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2. Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks

Author

Perry, Andrew S., Farber-Eger, Eric, Gonzales, Tomas, Tanaka, Toshiko, Robbins, Jeremy M., Murthy, Venkatesh L., Stolze, Lindsey K., Zhao, Shilin, Huang, Shi, Colangelo, Laura A., Deng, Shuliang, Hou, Lifang, Lloyd-Jones, Donald M., Walker, Keenan A., Ferrucci, Luigi, Watts, Eleanor L., Barber, Jacob L., Rao, Prashant, Mi, Michael Y., Gabriel, Kelley Pettee, Hornikel, Bjoern, Sidney, Stephen, Houstis, Nicholas, Lewis, Gregory D., Liu, Gabrielle Y., Thyagarajan, Bharat, Khan, Sadiya S., Choi, Bina, Washko, George, Kalhan, Ravi, Wareham, Nick, Bouchard, Claude, Sarzynski, Mark A., Gerszten, Robert E., Brage, Soren, Wells, Quinn S., Nayor, Matthew, and Shah, Ravi V.

Published
2024
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3. Protein-metabolite association studies identify novel proteomic determinants of metabolite levels in human plasma

Author

Benson, Mark D, Eisman, Aaron S, Tahir, Usman A, Katz, Daniel H, Deng, Shuliang, Ngo, Debby, Robbins, Jeremy M, Hofmann, Alissa, Shi, Xu, Zheng, Shuning, Keyes, Michelle, Yu, Zhi, Gao, Yan, Farrell, Laurie, Shen, Dongxiao, Chen, Zsu-Zsu, Cruz, Daniel E, Sims, Mario, 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, Jain, Deepti, Yang, Qiong, Consortium, NHLBI Trans-Omics for Precision Medicine, Bouchard, Claude, Sarzynski, Mark A, Rich, Stephen S, Rotter, Jerome I, Wang, Thomas J, Wilson, James G, Clish, Clary B, Sarkar, Indra Neil, Natarajan, Pradeep, and Gerszten, Robert E

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Genetics, Medical Biochemistry and Metabolomics, Biotechnology, 2.1 Biological and endogenous factors, Humans, Animals, Mice, Proteomics, Metabolomics, Signal Transduction, Genome-Wide Association Study, Polymorphism, Single Nucleotide, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, GWAS, functional genomics, genome-wide association study, genomics, metabolomics, multi-omics, pathway discovery, proteomics, Endocrinology & Metabolism, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

Although many novel gene-metabolite and gene-protein associations have been identified using high-throughput biochemical profiling, systematic studies that leverage human genetics to illuminate causal relationships between circulating proteins and metabolites are lacking. Here, we performed protein-metabolite association studies in 3,626 plasma samples from three human cohorts. We detected 171,800 significant protein-metabolite pairwise correlations between 1,265 proteins and 365 metabolites, including established relationships in metabolic and signaling pathways such as the protein thyroxine-binding globulin and the metabolite thyroxine, as well as thousands of new findings. In Mendelian randomization (MR) analyses, we identified putative causal protein-to-metabolite associations. We experimentally validated top MR associations in proof-of-concept plasma metabolomics studies in three murine knockout strains of key protein regulators. These analyses identified previously unrecognized associations between bioactive proteins and metabolites in human plasma. We provide publicly available data to be leveraged for studies in human metabolism and disease.

Published
2023

4. Associations of Circulating ANGPTL3, C-Terminal Domain–Containing ANGPTL4, and ANGPTL3/8 and ANGPTL4/8 Complexes with LPL Activity, Diabetes, Inflammation, and Cardiovascular Mortality

Author

Silbernagel, Günther, Chen, Yan Q., Li, Hongxia, Lemen, Deven, Wen, Yi, Zhen, Eugene Y., Rief, Martin, Kleber, Marcus E., Delgado, Graciela, Sarzynski, Mark A., Qian, Yue-Wei, Schmidt, Boerge, Erbel, Raimund, Trampisch, Ulrike, Moissl, Angela P., Rudolf, Henrik, Schunkert, Heribert, Stang, Andreas, März, Winfried, Trampisch, Hans J., Scharnagl, Hubert, and Konrad, Robert J.

Published
2024
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5. Associations of an HDL apolipoproteomic index with cardiometabolic risk factors before and after exercise training in the HERITAGE Family Study

Author

Miranda Maravi, J. Sebastian, Leszczynski, Eric C., Schwartz, Charles S., Dev, Prasun K., Barber, Jacob L., Reasons, Riley J., Pearce, Ryan W., McPhaul, Michael J., Konrad, Robert J., Robbins, Jeremy M., Gerszten, Robert E., Collier, Timothy S., Bouchard, Claude, Rohatgi, Anand, and Sarzynski, Mark A.

