Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals
Authors: Tahir Usman A. , Katz Daniel H. , Avila-Pachecho Julian , Bick Alexander G. , Pampana Akhil , Robbins Jeremy M. , Yu Zhi , Chen Zsu-Zsu , Benson Mark D. , Cruz Daniel E. , Ngo Debby , Deng Shuliang , Shi Xu , Zheng Shuning , Eisman Aaron S. , Farrell Laurie , Hall Michael E. , Correa Adolfo , Tracy Russell P. , Durda Peter , Taylor Kent D. , Liu Yongmei , Johnson W. Craig , Guo Xiuqing , Yao Jie , Chen Yii-Der Ida , Manichaikul Ani W. , Ruberg Frederick L. , Blaner William S. , Jain Deepti ,   NHLBI Trans-Omics for Precision Medicine 1 Consortium, Abe Namiko , Abecasis GonÃ§alo , Aguet Francois , Albert Christine , Almasy Laura , Alonso Alvaro , Ament Seth , Anderson Peter , Anugu Pramod , Applebaum-Bowden Deborah , Ardlie Kristin , Arking Dan , Arnett Donna K. , Ashley-Koch Allison , Aslibekyan Stella , 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 , Bis Joshua , Blackwell Thomas , Blangero John , Blue Nathan , Boerwinkle Eric , Bowden Donald W. , Bowler Russell , Brody Jennifer , Broeckel Ulrich , Broome Jai , Brown Deborah , Bunting Karen , Burchard Esteban , Bustamante Carlos , Buth Erin , Cade Brian , Cardwell Jonathan , Carey Vincent , Carrier Julie , Carson April , 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 , Cho Michael , Choi Seung Hoan , Chuang Lee-Ming , Chung Mina , Chung Ren-Hua , Comhair Suzy , Conomos Matthew , Cornell Elaine , Crandall Carolyn , Crapo James , Cupples L. Adrienne , Curran Joanne , Curtis Jeffrey , Custer Brian , Damcott Coleen , Darbar Dawood , David Sean , Davis Colleen , Daya Michelle , de Andrade Mariza , Fuentes Lisa de las , de Vries Paul , DeBaun Michael , Deka Ranjan , DeMeo Dawn , Devine Scott , Dinh Huyen , Doddapaneni Harsha , Duan Qing , Dugan-Perez Shannon , Duggirala Ravi , Dutcher Susan K. , Eaton Charles , Ekunwe Lynette , El Boueiz Adel , Ellinor Patrick , Emery Leslie , Erzurum Serpil , Farber Charles , Farek Jesse , Fingerlin Tasha , Flickinger Matthew , Fornage Myriam , Franceschini Nora , Frazar Chris , Fu Mao , Fullerton Stephanie M. , Fulton Lucinda , Gabriel Stacey , Gan Weiniu , Gao Shanshan , Gao Yan , Gass Margery , Geiger Heather , Gelb Bruce , Geraci Mark , Germer Soren , Ghosh Auyon , Gibbs Richard , 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 , Haessler Jeff , Han Yi , Hanly Patrick , Harris Daniel , Hawley Nicola L. , He Jiang , Heavner Ben , Heckbert Susan , Hernandez Ryan , Herrington David , Hersh Craig , Hidalgo Bertha , Hixson James , Hobbs Brian , Hokanson John , Hong Elliott , Hoth Karin , Hsiung Chao , Hu Jianhong , Hung Yi-Jen , Huston Haley , Hwu Chii Min , Irvin Marguerite Ryan , Jackson Rebecca , Jaquish Cashell , Johnsen Jill , Johnson Andrew , Johnston Rich , Jones Kimberly , Kang Hyun Min , Kaplan Robert , Kardia Sharon , Kelly Shannon , Kenny Eimear , Kessler Michael , Khan Alyna , Khan Ziad , Kim Wonji , Kimoff John , Kinney Greg , Konkle Barbara , Kooperberg Charles , Kramer Holly , Lange Christoph , Lange Ethan , Lange Leslie , Laurie Cathy , Laurie Cecelia , LeBoff Meryl , Lee Jiwon , Lee Sandra , Lee Wen-Jane , LeFaive Jonathon , Levine David , Levy Dan , Lewis Joshua , Li Xiaohui , Li Yun , Lin Henry , Lin Honghuang , Lin Xihong , Liu Simin , Liu Yu , Loos Ruth J. F. , Lubitz Steven , Lunetta Kathryn , Luo James , Magalang