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1. Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes

Author

McKay, S., Haymond, M., Anderson, B., Bush, C., Gunn, S., Holden, H., Jones, S.M., Jeha, G., McGirk, S., Thamotharan, S., Cuttler, L., Abrams, E., Casey, T., Dahms, W., Ievers-Landis, C., Kaminski, B., Koontz, M., MacLeish, S., McGuigan, P., Narasimhan, S., Geffner, M., Barraza, V., Chang, N., Conrad, B., Dreimane, D., Estrada, S., Fisher, L., Fleury-Milfort, E., Hernandez, S., Hollen, B., Kaufman, F., Law, E., Mansilla, V., Miller, D., Muñoz, C., Ortiz, R., Ward, A., Wexler, K., Xu, Y.K., Yasuda, P., Berkowitz, R., Boyd, S., Johnson, B., Kaplan, J., Keating, C., Lassiter, C., Lipman, T., McGinley, G., McKnight, H., Schwartzman, B., Willi, S., Arslanian, S., Foster, S., Galvin, B., Hannon, T., Kriska, A., Marcus, M., Songer, T., Venditti, E., Goland, R., Gallagher, D., Kringas, P., Leibel, N., Ng, D., Ovalles, M., Seidman, D., Laffel, L., Goebel-Fabbri, A., Hall, M., Higgins, L., Keady, J., Malloy, M., Milaszewski, K., Rasbach, L., Nathan, D.M., Angelescu, A., Bissett, L., Ciccarelli, C., Delahanty, L., Goldman, V., Hardy, O., Larkin, M., Levitsky, L., McEachern, R., Norman, D., Nwosu, D., Park-Bennett, S., Richards, D., Sherry, N., Steiner, B., Tollefsen, S., Carnes, S., Dempsher, D., Flomo, D., Whelan, T., Wolff, B., Bowerman, D., Bristol, S., Bulger, J., Hartsig, J., Izquierdo, R., Kearns, J., Saletsky, R., Trief, P., Zeitler, P., Abramson, N., Bradhurst, A., Celona-Jacobs, N., Higgins, J., Kelsey, M., Klingensmith, G., Witten, T., Copeland, K., Boss, E., Brown, R., Chadwick, J., Chalmers, L., Chernausek, S., Hebensperger, A., Macha, C., Newgent, R., Nordyke, A., Olson, D., Poulsen, T., Pratt, L., Preske, J., Schanuel, J., Sternlof, S., Lynch, J., Amodei, N., Barajas, R., Cody, C., Hale, D., Hernandez, J., Ibarra, C., Morales, E., Rivera, S., Rupert, G., Wauters, A., White, N., Arbeláez, A., Jones, J., Jones, T., Sadler, M., Tanner, M., Timpson, A., Welch, R., Caprio, S., Grey, M., Guandalini, C., Lavietes, S., Rose, P., Syme, A., Tamborlane, W., Hirst, K., Edelstein, S., Feit, P., Grover, N., Long, C., Pyle, L., Linder, B., Harting, J., Shepherd, J., Fan, B., Marquez, L., Sherman, M., Wang, J., Nichols, M., Mayer-Davis, E., Liu, Y., Lima, J., Puccella, J., Ricketts, E., Danis, R., Domalpally, A., Goulding, A., Neill, S., Vargo, P., Wilfley, D., Aldrich-Rasche, D., Franklin, K., Massmann, C., O'Brien, D., Patterson, J., Tibbs, T., Van Buren, D., Palmert, M., Ratner, R., Dremaine, D., Silverstein, J., Levitt Katz, Lorraine E., Bacha, Fida, Gidding, Samuel S., Weinstock, Ruth S., El ghormli, Laure, Libman, Ingrid, Nadeau, Kristen J., Porter, Kristin, and Marcovina, Santica

Published
2018
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2. Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial

Author

McKay, S., Haymond, M., Anderson, B., Bush, C., Gunn, S., Holden, H., Jones, S.M., Jeha, G., McGirk, S., Thamotharan, S., Cuttler, L., Abrams, E., Casey, T., Dahms, W., Ievers-Landis, C., Kaminski, B., Koontz, M., MacLeish, S., McGuigan, P., Narasimhan, S., Geffner, M., Barraza, V., Chang, N., Conrad, B., Dreimane, D., Estrada, S., Fisher, L., Fleury-Milfort, E., Hernandez, S., Hollen, B., Kaufman, F., Law, E., Mansilla, V., Miller, D., Muñoz, C., Ortiz, R., Ward, A., Wexler, K., Xu, Y.K., Yasuda, P., Levitt Katz, L., Berkowitz, R., Boyd, S., Johnson, B., Kaplan, J., Keating, C., Lassiter, C., Lipman, T., McGinley, G., McKnight, H., Schwartzman, B., Willi, S., Arslanian, S., Bacha, F., Foster, S., Galvin, B., Hannon, T., Kriska, A., Libman, I., Marcus, M., Porter, K., Songer, T., Venditti, E., Goland, R., Gallagher, D., Kringas, P., Leibel, N., Ng, D., Ovalles, M., Seidman, D., Laffel, L., Goebel-Fabbri, A., Hall, M., Higgins, L., Keady, J., Malloy, M., Milaszewski, K., Rasbach, L., Nathan, D.M., Angelescu, A., Bissett, L., Ciccarelli, C., Delahanty, L., Goldman, V., Hardy, O., Larkin, M., Levitsky, L., McEachern, R., Norman, D., Nwosu, D., Park-Bennett, S., Richards, D., Sherry, N., Steiner, B., Tollefsen, S., Carnes, S., Dempsher, D., Flomo, D., Whelan, T., Wolff, B., Weinstock, R., Bowerman, D., Bristol, S., Bulger, J., Hartsig, J., Izquierdo, R., Kearns, J., Saletsky, R., Trief, P., Zeitler, P., Abramson, N., Bradhurst, A., Celona-Jacobs, N., Higgins, J., Kelsey, M., Klingensmith, G., Nadeau, K., Witten, T., Copeland, K., Boss, E., Brown, R., Chadwick, J., Chalmers, L., Chernausek, S., Hebensperger, A., Macha, C., Newgent, R., Nordyke, A., Olson, D., Poulsen, T., Pratt, L., Preske, J., Schanuel, J., Sternlof, S., Lynch, J., Amodei, N., Barajas, R., Cody, C., Hale, D., Hernandez, J., Ibarra, C., Morales, E., Rivera, S., Rupert, G., Wauters, A., White, N., Arbeláez, A., Jones, J., Jones, T., Sadler, M., Tanner, M., Timpson, A., Welch, R., Caprio, S., Grey, M., Guandalini, C., Lavietes, S., Rose, P., Syme, A., Tamborlane, W., Hirst, K., Edelstein, S., Feit, P., Grover, N., Long, C., Pyle, L., Linder, B., Marcovina, S.M., Harting, J., Shepherd, J., Fan, B., Marquez, L., Sherman, M., Wang, J., Nichols, M., Mayer-Davis, E., Liu, Y., Lima, J., Gidding, S., Puccella, J., Ricketts, E., Danis, R., Domalpally, A., Goulding, A., Neill, S., Vargo, P., Wilfley, D., Aldrich-Rasche, D., Franklin, K., Massmann, C., O’Brien, D., Patterson, J., Tibbs, T., Van Buren, D., Palmert, M., Ratner, R., Dremaine, D., Silverstein, J., Bjornstad, Petter, Nehus, Edward, El ghormli, Laure, Bacha, Fida, Libman, Ingrid M., McKay, Siripoom, Willi, Steven M., Laffel, Lori, Arslanian, Silva, and Nadeau, Kristen J.

