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2. Prosaposin is a regulator of progranulin levels and oligomerization.

Author

Nicholson, Alexandra M, Finch, NiCole A, Almeida, Marcio, Perkerson, Ralph B, van Blitterswijk, Marka, Wojtas, Aleksandra, Cenik, Basar, Rotondo, Sergio, Inskeep, Venette, Almasy, Laura, Dyer, Thomas, Peralta, Juan, Jun, Goo, Wood, Andrew R, Frayling, Timothy M, Fuchsberger, Christian, Fowler, Sharon, Teslovich, Tanya M, Manning, Alisa K, Kumar, Satish, Curran, Joanne, Lehman, Donna, Abecasis, Goncalo, Duggirala, Ravindranath, Pottier, Cyril, Zahir, Haaris A, Crook, Julia E, Karydas, Anna, Mitic, Laura, Sun, Ying, Dickson, Dennis W, Bu, Guojun, Herz, Joachim, Yu, Gang, Miller, Bruce L, Ferguson, Shawn, Petersen, Ronald C, Graff-Radford, Neill, Blangero, John, and Rademakers, Rosa

Subjects
Hela Cells, Animals, Mice, Knockout, Humans, Mice, Parkinson Disease, Alzheimer Disease, Saposins, Intercellular Signaling Peptides and Proteins, Polymorphism, Single Nucleotide, Gene Knockdown Techniques, Frontotemporal Dementia, Haploinsufficiency, Protein Interaction Maps, Progranulins, HeLa Cells, Biotechnology, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Neurodegenerative, Brain Disorders, Acquired Cognitive Impairment, Dementia, 2.1 Biological and endogenous factors, Neurological, Knockout, Polymorphism, Single Nucleotide
Abstract

Progranulin (GRN) loss-of-function mutations leading to progranulin protein (PGRN) haploinsufficiency are prevalent genetic causes of frontotemporal dementia. Reports also indicated PGRN-mediated neuroprotection in models of Alzheimer's and Parkinson's disease; thus, increasing PGRN levels is a promising therapeutic for multiple disorders. To uncover novel PGRN regulators, we linked whole-genome sequence data from 920 individuals with plasma PGRN levels and identified the prosaposin (PSAP) locus as a new locus significantly associated with plasma PGRN levels. Here we show that both PSAP reduction and overexpression lead to significantly elevated extracellular PGRN levels. Intriguingly, PSAP knockdown increases PGRN monomers, whereas PSAP overexpression increases PGRN oligomers, partly through a protein-protein interaction. PSAP-induced changes in PGRN levels and oligomerization replicate in human-derived fibroblasts obtained from a GRN mutation carrier, further supporting PSAP as a potential PGRN-related therapeutic target. Future studies should focus on addressing the relevance and cellular mechanism by which PGRN oligomeric species provide neuroprotection.

Published
2016

3. Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children

Author

Mummidi, Srinivas, Farook, Vidya S., Reddivari, Lavanya, Hernandez-Ruiz, Joselin, Diaz-Badillo, Alvaro, Fowler, Sharon P., Resendez, Roy G., Akhtar, Feroz, Lehman, Donna M., Jenkinson, Christopher P., Arya, Rector, Lynch, Jane L., Canas, Jose A., DeFronzo, Ralph A., Hale, Daniel E., Blangero, John, Lopez-Alvarenga, Juan Carlos, Duggirala, Ravindranath, and Vanamala, Jairam K. P.

Published
2021
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4. Genetics of serum carotenoid concentrations and their correlation with obesity-related traits in Mexican American children

Author

Farook, Vidya S, Reddivari, Lavanya, Mummidi, Srinivas, Puppala, Sobha, Arya, Rector, Lopez-Alvarenga, Juan Carlos, Fowler, Sharon P, Chittoor, Geetha, Resendez, Roy G, Kumar, Birunda Mohan, Comuzzie, Anthony G, Curran, Joanne E, Lehman, Donna M, Jenkinson, Christopher P, Lynch, Jane L, DeFronzo, Ralph A, Blangero, John, Hale, Daniel E, Duggirala, Ravindranath, and Vanamala, Jairam KP

