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1. 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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2. 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, Aging, Heart Disease - Coronary Heart Disease, Human Genome, Genetics, Prevention, Cardiovascular, Heart Disease, Biotechnology, Aetiology, 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

3. 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

4. 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, Clinical Research, Orphan Drug, Biotechnology, Human Genome, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, 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

6. 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, 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.

Published
2023
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7. 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

15. 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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17. 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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18. 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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20. 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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21. 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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22. 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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25. Inverse association between apolipoprotein C-II and cardiovascular mortality: role of lipoprotein lipase activity modulation

Author

Silbernagel, Günther, primary, Chen, Yan Q, additional, Rief, Martin, additional, Kleber, Marcus E, additional, Hoffmann, Michael M, additional, Stojakovic, Tatjana, additional, Stang, Andreas, additional, Sarzynski, Mark A, additional, Bouchard, Claude, additional, März, Winfried, additional, Qian, Yue-Wei, additional, Scharnagl, Hubert, additional, and Konrad, Robert J, additional

Published
2023
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26. Abstract 679: HDL Apolipoproteomic Score, Cardiometabolic Risk, And Exercise Training

Author

Miranda Maravi, Juan S, primary, Schwartz, Charles S, additional, Dev, Prasun K, additional, Barber, Jacob L, additional, Reasons, Riley J, additional, Pearce, Ryan W, additional, Mcphaul, Michael J, additional, Gerszten, Robert E, additional, Rohatgi, Anand, additional, Bouchard, Claude, additional, Collier, Timothy S, additional, and Sarzynski, Mark A, additional

Published
2023
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29. Plasma proteomic changes in response to exercise training are associated with cardiorespiratory fitness adaptations

Author

Robbins, Jeremy M., primary, Rao, Prashant, additional, Deng, Shuliang, additional, Keyes, Michelle J., additional, Tahir, Usman A., additional, Katz, Daniel H., additional, Beltran, Pierre M. Jean, additional, Marchildon, François, additional, Barber, Jacob L., additional, Peterson, Bennet, additional, Gao, Yan, additional, Correa, Adolfo, additional, Wilson, James G., additional, Smith, J. Gustav, additional, Cohen, Paul, additional, Ross, Robert, additional, Bouchard, Claude, additional, Sarzynski, Mark A., additional, and Gerszten, Robert E., additional

Published
2023
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35. Abstract P201: Plasma Proteomic Signatures of Angptl3/8 and 4/8 Before and After Exercise Training

Author

Miranda-Maravi, Sebastian, primary, Hoffman, William G, additional, Dev, Prasun K, additional, Barber, Jacob L, additional, Schwartz, Charles S, additional, Clarkson, William A, additional, Robbins, Jeremy M, additional, Rao, Prashant, additional, Mi, Michael, additional, Ghosh, Sujoy, additional, Clish, Clary, additional, Silbernagel, Gunther, additional, Chen, Yan Q, additional, Konrad, Robert J, additional, Bouchard, Claude, additional, Gerszten, Robert E, additional, and Sarzynski, Mark A, additional

Published
2023
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36. Abstract P205: Association of Angptl3/8 and 4/8 With Plasma Metabolites Before and After Exercise Training

Author

Dev, Prasun K, primary, Miranda-Maravi, Sebastian, additional, Hoffman, William, additional, Barber, Jacob L, additional, Schwartz, Charles S, additional, Clarkson, William A, additional, Robbins, Jeremy M, additional, Rao, Prashant, additional, Mi, Michael, additional, Ghosh, Sujoy, additional, Clish, Clary, additional, Silbernagel, Gunther, additional, Chen, Yan Q, additional, Konrad, Robert J, additional, Bouchard, Claude, additional, Gerszten, Robert E, additional, and Sarzynski, Mark A, additional

Published
2023
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37. Plasma Proteomic Risk Markers of Incident Type 2 Diabetes Reflect Physiologically Distinct Components of Glucose-Insulin Homeostasis

Author

Cronjé, Héléne T., primary, Mi, Michael Y., additional, Austin, Thomas R., additional, Biggs, Mary L., additional, Siscovick, David S., additional, Lemaitre, Rozenn N., additional, Psaty, Bruce M., additional, Tracy, Russell P., additional, Djoussé, Luc, additional, Kizer, Jorge R., additional, Ix, Joachim H., additional, Rao, Prashant, additional, Robbins, Jeremy M., additional, Barber, Jacob L., additional, Sarzynski, Mark A., additional, Clish, Clary B., additional, Bouchard, Claude, additional, Mukamal, Kenneth J., additional, Gerszten, Robert E., additional, and Jensen, Majken K., additional

Published
2023
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38. 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., primary, Wilson, Mary J., additional, Carswell, Jessica, additional, Okpara, Nkechi, additional, Aydin, Halide, additional, Bailey, Shiba, additional, Davey, Marty, additional, Hutto, Brent, additional, Wilcox, Sara, additional, Friedman, Daniela B., additional, Sarzynski, Mark A., additional, and Liese, Angela D., additional

Published
2023
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39. PWC150_Supplemental Tables 1-13.xlsx

Author

Sarzynski, Sarzynski, Mark A., Bouchard, Claude, and Ghosh, Sujoy

Abstract

Supplemental tables for PWC150 manuscript titled "Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability" for Physiological Genomics