Published
2018
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3. Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study

Author

McKay, S., Haymond, M., Anderson, B., Bush, C., Gunn, S., Holden, H., Jones, S.M., Jeha, G., McGirk, S., Thamotharan, S., Cuttler, L., Abrams, E., Casey, T., Dahms, W., Ievers-Landis, C., Kaminski, B., Koontz, M., MacLeish, S., McGuigan, P., Narasimhan, S., Geffner, M., Barraza, V., Chang, N., Conrad, B., Dreimane, D., Estrada, S., Fisher, L., Fleury-Milfort, E., Hernandez, S., Hollen, B., Kaufman, F., Law, E., Mansilla, V., Miller, D., Muñoz, C., Ortiz, R., Ward, A., Wexler, K., Xu, Y.K., Yasuda, P., Levitt Katz, L., Berkowitz, R., Boyd, S., Johnson, B., Kaplan, J., Keating, C., Lassiter, C., Lipman, T., McGinley, G., McKnight, H., Schwartzman, B., Willi, S., Arslanian, S., Bacha, F., Foster, S., Galvin, B., Hannon, T., Kriska, A., Libman, I., Marcus, M., Porter, K., Songer, T., Venditti, E., Goland, R., Gallagher, D., Kringas, P., Leibel, N., Ng, D., Ovalles, M., Seidman, D., Laffel, L., Goebel-Fabbri, A., Hall, M., Higgins, L., Keady, J., Malloy, M., Milaszewski, K., Rasbach, L., Nathan, D.M., Angelescu, A., Bissett, L., Ciccarelli, C., Delahanty, L., Goldman, V., Hardy, O., Larkin, M., Levitsky, L., McEachern, R., Norman, D., Nwosu, D., Park-Bennett, S., Richards, D., Sherry, N., Steiner, B., Tollefsen, S., Carnes, S., Dempsher, D., Flomo, D., Whelan, T., Wolff, B., Weinstock, R., Bowerman, D., Bristol, S., Bulger, J., Hartsig, J., Izquierdo, R., Kearns, J., Saletsky, R., Trief, P., Zeitler, P., Abramson, N., Bradhurst, A., Celona-Jacobs, N., Higgins, J., Kelsey, M., Klingensmith, G., Nadeau, K., Witten, T., Copeland, K., Boss, E., Brown, R., Chadwick, J., Chalmers, L., Chernausek, S., Hebensperger, A., Macha, C., Newgent, R., Nordyke, A., Olson, D., Poulsen, T., Pratt, L., Preske, J., Schanuel, J., Sternlof, S., Lynch, J., Amodei, N., Barajas, R., Cody, C., Hale, D., Hernandez, J., Ibarra, C., Morales, E., Rivera, S., Rupert, G., Wauters, A., White, N., Arbeláez, A., Jones, J., Jones, T., Sadler, M., Tanner, M., Timpson, A., Welch, R., Caprio, S., Grey, M., Guandalini, C., Lavietes, S., Rose, P., Syme, A., Tamborlane, W., Hirst, K., Edelstein, S., Feit, P., Grover, N., Long, C., Pyle, L., Linder, B., Marcovina, S.M., Harting, J., Shepherd, J., Fan, B., Marquez, L., Sherman, M., Wang, J., Nichols, M., Mayer-Davis, E., Liu, Y., Lima, J., Gidding, S., Puccella, J., Ricketts, E., Danis, R., Domalpally, A., Goulding, A., Neill, S., Vargo, P., Wilfley, D., Aldrich-Rasche, D., Franklin, K., Massmann, C., O'Brien, D., Patterson, J., Tibbs, T., Van Buren, D., Palmert, M., Ratner, R., Dremaine, D., Silverstein, J., Gidding, Samuel S., Bacha, Fida, Bjornstad, Petter, Levitt Katz, Lorraine E., Levitsky, Lynne L., Lynch, Jane, Tryggestad, Jeanie B., Weinstock, Ruth S., El ghormli, Laure, and Lima, Joao A.C.

Published
2018
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4. Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study