Published
2024
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6. Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease

Author

Katz, Daniel H, Tahir, Usman A, Bick, Alexander G, Pampana, Akhil, Ngo, Debby, Benson, Mark D, Yu, Zhi, Robbins, Jeremy M, Chen, Zsu-Zsu, Cruz, Daniel E, Deng, Shuliang, Farrell, Laurie, Sinha, Sumita, Schmaier, Alec A, Shen, Dongxiao, Gao, Yan, Hall, Michael E, Correa, Adolfo, Tracy, Russell P, Durda, Peter, Taylor, Kent D, Liu, Yongmei, Johnson, W Craig, Guo, Xiuqing, Yao, Jie, Ida Chen, Yii-Der, Manichaikul, Ani W, Jain, Deepti, Bouchard, Claude, Sarzynski, Mark A, Rich, Stephen S, Rotter, Jerome I, Wang, Thomas J, Wilson, James G, Natarajan, Pradeep, Gerszten, Robert E, 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, 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, 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, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, and Chavan, Sameer

Subjects
Epidemiology, Health Sciences, Genetics, Minority Health, Cardiovascular, Biotechnology, Heart Disease, Prevention, Human Genome, 2.1 Biological and endogenous factors, Good Health and Well Being, Adult, Black People, Cardiovascular Diseases, Female, Genome-Wide Association Study, Humans, Male, Proteome, cardiovascular disease, genetics, proteomics, race and ethnicity, National Heart, Lung, and Blood Institute TOPMed (Trans-Omics for Precision Medicine) Consortium†, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundPlasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants.MethodsProteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics).ResultsWe identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10-11. These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P=3.27×10-30) and MMP-3 (β=-0.60±0.05, P=1.67×10-32), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P=1.34×10-17) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure.ConclusionsTaken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Published
2022

7. Metabolome-Wide Associations of Gestational Weight Gain in Pregnant Women with Overweight and Obesity

Author

Dai, Jin, Boghossian, Nansi S, Sarzynski, Mark A, Luo, Feng, Sun, Xiaoqian, Li, Jian, Fiehn, Oliver, Liu, Jihong, and Chen, Liwei

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Prevention, Clinical Research, Obesity, Good Health and Well Being, biomarkers, gestational weight gain, metabolomics, pregnancy, obesity, overweight, Analytical Chemistry, Biochemistry and Cell Biology, Clinical Sciences, Biochemistry and cell biology, Medical biochemistry and metabolomics, Analytical chemistry
Abstract

Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. This metabolome-wide association study aimed to identify metabolomic markers for GWG. This longitudinal study included 39 Black and White pregnant women with a prepregnancy body mass index (BMI) of ≥ 25 kg/m2. Untargeted metabolomic profiling was performed using fasting plasma samples collected at baseline (mean: 12.1 weeks) and 32 weeks of gestation. The associations of metabolites at each time point and changes between the two time points with GWG were examined by linear and least absolute shrinkage and selection operator (LASSO) regression analyses. Pearson correlations between the identified metabolites and cardiometabolic biomarkers were examined. Of the 769 annotated metabolites, 88 metabolites at 32 weeks were individually associated with GWG, with four (phosphatidylcholine (PC) 34:4, triacylglycerol (TAG) 52:6, arachidonic acid, isoleucine) jointly associated with GWG (area under the receiver operating characteristic curve (AUC) for excessive GWG: 0.80, 95% CI: 0.67, 0.93). No correlations were observed between the 88 metabolites and insulin, C-peptide, and high-sensitivity C-reactive protein at 32 weeks. Twelve metabolites at baseline (AUC for excessive GWG: 0.80, 95% CI: 0.62, 0.99) and three metabolite changes (AUC for excessive GWG: 0.73, 95% CI: 0.44, 1.00) were jointly associated with GWG. We identified novel metabolites in the first and third trimesters associated with GWG, which may shed light on the pathophysiology of GWG.