Published
2023
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44. 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, Søren Karl, 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, 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, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Swertz, Morris, Wijmenga, Tjitske Nienke, van der Harst, Pim, Navis, Gerjan, Rots, Marianne, Wolffenbuttel, Bruce H. R., 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., Hoed, Marcel den, Epidemiology, Internal Medicine, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hyppönen, Elina, den Hoed, Marcel, Lifelines Cohort Study, Alizadeh, B.Z., Boezen, H.M., Franke, L., Swertz, M., Wijmenga, C., van der Harst, P., Navis, G., Rots, M., Wolffenbuttel, BHR, Wang, Zhe [0000-0002-8046-4969], Emmerich, Andrew [0000-0002-0908-9924], Pillon, Nicolas J [0000-0003-1107-9490], Moore, Tim [0000-0003-4250-3370], Ameur, Adam [0000-0001-6085-6749], Bis, Joshua C [0000-0002-3409-1110], Boehnke, Michael [0000-0002-6442-7754], Bouchard, Claude [0000-0002-0048-491X], Chasman, Daniel I [0000-0003-3357-0862], Smith, George Davey [0000-0002-1407-8314], de Geus, Eco JC [0000-0001-6022-2666], Dörr, Marcus [0000-0001-7471-475X], Ferrucci, Luigi [0000-0002-6273-1613], Fornage, Myriam [0000-0003-0677-8158], Garland, Theodore [0000-0002-7916-3552], Gyllensten, Ulf [0000-0002-6316-3355], Hansen, Torben [0000-0001-8748-3831], Horta, Bernardo L [0000-0001-9843-412X], Hyppönen, Elina [0000-0003-3670-9399], Johnson, W Craig [0000-0002-3161-3753], Kiemeney, Lambertus A [0000-0002-2368-1326], Laakso, Markku [0000-0002-3394-7749], Langenberg, Claudia [0000-0002-5017-7344], Lehtimäki, Terho [0000-0002-2555-4427], Magnusson, Patrik KE [0000-0002-7315-7899], Martin, Nicholas G [0000-0003-4069-8020], Melbye, Mads [0000-0001-8264-6785], Metspalu, Andres [0000-0002-3718-796X], Meyre, David [0000-0003-4850-7444], North, Kari E [0000-0002-8903-0366], Ohlsson, Claes [0000-0002-9633-2805], Oldehinkel, Albertine J [0000-0003-3925-3913], Orho-Melander, Marju [0000-0002-3578-2503], Pare, Guillaume [0000-0002-6795-4760], Park, Taesung [0000-0002-8294-590X], Pedersen, Oluf [0000-0002-3321-3972], Pers, Tune H [0000-0003-0207-4831], Polasek, Ozren [0000-0002-5765-1862], Prokopenko, Inga [0000-0003-1624-7457], Rotimi, Charles N [0000-0001-5759-053X], Sim, Xueling [0000-0002-1233-7642], Snieder, Harold [0000-0003-1949-2298], Sørensen, Thorkild IA [0000-0003-4821-430X], Spector, Tim D [0000-0002-9795-0365], Timpson, Nicholas J [0000-0002-7141-9189], Voortman, Trudy [0000-0003-2830-6813], Waeber, Gérard [0000-0003-4193-788X], Wareham, Nicholas J [0000-0003-1422-2993], Weir, David R [0000-0002-1661-2402], Wilson, James F [0000-0001-5751-9178], Krook, Anna [0000-0002-0891-0258], Zierath, Juleen R [0000-0001-6891-7497], Thomis, Martine AI [0000-0001-9093-2191], Loos, Ruth JF [0000-0002-8532-5087], Hoed, Marcel den [0000-0001-8081-428X], Apollo - University of Cambridge Repository, Center for Liver, Digestive and Metabolic Diseases (CLDM), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Geriatrics, AMS - Ageing & Vitality, APH - Aging & Later Life, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, and AMS - Sports

Subjects
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 631/208/205/2138, 610 Medicine & health, heritability, Actinin/genetics, Cross-Sectional Studies, Exercise/physiology, Genome-Wide Association Study, Humans, Leisure Activities, Sedentary Behavior, apolipoprotein-e genotype, Lifelines Cohort Study, 360 Social problems & social services, 692/308/575, Genetics, Actinin, Exercise, Medicinsk genetik, exercise, APOLIPOPROTEIN-E GENOTYPE, LD SCORE REGRESSION, GENE-EXPRESSION, EXERCISE, COMPLEX, PERFORMANCE, GWAS, HERITABILITY, MORTALITY, FITNESS, 360 Soziale Probleme, Sozialdienste, 692/308/2056, article, gwas, gene-expression, mortality, 3142 Public health care science, environmental and occupational health, fitness, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], LD score regression, 3111 Biomedicine, 610 Medizin und Gesundheit, Medical Genetics, complex, performance
Abstract

Funder: Kjell och Märta Beijers Stiftelse (Kjell and Marta Beijer Foundation); doi: https://doi.org/10.13039/501100006353, Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022
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47. EXERCISE TRAINING SLOWS DOWN PROTEOMIC AGE ACCELERATION IN MIDDLE-AGED TO OLDER ADULTS- HERITAGE FAMILY STUDY

Author

Dev, Prasun K., primary, Barbar, Jacob L., additional, Cai, Guoshuai, additional, Robbins, Jeremy M., additional, Rao, Prashant, additional, Mi, Michael, additional, Ghosh, Sujoy, additional, Clish, Clary, additional, Katz, Daniel H., additional, Gerszten, Robert E., additional, Bouchard, Claude, additional, and Sarzynski, Mark A., additional

Published
2022
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49. Associations Between Changes In Plasma Proteins And Body Composition Traits In Response To Endurance Training

Author

Clarkson, William A., primary, Barber, Jacob L., additional, Robbins, Jeremy M., additional, Rao, Prashant, additional, Mi, Michael, additional, Dev, Prasun K., additional, Ghosh, Sujoy, additional, Clish, Clary, additional, Katz, Daniel H., additional, Gerszten, Robert E., additional, Bouchard, Claude, additional, and Sarzynski, Mark A., additional

Published
2022
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