Author

Gidding, Samuel S., Bacha, Fida, Bjornstad, Petter, Katz, Lorraine E. Levitt, Levitsky, Lynne L., Lynch, Jane, Tryggestad, Jeanie B., Weinstock, Ruth S., El ghormli, Laure, Lima, Joao A.C., McKay, S., Haymond, M., Anderson, B., Bush, C., Gunn, S., Holden, H., Jones, S. M., Jeha, G., McGirk, S., Thamotharan, S., Cuttler, L., Abrams, E., Casey, T., Dahms, W., Ievers-Landis, C., Kaminski, B., Koontz, M., MacLeish, S., McGuigan, P., Narasimhan, S., Geffner, M., Barraza, V., Chang, N., Conrad, B., Dreimane, D., Estrada, S., Fisher, L., Fleury-Milfort, E., Hernandez, S., Hollen, B., Kaufman, F., Law, E., Mansilla, V., Miller, D., Muñoz, C., Ortiz, R., Ward, A., Wexler, K., Xu, Y. K., Yasuda, P., Katz, Levitt L., Berkowitz, R., Boyd, S., Johnson, B., Kaplan, J., Keating, C., Lassiter, C., Lipman, T., McGinley, G., McKnight, H., Schwartzman, B., Willi, S., Arslanian, S., Bacha, F., Foster, S., Galvin, B., Hannon, T., Kriska, A., Libman, I., Marcus, M., Porter, K., Songer, T., Venditti, E., Goland, R., Gallagher, D., Kringas, P., Leibel, N., Ng, D., Ovalles, M., Seidman, D., Laffel, L., Goebel-Fabbri, A., Hall, M., Higgins, L., Keady, J., Malloy, M., Milaszewski, K., Rasbach, L., Nathan, D. M., Angelescu, A., Bissett, L., Ciccarelli, C., Delahanty, L., Goldman, V., Hardy, O., Larkin, M., Levitsky, L., McEachern, R., Norman, D., Nwosu, D., Park-Bennett, S., Richards, D., Sherry, N., Steiner, B., Tollefsen, S., Carnes, S., Dempsher, D., Flomo, D., Whelan, T., Wolff, B., Weinstock, R., Bowerman, D., Bristol, S., Bulger, J., Hartsig, J., Izquierdo, R., Kearns, J., Saletsky, R., Trief, P., Zeitler, P., Abramson, N., Bradhurst, A., Celona-Jacobs, N., Higgins, J., Kelsey, M., Klingensmith, G., Nadeau, K., Witten, T., Copeland, K., Boss, E., Brown, R., Chadwick, J., Chalmers, L., Chernausek, S., Hebensperger, A., Macha, C., Newgent, R., Nordyke, A., Olson, D., Poulsen, T., Pratt, L., Preske, J., Schanuel, J., Sternlof, S., Lynch, J., Amodei, N., Barajas, R., Cody, C., Hale, D., Hernandez, J., Ibarra, C., Morales, E., Rivera, S., Rupert, G., Wauters, A., White, N., Arbeláez, A., Jones, J., Jones, T., Sadler, M., Tanner, M., Timpson, A., Welch, R., Caprio, S., Grey, M., Guandalini, C., Lavietes, S., Rose, P., Syme, A., Tamborlane, W., Hirst, K., Edelstein, S., Feit, P., Grover, N., Long, C., Pyle, L., Linder, B., Marcovina, S. M., Harting, J., Shepherd, J., Fan, B., Marquez, L., Sherman, M., Wang, J., Nichols, M., Mayer-Davis, E., Liu, Y., Lima, J., Gidding, S., Puccella, J., Ricketts, E., Danis, R., Domalpally, A., Goulding, A., Neill, S., Vargo, P., Wilfley, D., Aldrich-Rasche, D., Franklin, K., Massmann, C., O’Brien, D., Patterson, J., Tibbs, T., Van Buren, D., Palmert, M., Ratner, R., Dremaine, D., and Silverstein, J.

Published
2018
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7. Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes

Author

Levitt Katz, Lorraine E., primary, Bacha, Fida, additional, Gidding, Samuel S., additional, Weinstock, Ruth S., additional, El ghormli, Laure, additional, Libman, Ingrid, additional, Nadeau, Kristen J., additional, Porter, Kristin, additional, Marcovina, Santica, additional, McKay, S., additional, Haymond, M., additional, Anderson, B., additional, Bush, C., additional, Gunn, S., additional, Holden, H., additional, Jones, S.M., additional, Jeha, G., additional, McGirk, S., additional, Thamotharan, S., additional, Cuttler, L., additional, Abrams, E., additional, Casey, T., additional, Dahms, W., additional, Ievers-Landis, C., additional, Kaminski, B., additional, Koontz, M., additional, MacLeish, S., additional, McGuigan, P., additional, Narasimhan, S., additional, Geffner, M., additional, Barraza, V., additional, Chang, N., additional, Conrad, B., additional, Dreimane, D., additional, Estrada, S., additional, Fisher, L., additional, Fleury-Milfort, E., additional, Hernandez, S., additional, Hollen, B., additional, Kaufman, F., additional, Law, E., additional, Mansilla, V., additional, Miller, D., additional, Muñoz, C., additional, Ortiz, R., additional, Ward, A., additional, Wexler, K., additional, Xu, Y.K., additional, Yasuda, P., additional, Berkowitz, R., additional, Boyd, S., additional, Johnson, B., additional, Kaplan, J., additional, Keating, C., additional, Lassiter, C., additional, Lipman, T., additional, McGinley, G., additional, McKnight, H., additional, Schwartzman, B., additional, Willi, S., additional, Arslanian, S., additional, Foster, S., additional, Galvin, B., additional, Hannon, T., additional, Kriska, A., additional, Marcus, M., additional, Songer, T., additional, Venditti, E., additional, Goland, R., additional, Gallagher, D., additional, Kringas, P., additional, Leibel, N., additional, Ng, D., additional, Ovalles, M., additional, Seidman, D., additional, Laffel, L., additional, Goebel-Fabbri, A., additional, Hall, M., additional, Higgins, L., additional, Keady, J., additional, Malloy, M., additional, Milaszewski, K., additional, Rasbach, L., additional, Nathan, D.M., additional, Angelescu, A., additional, Bissett, L., additional, Ciccarelli, C., additional, Delahanty, L., additional, Goldman, V., additional, Hardy, O., additional, Larkin, M., additional, Levitsky, L., additional, McEachern, R., additional, Norman, D., additional, Nwosu, D., additional, Park-Bennett, S., additional, Richards, D., additional, Sherry, N., additional, Steiner, B., additional, Tollefsen, S., additional, Carnes, S., additional, Dempsher, D., additional, Flomo, D., additional, Whelan, T., additional, Wolff, B., additional, Bowerman, D., additional, Bristol, S., additional, Bulger, J., additional, Hartsig, J., additional, Izquierdo, R., additional, Kearns, J., additional, Saletsky, R., additional, Trief, P., additional, Zeitler, P., additional, Abramson, N., additional, Bradhurst, A., additional, Celona-Jacobs, N., additional, Higgins, J., additional, Kelsey, M., additional, Klingensmith, G., additional, Witten, T., additional, Copeland, K., additional, Boss, E., additional, Brown, R., additional, Chadwick, J., additional, Chalmers, L., additional, Chernausek, S., additional, Hebensperger, A., additional, Macha, C., additional, Newgent, R., additional, Nordyke, A., additional, Olson, D., additional, Poulsen, T., additional, Pratt, L., additional, Preske, J., additional, Schanuel, J., additional, Sternlof, S., additional, Lynch, J., additional, Amodei, N., additional, Barajas, R., additional, Cody, C., additional, Hale, D., additional, Hernandez, J., additional, Ibarra, C., additional, Morales, E., additional, Rivera, S., additional, Rupert, G., additional, Wauters, A., additional, White, N., additional, Arbeláez, A., additional, Jones, J., additional, Jones, T., additional, Sadler, M., additional, Tanner, M., additional, Timpson, A., additional, Welch, R., additional, Caprio, S., additional, Grey, M., additional, Guandalini, C., additional, Lavietes, S., additional, Rose, P., additional, Syme, A., additional, Tamborlane, W., additional, Hirst, K., additional, Edelstein, S., additional, Feit, P., additional, Grover, N., additional, Long, C., additional, Pyle, L., additional, Linder, B., additional, Harting, J., additional, Shepherd, J., additional, Fan, B., additional, Marquez, L., additional, Sherman, M., additional, Wang, J., additional, Nichols, M., additional, Mayer-Davis, E., additional, Liu, Y., additional, Lima, J., additional, Puccella, J., additional, Ricketts, E., additional, Danis, R., additional, Domalpally, A., additional, Goulding, A., additional, Neill, S., additional, Vargo, P., additional, Wilfley, D., additional, Aldrich-Rasche, D., additional, Franklin, K., additional, Massmann, C., additional, O'Brien, D., additional, Patterson, J., additional, Tibbs, T., additional, Van Buren, D., additional, Palmert, M., additional, Ratner, R., additional, Dremaine, D., additional, and Silverstein, J., additional