Published
2022

8. Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals

Author

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, Bouchard, Claude, Sarzynski, Mark A, Rich, Stephen S, Rotter, Jerome I, Wang, Thomas J, Wilson, James G, Clish, Clary B, Natarajan, Pradeep, and Gerszten, Robert E

Subjects
Analytical Chemistry, Biological Sciences, Biomedical and Clinical Sciences, Chemical Sciences, Genetics, Medical Biochemistry and Metabolomics, Minority Health, Rare Diseases, Health Disparities, Human Genome, 2.1 Biological and endogenous factors, Cardiovascular, Good Health and Well Being, Black People, Cardiovascular Diseases, Genome-Wide Association Study, Humans, Metabolome, Metabolomics, Tandem Mass Spectrometry, NHLBI Trans-Omics for Precision Medicine 1 Consortium
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.

Published
2022

14. A 12-Week Randomized Intervention Comparing the Healthy US, Mediterranean, and Vegetarian Dietary Patterns of the US Dietary Guidelines for Changes in Body Weight, Hemoglobin A1c, Blood Pressure, and Dietary Quality among African American Adults

Author

Turner-McGrievy, Gabrielle M., Wilson, Mary J., Carswell, Jessica, Okpara, Nkechi, Aydin, Halide, Bailey, Shiba, Davey, Marty, Hutto, Brent, Wilcox, Sara, Friedman, Daniela B., Sarzynski, Mark A., and Liese, Angela D.

Published
2023
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15. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J., Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C., Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S., Bartz, Traci M., Bentley, Amy R., Bielak, Lawrence F., Chong, Mike, Chu, Audrey Y., Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D., Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F., Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M., Haller, Toomas, Hartwig, Fernando P., Hillis, David A., Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U., Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A., Karlsson, Robert, Kerr, Kathleen F., Kim, Boram, Koolhaas, Chantal M., Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A., Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R., Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C., Rivera, Natalia V., Robiou-du-Pont, Sebastien, Schraut, Katharina E., Schulz, Christina-Alexandra, Stringham, Heather M., Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J., Vanmunster, Mathias, van Rooij, Frank J. A., van Vliet-Ostaptchouk, Jana V., Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N., Baumeister, Sebastian E., Beilby, John, Blangero, John, Boomsma, Dorret I., Brage, Soren, Braund, Peter S., Brody, Jennifer A., Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W., Collins, Francis S., Cupples, L. Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D., Fernandez-Rhodes, Lindsay, Fohner, Alison E., Franco, Oscar H., Galesloot, Tessel E., Gordon, Scott D., Grarup, Niels, Hartman, Catharina A., Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K., Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P., Kuusisto, Johanna, Launer, Lenore J., Li, Aihua, Linneberg, Allan, Luan, Jian’an, Vidal, Pedro Marques, Medland, Sarah E., Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P., Nolte, Ilja M., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Power, Christine, Raitakari, Olli T., Reedik, Mägi, Reiner, Alex P., Ridker, Paul M., Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A., Scott, Laura J., Scott, Robert A., Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V., Smith, Jennifer A., Sonestedt, Emily, Strøm, Marin, Tai, E. Shyong, Teo, Koon K., Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G., Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L., Yuan, Jian Min, Zillikens, M. Carola, Zonderman, Alan B., Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C., Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I., Smith, George Davey, de Geus, Eco J. C., Deldicque, Louise, Dörr, Marcus, Evans, Michele K., Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Jr, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L., Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W. Craig, Kardia, Sharon L. R., Kiemeney, Lambertus A., Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K. E., Martin, Nicholas G., Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E., Ohlsson, Claes, Oldehinkel, Albertine J., Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W. J. H., Pers, Tune H., Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N., Samani, Nilesh J., Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I. A., Spector, Tim D., Timpson, Nicholas J., van Dam, Rob M., van der Velde, Nathalie, van Duijn, Cornelia M., Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J., Weir, David R., Wichmann, Heinz-Erich, Wilson, James F., Hevener, Andrea L., Krook, Anna, Zierath, Juleen R., Thomis, Martine A. I., Loos, Ruth J. F., and Hoed, Marcel den

Published
2022
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16. Plasma protein patterns as comprehensive indicators of health

Author

Williams, Stephen A, Kivimaki, Mika, Langenberg, Claudia, Hingorani, Aroon D, Casas, JP, Bouchard, Claude, Jonasson, Christian, Sarzynski, Mark A, Shipley, Martin J, Alexander, Leigh, Ash, Jessica, Bauer, Tim, Chadwick, Jessica, Datta, Gargi, DeLisle, Robert Kirk, Hagar, Yolanda, Hinterberg, Michael, Ostroff, Rachel, Weiss, Sophie, Ganz, Peter, and Wareham, Nicholas J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Nutrition, Behavioral and Social Science, Obesity, Prevention, Heart Disease, Cardiovascular, Generic health relevance, Metabolic and endocrine, Good Health and Well Being, Adipose Tissue, Blood Proteins, Body Composition, Exercise, Female, Humans, Intra-Abdominal Fat, Life Style, Liver, Male, Precision Medicine, Risk Factors, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Proteins are effector molecules that mediate the functions of genes1,2 and modulate comorbidities3-10, behaviors and drug treatments11. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning12-16 coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.