Published
2017
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5. The genetic architecture of type 2 diabetes

Author

Fuchsberger, Christian, Flannick, Jason, Teslovich, Tanya M., Mahajan, Anubha, Agarwala, Vineeta, Gaulton, Kyle J., Ma, Clement, Fontanillas, Pierre, Moutsianas, Loukas, McCarthy, Davis J., Rivas, Manuel A., Perry, John R. B., Sim, Xueling, Blackwell, Thomas W., Robertson, Neil R., Rayner, N. William, Cingolani, Pablo, Locke, Adam E., Tajes, Juan Fernandez, Highland, Heather M., Dupuis, Josee, Chines, Peter S., Lindgren, Cecilia M., Hartl, Christopher, Jackson, Anne U., Chen, Han, Huyghe, Jeroen R., van de Bunt, Martijn, Pearson, Richard D., Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M., Gamazon, Eric R., Lee, Jaehoon, Chen, Yuhui, Scott, Robert A., Below, Jennifer E., Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L., Pasko, Dorota, Parker, Stephen C. J., Varga, Tibor V., Green, Todd, Beer, Nicola L., Day-Williams, Aaron G., Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong-Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min-Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng-Han, Maxwell, Taylor J., Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P., Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F., Han, Bok-Ghee, Jenkinson, Christopher P., Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie C. Y., Palmer, Nicholette D., Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E., Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D., Neale, Benjamin M., Purcell, Shaun, Butterworth, Adam S., Howson, Joanna M. M., Lee, Heung Man, Lu, Yingchang, Kwak, Soo-Heon, Zhao, Wei, Danesh, John, Lam, Vincent K. L., Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia H. T., Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching-Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E., Rybin, Denis, Farook, Vidya S., Fowler, Sharon P., Freedman, Barry I., Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J., Khor, Chiea-Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, van der Schouw, Yvonne T., Loh, Marie, Musani, Solomon K., Puppala, Sobha, Scott, William R., Yengo, Loïc, Tan, Sian-Tsung, Taylor Jr., Herman A., Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C., Mangino, Massimo, Bonnycastle, Lori L., Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L., Herder, Christian, Groves, Christopher J., Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A., Doney, Alex S. F., Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J., Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeriya, Hollensted, Mette, Jørgensen, Marit E., Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Swift, Amy, Rosengren, Anders H., Stirrups, Kathleen, Wood, Andrew R., Mihailov, Evelin, Blancher, Christine, Carneiro, Mauricio O., Maguire, Jared, Poplin, Ryan, Shakir, Khalid, Fennell, Timothy, DePristo, Mark, Hrabé de Angelis, Martin, Deloukas, Panos, Gjesing, Anette P., Jun, Goo, Nilsson, Peter, Murphy, Jacquelyn, Onofrio, Robert, Thorand, Barbara, Hansen, Torben, Meisinger, Christa, Hu, Frank B., Isomaa, Bo, Karpe, Fredrik, Liang, Liming, Peters, Annette, Huth, Cornelia, O’Rahilly, Stephen P., Palmer, Colin N. A., Pedersen, Oluf, Rauramaa, Rainer, Tuomilehto, Jaakko, Salomaa, Veikko, Watanabe, Richard M., Syvänen, Ann-Christine, Bergman, Richard N., Bharadwaj, Dwaipayan, Bottinger, Erwin P., Cho, Yoon Shin, Chandak, Giriraj R., Chan, Juliana C. N., Chia, Kee Seng, Daly, Mark J., Ebrahim, Shah B., Langenberg, Claudia, Elliott, Paul, Jablonski, Kathleen A., Lehman, Donna M., Jia, Weiping, Ma, Ronald C. W., Pollin, Toni I., Sandhu, Manjinder, Tandon, Nikhil, Froguel, Philippe, Barroso, Inês, Teo, Yik Ying, Zeggini, Eleftheria, Loos, Ruth J. F., Small, Kerrin S., Ried, Janina S., DeFronzo, Ralph A., Grallert, Harald, Glaser, Benjamin, Metspalu, Andres, Wareham, Nicholas J., Walker, Mark, Banks, Eric, Gieger, Christian, Ingelsson, Erik, Im, Hae Kyung, Illig, Thomas, Franks, Paul W., Buck, Gemma, Trakalo, Joseph, Buck, David, Prokopenko, Inga, Mägi, Reedik, Lind, Lars, Farjoun, Yossi, Owen, Katharine R., Gloyn, Anna L., Strauch, Konstantin, Tuomi, Tiinamaija, Kooner, Jaspal Singh, Lee, Jong-Young, Park, Taesung, Donnelly, Peter, Morris, Andrew D., Hattersley, Andrew T., Bowden, Donald W., Collins, Francis S., Atzmon, Gil, Chambers, John C., Spector, Timothy D., Laakso, Markku, Strom, Tim M., Bell, Graeme I., Blangero, John, Duggirala, Ravindranath, Tai, E. Shyong, McVean, Gilean, Hanis, Craig L., Wilson, James G., Seielstad, Mark, Frayling, Timothy M., Meigs, James B., Cox, Nancy J., Sladek, Rob, Lander, Eric S., Gabriel, Stacey, Burtt, Noël P., Mohlke, Karen L., Meitinger, Thomas, Groop, Leif, Abecasis, Goncalo, Florez, Jose C., Scott, Laura J., Morris, Andrew P., Kang, Hyun Min, Boehnke, Michael, Altshuler, David, and McCarthy, Mark I.