Published
2018
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8. Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial

Author

Bjornstad, Petter, primary, Nehus, Edward, additional, El ghormli, Laure, additional, Bacha, Fida, additional, Libman, Ingrid M., additional, McKay, Siripoom, additional, Willi, Steven M., additional, Laffel, Lori, additional, Arslanian, Silva, additional, Nadeau, Kristen J., additional, McKay, S., additional, Haymond, M., additional, Anderson, B., additional, Bush, C., additional, Gunn, S., additional, Holden, H., additional, Jones, S.M., additional, Jeha, G., additional, McGirk, S., additional, Thamotharan, S., additional, Cuttler, L., additional, Abrams, E., additional, Casey, T., additional, Dahms, W., additional, Ievers-Landis, C., additional, Kaminski, B., additional, Koontz, M., additional, MacLeish, S., additional, McGuigan, P., additional, Narasimhan, S., additional, Geffner, M., additional, Barraza, V., additional, Chang, N., additional, Conrad, B., additional, Dreimane, D., additional, Estrada, S., additional, Fisher, L., additional, Fleury-Milfort, E., additional, Hernandez, S., additional, Hollen, B., additional, Kaufman, F., additional, Law, E., additional, Mansilla, V., additional, Miller, D., additional, Muñoz, C., additional, Ortiz, R., additional, Ward, A., additional, Wexler, K., additional, Xu, Y.K., additional, Yasuda, P., additional, Levitt Katz, L., additional, Berkowitz, R., additional, Boyd, S., additional, Johnson, B., additional, Kaplan, J., additional, Keating, C., additional, Lassiter, C., additional, Lipman, T., additional, McGinley, G., additional, McKnight, H., additional, Schwartzman, B., additional, Willi, S., additional, Arslanian, S., additional, Bacha, F., additional, Foster, S., additional, Galvin, B., additional, Hannon, T., additional, Kriska, A., additional, Libman, I., additional, Marcus, M., additional, Porter, K., additional, Songer, T., additional, Venditti, E., additional, Goland, R., additional, Gallagher, D., additional, Kringas, P., additional, Leibel, N., additional, Ng, D., additional, Ovalles, M., additional, Seidman, D., additional, Laffel, L., additional, Goebel-Fabbri, A., additional, Hall, M., additional, Higgins, L., additional, Keady, J., additional, Malloy, M., additional, Milaszewski, K., additional, Rasbach, L., additional, Nathan, D.M., additional, Angelescu, A., additional, Bissett, L., additional, Ciccarelli, C., additional, Delahanty, L., additional, Goldman, V., additional, Hardy, O., additional, Larkin, M., additional, Levitsky, L., additional, McEachern, R., additional, Norman, D., additional, Nwosu, D., additional, Park-Bennett, S., additional, Richards, D., additional, Sherry, N., additional, Steiner, B., additional, Tollefsen, S., additional, Carnes, S., additional, Dempsher, D., additional, Flomo, D., additional, Whelan, T., additional, Wolff, B., additional, Weinstock, R., additional, Bowerman, D., additional, Bristol, S., additional, Bulger, J., additional, Hartsig, J., additional, Izquierdo, R., additional, Kearns, J., additional, Saletsky, R., additional, Trief, P., additional, Zeitler, P., additional, Abramson, N., additional, Bradhurst, A., additional, Celona-Jacobs, N., additional, Higgins, J., additional, Kelsey, M., additional, Klingensmith, G., additional, Nadeau, K., additional, Witten, T., additional, Copeland, K., additional, Boss, E., additional, Brown, R., additional, Chadwick, J., additional, Chalmers, L., additional, Chernausek, S., additional, Hebensperger, A., additional, Macha, C., additional, Newgent, R., additional, Nordyke, A., additional, Olson, D., additional, Poulsen, T., additional, Pratt, L., additional, Preske, J., additional, Schanuel, J., additional, Sternlof, S., additional, Lynch, J., additional, Amodei, N., additional, Barajas, R., additional, Cody, C., additional, Hale, D., additional, Hernandez, J., additional, Ibarra, C., additional, Morales, E., additional, Rivera, S., additional, Rupert, G., additional, Wauters, A., additional, White, N., additional, Arbeláez, A., additional, Jones, J., additional, Jones, T., additional, Sadler, M., additional, Tanner, M., additional, Timpson, A., additional, Welch, R., additional, Caprio, S., additional, Grey, M., additional, Guandalini, C., additional, Lavietes, S., additional, Rose, P., additional, Syme, A., additional, Tamborlane, W., additional, Hirst, K., additional, Edelstein, S., additional, Feit, P., additional, Grover, N., additional, Long, C., additional, Pyle, L., additional, Linder, B., additional, Marcovina, S.M., additional, Harting, J., additional, Shepherd, J., additional, Fan, B., additional, Marquez, L., additional, Sherman, M., additional, Wang, J., additional, Nichols, M., additional, Mayer-Davis, E., additional, Liu, Y., additional, Lima, J., additional, Gidding, S., additional, Puccella, J., additional, Ricketts, E., additional, Danis, R., additional, Domalpally, A., additional, Goulding, A., additional, Neill, S., additional, Vargo, P., additional, Wilfley, D., additional, Aldrich-Rasche, D., additional, Franklin, K., additional, Massmann, C., additional, O’Brien, D., additional, Patterson, J., additional, Tibbs, T., additional, Van Buren, D., additional, Palmert, M., additional, Ratner, R., additional, Dremaine, D., additional, and Silverstein, J., additional