Published
2019

17. Associations of Circulating ANGPTL3, C-Terminal Domain–Containing ANGPTL4, and ANGPTL3/8 and ANGPTL4/8 Complexes with LPL Activity, Diabetes, Inflammation, and Cardiovascular Mortality.

Author

Silbernagel, Günther, Chen, Yan Q., Li, Hongxia, Lemen, Deven, Wen, Yi, Zhen, Eugene Y., Rief, Martin, Kleber, Marcus E., Delgado, Graciela E., Sarzynski, Mark A., Qian, Yue-Wei, Schmidt, Boerge, Erbel, Raimund, Trampisch, Ulrike S., Moissl, Angela P., Rudolf, Henrik, Schunkert, Heribert, Stang, Andreas, März, Winfried, and Trampisch, Hans J.

Published
2025
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24. Abstract 13308: Complementary Investigations of Plasma Proteomics Identify Novel Protein Associations With Incident Diabetes and Glucose Metabolism

Author

Mi, Michael Y, Cronje, Helene T, Austin, Thomas R, Biggs, Mary L, Siscovick, David S, Lemaitre, Rozenn N, Psaty, Bruce M, Tracy, Russell P, Djousse, Luc, Kizer, Jorge R, IX, Joachim H, Sotoodehnia, Nona, Rao, Prashant, Robbins, Jeremy M, Barber, Jacob L, Sarzynski, Mark A, Clish, Clary, Bouchard, Claude, Mukamal, Ken J, Jensen, Majken K, and Gerszten, Robert E

Published
2022
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26. Human plasma proteomic profiles indicative of cardiorespiratory fitness

Author

Robbins, Jeremy M., Peterson, Bennet, Schranner, Daniela, Tahir, Usman A., Rienmüller, Theresa, Deng, Shuliang, Keyes, Michelle J., Katz, Daniel H., Beltran, Pierre M. Jean, Barber, Jacob L., Baumgartner, Christian, Carr, Steven A., Ghosh, Sujoy, Shen, Changyu, Jennings, Lori L., Ross, Robert, Sarzynski, Mark A., Bouchard, Claude, and Gerszten, Robert E.

Published
2021
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27. Effects of Weight Loss and Weight Maintenance on Lipoprotein Insulin Resistance Scores in Adults with Overweight and Obesity.

Author

Grammer, Emily E., McGee, Joshua E., Bartlett, Allison N., Brown, Taylor T., Clunan, Marie C., Huff, Anna C., Osborne, Briceida G., Matarese, Laura E., Pories, Walter J., Houmard, Joseph A., Carels, Robert A., Sarzynski, Mark A., and Swift, Damon L.

Abstract

Background: An elevated lipoprotein insulin resistance (LP-IR) score corresponds to insulin resistance in adults with overweight and obesity, yet data are lacking regarding the impact of exercise interventions on LP-IR. The purpose of this secondary analysis was to evaluate the effects of a weight loss and weight maintenance intervention on LP-IR score in adults with overweight and obesity. Methods: Thirty sedentary adults with overweight and obesity completed a 10-week OPTIFAST® weight loss program with supervised aerobic exercise to achieve clinical weight loss (CWL) (≥7% from baseline). Aerobic exercise volume increased weekly until 700 MET min/week was reached. Participants who reached CWL were randomized to groups at volumes at either physical activity (PA-REC) or weight maintenance (WM-REC) recommendations (weeks 11–28). Plasma blood samples were analyzed via nuclear magnetic resonance spectroscopy at baseline, after weight loss (week 10), and following weight maintenance (week 28). Results: Following the weight loss phase, on average, participants significantly (p < 0.001) reduced LP-IR score (−12.1 ± 13.5), body weight (−8.9 ± 2.7%), and waist circumference (−7.7 ± 4.1 cm). During the weight maintenance phase, there were no changes in LP-IR score between exercise groups (PA-REC: 4.1 ± 13.6; WM-REC: −2.0 ± 11.2; P = 0.7). The PA-REC group had improvements in LP-IR score from baseline (49.8 ± 24.6 to 36.6 ± 27.6, P < 0.001), yet there were no within-group changes during the weight maintenance phase (P > 0.05). Conclusion: LP-IR score improved during weight loss in adults with overweight and obesity and were sustained during the weight maintenance phase in the PA-REC group. Aerobic exercise at least at minimum guidelines following CWL can preserve LP-IR score improvements and may indicate a reduced T2DM risk in adults with overweight and obesity. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights into Cardiovascular Disease