Published
2016
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6. Genetic epidemiology of cardiometabolic risk factors and their clustering patterns in Mexican American children and adolescents: the SAFARI Study

Author

Fowler, Sharon P., Puppala, Sobha, Arya, Rector, Chittoor, Geetha, Farook, Vidya S., Schneider, Jennifer, Resendez, Roy G., Upadhayay, Ram Prasad, VandeBerg, Jane, Hunt, Kelly J., Bradshaw, Benjamin, Cersosimo, Eugenio, VandeBerg, John L., Almasy, Laura, Curran, Joanne E., Comuzzie, Anthony G., Lehman, Donna M., Jenkinson, Christopher P., Lynch, Jane L., DeFronzo, Ralph A., Blangero, John, Hale, Daniel E., and Duggirala, Ravindranath

Published
2013
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8. Acanthosis nigricans as a composite marker of cardiometabolic risk and its complex association with obesity and insulin resistance in Mexican American children

Author

Lopez-Alvarenga, Juan C., primary, Chittoor, Geetha, additional, Paul, Solomon F. D., additional, Puppala, Sobha, additional, Farook, Vidya S., additional, Fowler, Sharon P., additional, Resendez, Roy G., additional, Hernandez-Ruiz, Joselin, additional, Diaz-Badillo, Alvaro, additional, Salazar, David, additional, Garza, Doreen D., additional, Lehman, Donna M., additional, Mummidi, Srinivas, additional, Arya, Rector, additional, Jenkinson, Christopher P., additional, Lynch, Jane L., additional, DeFronzo, Ralph A., additional, Blangero, John, additional, Hale, Daniel E., additional, and Duggirala, Ravindranath, additional

Published
2020
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9. 2093-P: Acanthosis Nigricans as a Composite Marker of Cardiometabolic Risk and Its Complex Association with Obesity and Insulin Resistance in Mexican-American Children

Author

LOPEZ-ALVARENGA, JUAN C., primary, ARYA, RECTOR, additional, CHITTOOR, GEETHA, additional, PAUL, SOLOMON FRANKLIN, additional, PUPPALA, SOBHA R., additional, FAROOK, VIDYA S., additional, FOWLER, SHARON P., additional, RESENDEZ, ROY G., additional, DIAZ-BADILLO, ALVARO, additional, LEHMAN, DONNA, additional, MUMMIDI, SRINIVAS, additional, JENKINSON, CHRIS, additional, LYNCH, JANE L., additional, DEFRONZO, RALPH A., additional, BLANGERO, JOHN, additional, HALE, DANIEL E., additional, and DUGGIRALA, RAVINDRANATH, additional