Published
2018
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9. SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome

Author

Shaw, N.D., Brand, H., Kupchinsky, Z.A., Bengani, H., Plummer, L., Jones, T.I., Erdin, S., Williamson, K.A., Rainger, J., Stortchevoi, A., Samocha, K., Currall, B.B., Dunican, D.S., Collins, R.L., Willer, J.R., Lek, A., Lek, M., Nassan, M., Pereira, S., Kammin, T., Lucente, D., Silva, A., Seabra, C.M., Chiang, C., An, Y., Ansari, M., Rainger, J.K., Joss, S., Smith, J.C., Lippincott, M.F., Singh, S.S., Patel, N., Jing, J.W., Law, J.R., Ferraro, N., Verloes, A., Rauch, A., Steindl, K., Zweier, M., Scheer, I., Sato, D., Okamoto, N., Jacobsen, C., Tryggestad, J., Chernausek, S., Schimmenti, L.A., Brasseur, B., Cesaretti, C., Garcia-Ortiz, J.E., Buitrago, T.P., Silva, O.P., Hoffman, J.D., Muhlbauer, W., Ruprecht, K.W., Loeys, B.L., Shino, M., Kaindl, A.M., Cho, C.H., Morton, C.C., Meehan, R.R., Heyningen, V. van, Liao, E.C., Balasubramanian, R., Hall, J.E., Seminara, S.B., Macarthur, D., Moore, S.A., Yoshiura, K.I., Gusella, J.F., Marsh, J.A., Graham, J.M., Lin, A.E., Katsanis, N., Jones, P.L., Crowley, W.F., Davis, E.E., FitzPatrick, D.R., Talkowski, M.E., Shaw, N.D., Brand, H., Kupchinsky, Z.A., Bengani, H., Plummer, L., Jones, T.I., Erdin, S., Williamson, K.A., Rainger, J., Stortchevoi, A., Samocha, K., Currall, B.B., Dunican, D.S., Collins, R.L., Willer, J.R., Lek, A., Lek, M., Nassan, M., Pereira, S., Kammin, T., Lucente, D., Silva, A., Seabra, C.M., Chiang, C., An, Y., Ansari, M., Rainger, J.K., Joss, S., Smith, J.C., Lippincott, M.F., Singh, S.S., Patel, N., Jing, J.W., Law, J.R., Ferraro, N., Verloes, A., Rauch, A., Steindl, K., Zweier, M., Scheer, I., Sato, D., Okamoto, N., Jacobsen, C., Tryggestad, J., Chernausek, S., Schimmenti, L.A., Brasseur, B., Cesaretti, C., Garcia-Ortiz, J.E., Buitrago, T.P., Silva, O.P., Hoffman, J.D., Muhlbauer, W., Ruprecht, K.W., Loeys, B.L., Shino, M., Kaindl, A.M., Cho, C.H., Morton, C.C., Meehan, R.R., Heyningen, V. van, Liao, E.C., Balasubramanian, R., Hall, J.E., Seminara, S.B., Macarthur, D., Moore, S.A., Yoshiura, K.I., Gusella, J.F., Marsh, J.A., Graham, J.M., Lin, A.E., Katsanis, N., Jones, P.L., Crowley, W.F., Davis, E.E., FitzPatrick, D.R., and Talkowski, M.E.

Abstract

Item does not contain fulltext, Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes.

Published
2017

12. Proteolytic cleavage of insulin-like growth factor binding protein 4 (IGFBP-4). Localization of cleavage site to non-homologous region of native IGFBP-4

Author

Wright, G., Clemmons, D. R., Busby, W. H., Smith, C. E., Chernausek, S. D., and Duffin, K. L.

Abstract

Insulin-like growth factor binding protein 4 (IGFBP-4) is a 24-kDa protein that binds insulin-like growth factor 1 (IGF-1) and IGF-2 with high affinity and inhibits IGF action in vitro. We recently described a protease produced by the B104 neuronal cell line that cleaves IGFBP-4, yielding an approximate 16-kDa immunoreactive protein that binds IGFs with reduced affinity. We analyzed fragments produced by exposing pure IGFBP-4 to the protease to determine potential cleavage sites. Electrospray mass spectrometry and amino acid sequencing indicated the 16-kDa fragment spanned the NH2 terminus of native IGFBP-4 through Lys-120. There was evidence for an additional proteolytic fragment beginning at amino acid 132 and continuing to the COOH terminus. Proteolysis could be blocked by a synthetic peptide that spanned amino acids 117-126 but not by peptides that contained flanking sequences 111-120 or 125-135. Mutagenesis was used to alter the basic residue at position 120. The expressed mutant IGFBP-4 (K120A) was relatively resistant to cleavage, strongly suggesting that residues 120-121 represent the cleavage site. This region of IGFBP-4 is not homologous with other IGFBPs, explaining the apparent specificity of the protease for IGFBP-4. The 16-kDa IGFBP-4 fragment no longer inhibited IGF-1-stimulated thymidine uptake in vitro, suggesting that proteolytic processing of IGFBP-4 may have important functional consequences in vivo.

Published
1995
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32. Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity.

