Ryan L.,Moll Matt,Momin Zeineen,Montgomery Courtney,Muzny Donna,Mychaleckyj Josyf C.,Nadkarni Girish,Naik Rakhi,Nekhai Sergei,Nelson Sarah C.,Neltner Bonnie,Nessner Caitlin,Nkechinyere Osuji,O’Connell Jeff,O’Connor Tim,Ochs-Balcom Heather,Okwuonu Geoffrey,Pack Allan,Paik David T.,Pankow James,Papanicolaou George,Parker Cora,Peralta Juan Manuel,Perez Marco,Perry James,Peters Ulrike,Phillips Lawrence S.,Pleiness Jacob,Pollin Toni,Post Wendy,Becker Julia Powers,Boorgula Meher Preethi,Preuss Michael,Qasba Pankaj,Qiao Dandi,Qin Zhaohui,Rafaels Nicholas,Raffield Laura,Rajendran Mahitha,Vasan Ramachandran S.,Rao D. C.,Rasmussen-Torvik Laura,Ratan Aakrosh,Reed Robert,Reeves Catherine,Regan Elizabeth,Reiner Alex,Rice Ken,Robillard Rebecca,Robine Nicolas,Roden Dan,Roselli Carolina,Ruczinski Ingo,Runnels Alexi,Russell Pamela,Ruuska Sarah,Ryan Kathleen,Sabino Ester Cerdeira,Saleheen Danish,Salimi Shabnam,Salvi Sejal,Salzberg Steven,Sandow Kevin,Sankaran Vijay G.,Santibanez Jireh,Schwander Karen,Schwartz David,Sciurba Frank,Seidman Christine,Seidman Jonathan,Sériès Frédéric,Sheehan Vivien,Sherman Stephanie L.,Shetty Amol,Shetty Aniket,Sheu Wayne Hui-Heng,Shoemaker M. Benjamin,Silver Brian,Silverman Edwin,Skomro Robert,Smith Albert Vernon,Smith Josh,Smith Nicholas,Smith Tanja,Smoller Sylvia,Snively Beverly,Snyder Michael,Sofer Tamar,Sotoodehnia Nona,Stilp Adrienne M.,Storm Garrett,Streeten Elizabeth,Su Jessica Lasky,Sung Yun Ju,Sylvia Jody,Szpiro Adam,Taliun Daniel,Tang Hua,Taub Margaret,Taylor Matthew,Taylor Simeon,Telen Marilyn,Thornton Timothy A.,Threlkeld Machiko,Tinker Lesley,Tirschwell David,Tishkoff Sarah,Tiwari Hemant,Tong Catherine,Vaidya Dhananjay,Berg David Van Den,VandeHaar Peter,Vrieze Scott,Walker Tarik,Wallace Robert,Walts Avram,Wang Fei Fei,Wang Heming,Wang Jiongming,Watson Karol,Watt Jennifer,Weeks Daniel E.,Weinstock Joshua,Weir Bruce,Weiss Scott T.,Weng Lu-Chen,Wessel Jennifer,Williams Kayleen,Williams L. Keoki,Wilson Carla,Wilson James,Winterkorn Lara,Wong Quenna,Wu Joseph,Xu Huichun,Yang Ivana,Yu Ketian,Zekavat Seyedeh Maryam,Zhang Yingze,Zhao Snow Xueyan,Zhao Wei,Zhu Xiaofeng,Zody Michael,Zoellner Sebastian,Peloso Gina M.^ORCID,Natarajan Pradeep^ORCID,

Abstract

AbstractBlood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.

Funder

U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

Link

https://www.nature.com/articles/s41467-022-33510-7.pdf

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