Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals
Usman A. Tahir, Daniel H. Katz, Julián Ávila-Pacheco, Alexander G. Bick, Akhil Pampana, Jeremy Robbins, Zhi Yu, Zsu‐Zsu Chen, Mark D. Benson, Daniel E. Cruz, Debby Ngo, Shuliang Deng, Xu Shi, Shuning Zheng, Aaron S. Eisman, Laurie Farrell, Michael E. Hall, Adolfo Correa, Russell P. Tracy, Peter Durda, Kent D. Taylor, Ching‐Ti Liu, W. Craig Johnson, Xiuqing Guo, Jie Yao, Yii‐Der Ida Chen, Ani Manichaikul, Frederick L. Ruberg, William S. Blaner, Deepti Jain, Namiko Abe, Gonçalo Abecasis, François Aguet, Christine M. Albert, Laura Almasy, Álvaro Alonso, Seth A. Ament, Peter Anderson, Pramod Anugu, Deborah Applebaum‐Bowden, Kristin Ardlie, Dan E. Arking, Donna K. Arnett, Allison E. Ashley‐Koch, Stella Aslibekyan, Tim Assimes, Paul L. Auer, Dimitrios Avramopoulos, Najib Ayas, Adithya Balasubramanian, John Barnard, Kathleen C. Barnes, R. Graham Barr, Emily Barron‐Casella, Lucas Barwick, Terri H. Beaty, Gerald J. Beck, Diane M. Becker, Lewis C. Becker, Rebecca Beer, Amber L. Beitelshees, Emelia J. Benjamin, Takis Benos, Marcos Bezerra, Larry Bielak, Joshua C. Bis, Thomas W. Blackwell, John Blangero, Nathan R. Blue, Eric Boerwinkle, Donald W. Bowden, Russell P. Bowler, Jennifer A. Brody, Ulrich Broeckel, Jai Broome, Deborah Brown, Karen Bunting, Esteban G. Burchard, Carlos D. Bustamante, Erin Buth, Brian E. Cade, Jonathan Cardwell, Vincent J. Carey, Julie Carrier, April P. Carson, Cara L. Carty, Richard Casaburi, Juan P. Romero, James F. Casella, Peter J. Castaldi, Mark Chaffin, Christy Chang, Yi‐Cheng Chang, Daniel I. Chasman, Sameer Chavan, Bo‐Juen Chen, Wei‐Min Chen, Michael Cho, Seung Hoan Choi, Lee‐Ming Chuang
Abstract
Integrating 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.