Author

Yakar, Shoshana, Liu, Jun-Li, Fernandez, Ana M., Wu, Yiping, Schally, Andrew V., Frystyk, Jan, Chernausek, Steve D., Mejia, Wilson, Le Roith, Derek, Yakar, S, Liu, J L, Fernandez, A M, Wu, Y, Schally, A V, Frystyk, J, Chernausek, S D, Mejia, W, and Le Roith, D

Subjects
SOMATOMEDIN, INSULIN resistance, ANIMAL models in research, LIVER physiology, SKELETAL muscle physiology, ANIMAL experimentation, BIOLOGICAL models, BLOOD sugar, CARRIER proteins, CELLULAR signal transduction, COMPARATIVE studies, GLUCOSE tolerance tests, INSULIN, ISLANDS of Langerhans, RESEARCH methodology, MEDICAL cooperation, MICE, GENETIC mutation, RESEARCH, RNA, EVALUATION research, HUMAN growth hormone, PHYSIOLOGY
Abstract

Insulin and insulin-like growth factors (IGFs) mediate a variety of signals involved in mammalian development and metabolism. To study the metabolic consequences of IGF-I deficiency, we used the liver IGF-I-deficient (LID) mouse model. The LID mice show a marked reduction (approximately 75%) in circulating IGF-I and elevated growth hormone (GH) levels. Interestingly, LID mice show a fourfold increase in serum insulin levels (2.2 vs. 0.6 ng/ml in control mice) and abnormal glucose clearance after insulin injection. Fasting blood glucose levels and those after a glucose tolerance test were similar between the LID mice and their control littermates. Thus, the high levels of circulating insulin enable the LID mice to maintain normoglycemia in the presence of apparent insulin insensitivity. Insulin-induced autophosphorylation of the insulin receptor and tyrosine phosphorylation of insulin receptor substrate (IRS)-1 were absent in muscle, but were normal in liver and white adipose tissue of the LID mice. In contrast, IGF-I-induced autophosphorylation of its cognate receptor and phosphorylation of IRS-1 were normal in muscle of LID mice. Thus, the insulin insensitivity seen in the LID mice is muscle specific. Recombinant human IGF-I treatment of the LID mice caused a reduction in insulin levels and an increase in insulin sensitivity. Treatment of the LID mice with GH-releasing hormone antagonist, which reduces GH levels, also increased insulin sensitivity. These data provide evidence of the role of circulating IGF-I as an important component of overall insulin action in peripheral tissues. [ABSTRACT FROM AUTHOR]

Published
2001
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36. Growth hormone therapy of Turner's syndrome: Beneficial effect on adult height

Author

Rosenfeld, R.G., Attie, K.M., Frane, J., Brasel, A., Burstein, S., Cara, J.F., Chernausek, S., Gotlin, R.W., Kuntze, J., Lippe, B.M., Mahoney, C., Moore, W.V., Saenger, P., and Johanson, A.J.

Abstract

Objective: To carry out a multicenter, prospective, randomized trial of human growth hormone (GH), alone or in combination with oxandrolone (OX), in patients with Turner's syndrome (TS). Methods: In an initial phase lasting 12 to 24 months, 70 girls with TS, verified by karyotype, were randomly assigned to one of four groups: (1) observation, (2) OX, (3) GH, or (4) GH plus OX. After completion of the first phase, group 3 subjects continued to receive GH only. All other subjects were treated with GH plus OX. Subjects were followed up until attainment of adult height and/or cessation of treatment. Data from this trial were compared with growth characteristics of 25 American historical subjects with TS (matched for age, height, parental target height, and karyotype) who never received either GH or androgens. Results: Of the 70 subjects enrolled, 60 completed the clinical trial. The 17 subjects receiving GH alone all completed the trial and reached a height of 150.4 +/- 5.5 cm (mean +/- SD), 8.4 +/- 4.5 cm taller than their mean projected adult height at enrollment (95% confidence interval [CI]: 6.3 to 10.6 cm). The 43 subjects receiving GH plus OX attained a mean height of 152.1 +/- 5.9 cm, 10.3 +/- 4.7 cm taller than their mean projected adult height (95% CI: 8.9 to 11.7 cm). The historical control subjects had a mean adult height of 144.2 +/- 6.0 cm, precisely matching their original projected adult height of 144.2 +/- 6.1 cm. Conclusions: GH, either alone or in combination with OX, is capable of stimulating short-term growth and augmenting adult height in girls with TS. With early diagnosis and initiation of treatment, an adult height of more than 150 cm is a reasonable goal for most girls with TS. (J Pediatr 1998;132:319-24)

Published
1998
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37. Partial growth-hormone insensitivity: The role of growth-hormone receptor mutations in idiopathic short stature

Author

Genentech, Inc., Francisco, South San, California, Endocrinology, the Department of Pediatric, From the Departments of Molecular Biology, Childre, Science, Clinical, Goddard, A.D., Dowd, P., Chernausek, S., Geffner, M., Gertner, J., Hintz, R., Hopwood, N., Kaplan, S., Plotnick, L., Rogol, A., Rosenfield, R., Saenger, P., Mauras, N., Hershkopf, R., Angulo, M., and Attie, K.

Abstract

Mutations in the GHR locus may play a role in the cause of idiopathic short stature (ISS) by impairing growth-hormone (GH) receptor (GHR) function. At one extreme, mutations that nullify the function of the GH receptor are linked to complete GH insensitivity syndrome, or Laron syndrome, and we hypothesized that less-disruptive mutations could contribute to partial GH insensitivity syndrome. Low levels of GH binding protein may indicate mutations in the extracellular domain of the receptor, and by focusing on 14 children with ISS who had low GH binding protein and insulin-like growth factor I levels, we found three heterozygotes and one compound heterozygote for mutations in the extracellular domain of the receptor. We have since extended our study to a broader spectrum of patients, adding 76 patients with ISS who were treated with GH in a phase II study of the safety and efficacy of recombinant human GH in ISS and also adding 10 patients who were ascertained as having ISS by pediatric endocrinologists in private practice. The GHR gene has thus been analyzed in 100 patients with ISS, eight of whom were found to carry mutations: four in our original study and four with normal or elevated levels of GH binding protein. The latter group consists of three carriers of heterozygous extracellular domain mutations and one carrier of a heterozygous intracellular domain mutation. Family data suggest that the carriers of these mutations have a range of phenotypes, supporting our hypothesis that the expression of these heterozygous mutations as partial GH insensitivity syndrome depends on the genetic makeup of the person. (J Pediatr 1997;131:S51-5)

Published
1997
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38. Proteolytic cleavage of insulin-like growth factor binding protein 4 (IGFBP-4). Localization of cleavage site to non-homologous region of native IGFBP-4.