Author

Katz, Daniel H., Tahir, Usman A., Bick, Alexander G., Pampana, Akhil, Ngo, Debby, Benson, Mark D., Yu, Zhi, Robbins, Jeremy M., Chen, Zsu-Zsu, Cruz, Daniel E., Deng, Shuliang, Farrell, Laurie, Sinha, Sumita, Schmaier, Alec A., Shen, Dongxiao, Gao, Yan, Hall, Michael E., Correa, Adolfo, Tracy, Russell P., Durda, Peter, Taylor, Kent D., Liu, Yongmei, Johnson, W. Craig, Guo, Xiuqing, Yao, Jie, Ida Chen, Yii-Der, Manichaikul, Ani W., Jain, Deepti, Bouchard, Claude, Sarzynski, Mark A., Rich, Stephen S., Rotter, Jerome I., Wang, Thomas J., Wilson, James G., Natarajan, Pradeep, and Gerszten, Robert E.

Published
2021
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31. The HERITAGE Family Study: A Review of the Effects of Exercise Training on Cardiometabolic Health, with Insights into Molecular Transducers

Author

SARZYNSKI, MARK A., RICE, TREVA K., DESPRÉS, JEAN-PIERRE, PÉRUSSE, LOUIS, TREMBLAY, ANGELO, STANFORTH, PHILIP R., TCHERNOF, ANDRÉ, BARBER, JACOB L., FALCIANI, FRANCESCO, CLISH, CLARY, ROBBINS, JEREMY M., GHOSH, SUJOY, GERSZTEN, ROBERT E., LEON, ARTHUR S., SKINNER, JAMES S., RAO, D. C., and BOUCHARD, CLAUDE

Published
2022
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34. Plasma Proteomics of Exercise Blood Pressure and Incident Hypertension

Author

Rao, Prashant, Keyes, Michelle. J., Mi, Michael Y., Barber, Jacob L., Tahir, Usman A., Deng, Shuliang, Clish, Clary B., Shen, Dongxiao, Farrell, Laurie. A., Wilson, James G., Gao, Yan, Yimer, Wondwosen K., Ekunwe, Lynette, Hall, Michael E., Muntner, Paul M., Guo, Xiuqing, Taylor, Kent D., Tracy, Russell P., Rich, Stephen S., Rotter, Jerome I., Xanthakis, Vanessa, Vasan, Ramachandran S., Bouchard, Claude, Sarzynski, Mark A., Gerszten, Robert E., and Robbins, Jeremy M.