Ulysses , Mahaney Michael , Make Barry , Manning Alisa , Manson JoAnn , Martin Lisa , Marton Melissa , Mathai Susan , Mathias Rasika , May Susanne , McArdle Patrick , McDonald Merry-Lynn , McFarland Sean , McGarvey Stephen , 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. , Mitchell Braxton D. , Moll Matt , Momin Zeineen , Montasser May E. , Montgomery Courtney , Muzny Donna , Mychaleckyj Josyf C. , Nadkarni Girish , Naik Rakhi , Naseri Take , Nekhai Sergei , Nelson Sarah C. , Neltner Bonnie , Nessner Caitlin , Nickerson Deborah , Nkechinyere Osuji , North Kari , O’Connell Jeff , O’Connor Tim , Ochs-Balcom Heather , Okwuonu Geoffrey , Pack Allan , Paik David T. , Palmer Nicholette , Pankow James , Papanicolaou George , Parker Cora , Peloso Gina , Peralta Juan Manuel , Perez Marco , Perry James , Peters Ulrike , Peyser Patricia , Phillips Lawrence S. , Pleiness Jacob , Pollin Toni , Post Wendy , Becker Julia Powers , Boorgula Meher Preethi , Preuss Michael , Psaty Bruce , Qasba Pankaj , Qiao Dandi , Qin Zhaohui , Rafaels Nicholas , Raffield Laura , Rajendran Mahitha , Ramachandran Vasan S. , Rao D. C. , Rasmussen-Torvik Laura , Ratan Aakrosh , Redline Susan , Reed Robert , Reeves Catherine , Regan Elizabeth , Reiner Alex , Reupena Muagututiâ€ã Sefuiva , Rice Ken , Robillard Rebecca , Robine Nicolas , Dan Roden  , Roselli Carolina , Ruczinski Ingo , Runnels Alexi , Russell Pamela , Ruuska Sarah , 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 , SÃ©riÃ¨s FrÃ©dÃ©ric , 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 Jennifer , 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 , Tsai Michael , Vaidya Dhananjay , Van Den Berg David , 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 , Willer Cristen , Williams Kayleen , Williams L. Keoki , Wilson Carla , Winterkorn Lara , Wong Quenna , Wu Joseph , Xu Huichun , Yanek Lisa , Yang Ivana , Yu Ketian , Zekavat Seyedeh Maryam , Zhang Yingze , Zhao Snow Xueyan , Zhao Wei , Zhu Xiaofeng , Ziv Elad , Zody Michael , Zoellner Sebastian , Bouchard Claude , Sarzynski Mark A. , Rich Stephen S. , Rotter Jerome I. , Wang Thomas J. , Wilson James G. , Clish Clary B. , Natarajan Pradeep , Gerszten Robert E. 
Published: August 2022

AbstractIntegrating genetic information with metabolomics has provided new insights into genes affecting human metabolism. However, gene-metabolite integration has been primarily studied in individuals of European Ancestry, limiting the opportunity to leverage genomic diversity for discovery. In addition, these analyses have principally involved known metabolites, with the majority of the profiled peaks left unannotated. Here, we perform a whole genome association study of 2,291 metabolite peaks (known and unknown features) in 2,466 Black individuals from the Jackson Heart Study. We identify 519 locus-metabolite associations for 427 metabolite peaks and validate our findings in two multi-ethnic cohorts. A significant proportion of these associations are in ancestry specific alleles including findings in APOE, TTR and CD36. We leverage tandem mass spectrometry to annotate unknown metabolites, providing new insight into hereditary diseases including transthyretin amyloidosis and sickle cell disease. Our integrative omics approach leverages genomic diversity to provide novel insights into diverse cardiometabolic diseases.