Author

Chernausek, S D, Smith, C E, Duffin, K L, Busby, W H, Wright, G, and Clemmons, D R

Abstract

Insulin-like growth factor binding protein 4 (IGFBP-4) is a 24-kDa protein that binds insulin-like growth factor 1 (IGF-1) and IGF-2 with high affinity and inhibits IGF action in vitro. We recently described a protease produced by the B104 neuronal cell line that cleaves IGFBP-4, yielding an approximate 16-kDa immunoreactive protein that binds IGFs with reduced affinity. We analyzed fragments produced by exposing pure IGFBP-4 to the protease to determine potential cleavage sites. Electrospray mass spectrometry and amino acid sequencing indicated the 16-kDa fragment spanned the NH2 terminus of native IGFBP-4 through Lys-120. There was evidence for an additional proteolytic fragment beginning at amino acid 132 and continuing to the COOH terminus. Proteolysis could be blocked by a synthetic peptide that spanned amino acids 117-126 but not by peptides that contained flanking sequences 111-120 or 125-135. Mutagenesis was used to alter the basic residue at position 120. The expressed mutant IGFBP-4 (K120A) was relatively resistant to cleavage, strongly suggesting that residues 120-121 represent the cleavage site. This region of IGFBP-4 is not homologous with other IGFBPs, explaining the apparent specificity of the protease for IGFBP-4. The 16-kDa IGFBP-4 fragment no longer inhibited IGF-1-stimulated thymidine uptake in vitro, suggesting that proteolytic processing of IGFBP-4 may have important functional consequences in vivo.

Published
1995

39. Diverse growth hormone receptor gene mutations in Laron syndrome

Author

Ma, Berg, Jesús Argente, Chernausek S, Gracia R, Guevara-Aguirre J, Hopp M, Pérez-Jurado L, Rosenbloom A, Sp, Toledo, and Francke U

Subjects
Adult, Male, Polymorphism, Genetic, Adolescent, Base Sequence, DNA Mutational Analysis, Molecular Sequence Data, Exons, Receptors, Somatotropin, Polymerase Chain Reaction, Haplotypes, Child, Preschool, Mutation, Humans, Point Mutation, Electrophoresis, Polyacrylamide Gel, Female, Child, Dwarfism, Pituitary, Frameshift Mutation, Sequence Deletion, Research Article
Abstract

To better understand the molecular genetic basis and genetic epidemiology of Laron syndrome (growth-hormone insensitivity syndrome), we analyzed the growth-hormone receptor (GHR) genes of seven unrelated affected individuals from the United States, South America, Europe, and Africa. We amplified all nine GHR gene exons and splice junctions from these individuals by PCR and screened the products for mutations by using denaturing gradient gel electrophoresis (DGGE). We identified a single GHR gene fragment with abnormal DGGE results for each affected individual, sequenced this fragment, and, in each case, identified a mutation likely to cause Laron syndrome, including two nonsense mutations (R43X and R217X), two splice-junction mutations, (189-1 G to T and 71 + 1 G to A), and two frameshift mutations (46 del TT and 230 del TA or AT). Only one of these mutations, R43X, has been previously reported. Using haplotype analysis, we determined that this mutation, which involves a CpG dinucleotide hot spot, likely arose as a separate event in this case, relative to the two prior reports of R43X. Aside from R43X, the mutations we identified are unique to patients from particular geographic regions. Ten GHR gene mutations have now been described in this disorder. We conclude that Laron syndrome is caused by diverse GHR gene mutations, including deletions, RNA processing defects, translational stop codons, and missense codons. All the identified mutations involve the extracellular domain of the receptor, and most are unique to particular families or geographic areas.

47. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting

Author

Gravholt, Claus H, Andersen, Niels H, Conway, Gerard S, Dekkers, Olaf M, Geffner, Mitchell E, Klein, Karen O, Lin, Angela E, Mauras, Nelly, Quigley, Charmian A, Rubin, Karen, Sandberg, David E, Sas, Theo C J, Silberbach, Michael, Söderström-Anttila, Viveca, Stochholm, Kirstine, Van Alfen-Van DerVelden, Janielle A, Woelfle, Joachim, Backeljauw, Philippe F, Bamba, Vaneeta, Bonfig, Natalie Brobin, Braverman, Alan C, Breech, Lesley L, Brickman, Wendy J, Brown, Nicole M, Bryant, Nancy, Cernich, Joseph, Chernausek, Steven, Christin-Maitre, Sophie, Corathers, Sarah D, Crawford, Anne, Crenshaw, Melissa L, Davenport, Marsha L, De Backer, Julie, Eagle, Kim, Gawlik, Aneta, Gutmark-Little, Iris, Hay, Darlene, Hiratzka, Loren, Hong, David S, Hovatta, Outi, Hultcrantz, Malou, Johnson, Walter H, Kanaka-Gantenbein, Christina, Karnis, Megan F, Knickmeyer, Rebecca Christine, Kristrøm, Berit, Lajiness-O'Neill, Renee R., Landin-Wilhelmsen, Kerstin, Law, Jennifer R, Lippe, Barbara, Lopez, Leo, Mawson, Lisa, Mazzanti, Laura, Mortensen, Kristian Havmand, Popovic, Jadranka, Prakash, Siddharth, Ranallo, Kelly C., Rappold, Gudrun Anna, Roos-Hesselink, Jolien, Rosenfield, Robert, Ross, Judith, Roulot-Marullo, Dominique, Saidi, Arwa, Santen, Richard J, Scurlock, Cindy C, Sheanon, Nicole M, Smyth, Arlene, Van Hagen, Iris M, Verlinde, Franciska, Wasniewska, Malgorzata, Young, Luciana T, Pediatrics, and Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, Lin AE, Mauras N, Quigley CA, Rubin K, Sandberg DE, Sas TCJ, Silberbach M, Söderström-Anttila V, Stochholm K, van Alfen-van derVelden JA, Woelfle J, Backeljauw PF, Bamba V, Brobin B, Braverman AC, Lesley L Breech LL, Brickman WJ, Brown NM, Bryant N, Cernich JT, Chernausek S, Christin-Maitre S, Corathers SD, Crawford A, Crenshaw ML, Davenport ML, de Backer J, Eagle K, Gawlik A, Gutmark-Little I, Hay D, Hiratzka L, Hong DS, Hovatta O, Hultcrantz M, Johnson WH Jr, Kanaka-Gantenbein C, Karnis MF, Knickmeyer RC, Kristrøm B, Lajiness-O’Neill RR, Landin-Wilhelmsen K, Law JR, Lippe B, Lopez L, Mawson L, Mazzanti L, Mortensen KH, Popovic J, Prakash S, Ranallo KC, Rappold GA, Roos-Hesselink J, Rosenfield R, Ross J, Roulot-Marullo D, Saidi A, Santen RJ, Scurlock CC, Sheanon NM, Smyth A, van Hagen IM, Verlinde F, Wasniewska M and Young LT.