Abstract

IMPORTANCE: Blood pressure response during acute exercise (exercise blood pressure [EBP]) is associated with the future risk of hypertension and cardiovascular disease (CVD). Biochemical characterization of EBP could inform disease biology and identify novel biomarkers of future hypertension. OBJECTIVE: To identify protein markers associated with EBP and test their association with incident hypertension. DESIGN, SETTING, AND PARTICIPANTS: This study assayed 4977 plasma proteins in 681 healthy participants (from 763 assessed) of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE; data collection from January 1993 to December 1997 and plasma proteomics from January 2019 to January 2020) Family Study at rest who underwent 2 cardiopulmonary exercise tests. Individuals were free of CVD at the time of recruitment. Individuals with resting SBP ≥160 mm Hg or DBP ≥100 mm Hg or taking antihypertensive drug therapy were excluded from the study. The association between resting plasma protein levels to both resting BP and EBP was evaluated. Proteins associated with EBP were analyzed for their association with incident hypertension in the Framingham Heart Study (FHS; n = 1177) and validated in the Jackson Heart Study (JHS; n = 772) and Multi-Ethnic Study of Atherosclerosis (MESA; n = 1367). Proteins associated with incident hypertension were tested for putative causal links in approximately 700 000 individuals using cis-protein quantitative loci mendelian randomization (cis-MR). Data were analyzed from January 2023 to January 2024. EXPOSURES: Plasma proteins. MAIN OUTCOMES AND MEASURES: EBP was defined as the BP response during a fixed workload (50 W) on a cycle ergometer. Hypertension was defined as BP ≥140/90 mm Hg or taking antihypertensive medication. RESULTS: Among the 681 participants in the HERITAGE Family Study, the mean (SD) age was 34 (13) years; 366 participants (54%) were female; 238 (35%) were self-reported Black and 443 (65%) were self-reported White. Proteomic profiling of EBP revealed 34 proteins that would not have otherwise been identified through profiling of resting BP alone. Transforming growth factor β receptor 3 (TGFBR3) and prostaglandin D2 synthase (PTGDS) had the strongest association with exercise systolic BP (SBP) and diastolic BP (DBP), respectively (TGFBR3: exercise SBP, β estimate, −3.39; 95% CI, −4.79 to −2.00; P = 2.33 × 10−6; PTGDS: exercise DBP β estimate, −2.50; 95% CI, −3.29 to −1.70; P = 1.18 × 10−9). In fully adjusted models, TGFBR3 was inversely associated with incident hypertension in FHS, JHS, and MESA (hazard ratio [HR]: FHS, 0.86; 95% CI, 0.75-0.97; P = .01; JHS, 0.87; 95% CI, 0.77-0.97; P = .02; MESA, 0.84; 95% CI, 0.71-0.98; P = .03; pooled cohort, 0.86; 95% CI, 0.79-0.92; P = 6 × 10−5). Using cis-MR, genetically predicted levels of TGFBR3 were associated with SBP, hypertension, and CVD events (SBP: β, −0.38; 95% CI, −0.64 to −0.11; P = .006; hypertension: odds ratio [OR], 0.99; 95% CI, 0.98-0.99; P &lt; .001; heart failure with hypertension: OR, 0.86; 95% CI, 0.77-0.97; P = .01; CVD: OR, 0.84; 95% CI, 0.77-0.92; P = 8 × 10−5; cerebrovascular events: OR, 0.77; 95% CI, 0.70-0.85; P = 5 × 10−7). CONCLUSIONS AND RELEVANCE: Plasma proteomic profiling of EBP identified a novel protein, TGFBR3, which may protect against elevated BP and long-term CVD outcomes.

Published
2024
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39. Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability

Author

Hota, Monalisa, primary, Barber, Jacob L, additional, Ruiz-Ramie, Jonathan J., additional, Schwartz, Charles S., additional, Lam, Do Thuy Uyen Ha, additional, Rao, Prashant, additional, Mi, Michael Y., additional, Katz, Daniel H., additional, Robbins, Jeremy, additional, Clish, Clary B., additional, Gerszten, Robert E, additional, Sarzynski, Mark A., additional, Ghosh, Sujoy, additional, and Bouchard, Claude, additional

Published
2023
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40. Effects Of Weight Loss And Maintenance On Apolipoprotein B In Overweight And Obese Adults

Author

Grammer, Emily E., primary, McGee, Joshua E., additional, Brown, Taylor T., additional, Clunan, Marie C., additional, Huff, Anna C., additional, Osborne, Briceida G., additional, Matarese, Laura E., additional, Pories, Walter J., additional, Houmard, Joseph A., additional, Carels, Robert A., additional, Sarzynski, Mark A., additional, and Swift, Damon L., additional

Published
2023
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41. Effects Of Weight Loss And Weight Maintenance On Inflammation In Overweight And Obese Adults

Author

Stahl, Macy E., primary, Grammer, Emily E., additional, McGee, Joshua E., additional, Brown, Taylor T., additional, Clunan, Marie C., additional, Huff, Anna C., additional, Osborne, Briceida G., additional, Matarese, Laura E., additional, Pories, Walter J., additional, Houmard, Joseph A., additional, Carels, Robert A., additional, Sarzynski, Mark A., additional, and Swift, Damon L., additional

Published
2023
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43. The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

Author

Clarke, Kim, Ricciardi, Sara, Pearson, Tim, Bharudin, Izwan, Davidsen, Peter K., Bonomo, Michela, Brina, Daniela, Scagliola, Alessandra, Simpson, Deborah M., Beynon, Robert J., Khanim, Farhat, Ankers, John, Sarzynski, Mark A., Ghosh, Sujoy, Pisconti, Addolorata, Rozman, Jan, Hrabe de Angelis, Martin, Bunce, Chris, Stewart, Claire, Egginton, Stuart, Caddick, Mark, Jackson, Malcolm, Bouchard, Claude, Biffo, Stefano, and Falciani, Francesco

Published
2017
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