Subjects
medicine.medical_specialty, Pediatrics, Pediatric endocrinology, Endocrinology, Diabetes and Metabolism, MEDLINE, Specialty, Turner Syndrome, 030209 endocrinology & metabolism, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, Human reproduction, 0302 clinical medicine, Endocrinology, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Turner syndrome, medicine, Journal Article, Humans, Women, Grading (education), Ohio, business.industry, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], General Medicine, Guideline, Congresses as Topic, medicine.disease, United States, Europe, Diabetes and Metabolism, turner syndrome, Family medicine, Congresses as Topic, Europe, Female, Humans, Ohio, Patient Care, Practice Guidelines as Topic, Turner Syndrome, United States, Women, Endocrinology, Diabetes and Metabolism, Endocrinology, Practice Guidelines as Topic, Female, Patient Care, business
Abstract

Turner syndrome affects 25–50 per 100,000 females and can involve multiple organs through all stages of life, necessitating multidisciplinary approach to care. Previous guidelines have highlighted this, but numerous important advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines project was initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, in collaboration with the European Society for Paediatric Endocrinology, the Endocrine Society, the European Society of Human Reproduction and Embryology, the American Heart Association, the Society for Endocrinology, and the European Society of Cardiology. The guideline has been formally endorsed by the European Society of Endocrinology, the Pediatric Endocrine Society, the European Society for Paediatric Endocrinology, the European Society of Human Reproduction and Embryology and the Endocrine Society. Advocacy groups appointed representatives who participated in pre-meeting discussions and in the consensus meeting.

Published
2017
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48. Assessing the prediction of type 2 diabetes risk using polygenic and clinical risk scores in South Asian study populations.

Author

Rout M, Wander GS, Ralhan S, Singh JR, Aston CE, Blackett PR, Chernausek S, and Sanghera DK

Abstract

Background: Genome-wide polygenic risk scores (PRS) have shown high specificity and sensitivity in predicting type 2 diabetes (T2D) risk in Europeans. However, the PRS-driven information and its clinical significance in non-Europeans are underrepresented. We examined the predictive efficacy and transferability of PRS models using variant information derived from genome-wide studies of Asian Indians (AIs) (PRS AI ) and Europeans (PRS EU ) using 13,974 AI individuals., Methods: Weighted PRS models were constructed and analyzed on 4602 individuals from the Asian Indian Diabetes Heart Study/Sikh Diabetes Study (AIDHS/SDS) as discovery/training and test/validation datasets. The results were further replicated in 9372 South Asian individuals from UK Biobank (UKBB). We also assessed the performance of each PRS model by combining data of the clinical risk score (CRS)., Results: Both genetic models (PRS AI and PRS EU ) successfully predicted the T2D risk. However, the PRS AI revealed 13.2% odds ratio (OR) 1.80 [95% confidence interval (CI) 1.63-1.97; p  = 1.6 × 10 -152 ] and 12.2% OR 1.38 (95% CI 1.30-1.46; p  = 7.1 × 10 -237 ) superior performance in AIDHS/SDS and UKBB validation sets, respectively. Comparing individuals of extreme PRS (ninth decile) with the average PRS (fifth decile), PRS AI showed about two-fold OR 20.73 (95% CI 10.27-41.83; p  = 2.7 × 10 -17 ) and 1.4-fold OR 3.19 (95% CI 2.51-4.06; p  = 4.8 × 10 -21 ) higher predictability to identify subgroups with higher genetic risk than the PRS EU . Combining PRS and CRS improved the area under the curve from 0.74 to 0.79 in PRS AI and 0.72 to 0.75 in PRS EU ., Conclusion: Our data suggest the need for extending genetic and clinical studies in varied ethnic groups to exploit the full clinical potential of PRS as a risk prediction tool in diverse study populations., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Published
2023
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49. Re-analysis and meta-analysis of summary statistics from gene-environment interaction studies.

Author

Pham DT, Westerman KE, Pan C, Chen L, Srinivasan S, Isganaitis E, Vajravelu ME, Bacha F, Chernausek S, Gubitosi-Klug R, Divers J, Pihoker C, Marcovina SM, Manning AK, and Chen H

Subjects
Models, Statistical, Sample Size, Data Interpretation, Statistical, Polymorphism, Single Nucleotide, Phenotype, Gene-Environment Interaction, Genome-Wide Association Study
Abstract

Motivation: statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene-environment interactions, there is a need for gene-environment interaction-specific methods that manipulate and use summary statistics., Results: We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene-exposure and/or gene-covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction covariate adjustments. METAGEM (META-analysis of GEM summary statistics) extends current fixed-effects meta-analysis models to incorporate multiple exposures from multiple studies. We demonstrate the value and efficiency of these tools by exploring alternative methods of accounting for ancestry-related population stratification in genome-wide interaction study in the UK Biobank as well as by conducting a multi-exposure genome-wide interaction study meta-analysis in cohorts from the diabetes-focused ProDiGY consortium. These programs help to maximize the value of summary statistics from diverse and complex gene-environment interaction studies., Availability and Implementation: REGEM and METAGEM are open-source projects freely available at https://github.com/large-scale-gxe-methods/REGEM and https://github.com/large-scale-gxe-methods/METAGEM., (© The Author(s) 2023. Published by Oxford University Press.)

Published
2023
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