Published
2019
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10. Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

Author

Massachusetts Institute of Technology. Department of Biology, Altshuler, David M, Jason, Flannick, Fuchsberger, Christian, Mahajan, Anubha, Teslovich, Tanya M., Agarwala, Vineeta, Gaulton, Kyle J., Caulkins, Lizz, Koesterer, Ryan, Ma, Clement, Moutsianas, Loukas, McCarthy, Davis J., Rivas, Manuel A., Perry, John R. B., Sim, Xueling, Blackwell, Thomas W., Robertson, Neil R., Rayner, N William, Cingolani, Pablo, Locke, Adam E., Tajes, Juan Fernandez, Highland, Heather M., Dupuis, Josee, Chines, Peter S., Lindgren, Cecilia M., Hartl, Christopher, Jackson, Anne U., Chen, Han, Huyghe, Jeroen R., van de Bunt, Martijn, Pearson, Richard D., Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M., Gamazon, Eric R., Chen, Yuhui, Scott, Robert A., Below, Jennifer E., Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L., Pasko, Dorota, Parker, Stephen C. J., Varga, Tibor V., Green, Todd, Beer, Nicola L., Day-Williams, Aaron G., Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong-Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min-Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng-Han, Maxwell, Taylor J., Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P., Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F., Han, Bok-Ghee, Jenkinson, Christopher P., Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie C. Y., Palmer, Nicholette D., Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E., Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D., Neale, Benjamin M., Purcell, Shaun, Butterworth, Adam S., Howson, Joanna M. M., Lee, Heung Man, Lu, Yingchang, Kwak, Soo-Heon, Zhao, Wei, Danesh, John, Lam, Vincent K. L., Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia H. T., Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching-Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E., Rybin, Dennis, Farook, Vidya S., Fowler, Sharon P., Freedman, Barry I., Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J., Khor, Chiea-Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, Loh, Marie, Musani, Solomon K., Puppala, Sobha, Scott, William R., Yengo, Loïc, Tan, Sian-Tsung, Taylor, Herman A., Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C., Mangino, Massimo, Bonnycastle, Lori L., Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L., Herder, Christian, Groves, Christopher J., Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A., Doney, Alex S. F., Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J., Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeri, Hollensted, Mette, Jørgensen, Marit E., Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Altshuler, David, Lee, Jaehoon, Ph. D. Massachusetts Institute of Technology, Massachusetts Institute of Technology. Department of Biology, Altshuler, David M, Jason, Flannick, Fuchsberger, Christian, Mahajan, Anubha, Teslovich, Tanya M., Agarwala, Vineeta, Gaulton, Kyle J., Caulkins, Lizz, Koesterer, Ryan, Ma, Clement, Moutsianas, Loukas, McCarthy, Davis J., Rivas, Manuel A., Perry, John R. B., Sim, Xueling, Blackwell, Thomas W., Robertson, Neil R., Rayner, N William, Cingolani, Pablo, Locke, Adam E., Tajes, Juan Fernandez, Highland, Heather M., Dupuis, Josee, Chines, Peter S., Lindgren, Cecilia M., Hartl, Christopher, Jackson, Anne U., Chen, Han, Huyghe, Jeroen R., van de Bunt, Martijn, Pearson, Richard D., Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M., Gamazon, Eric R., Chen, Yuhui, Scott, Robert A., Below, Jennifer E., Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L., Pasko, Dorota, Parker, Stephen C. J., Varga, Tibor V., Green, Todd, Beer, Nicola L., Day-Williams, Aaron G., Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong-Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min-Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng-Han, Maxwell, Taylor J., Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P., Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F., Han, Bok-Ghee, Jenkinson, Christopher P., Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie C. Y., Palmer, Nicholette D., Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E., Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D., Neale, Benjamin M., Purcell, Shaun, Butterworth, Adam S., Howson, Joanna M. M., Lee, Heung Man, Lu, Yingchang, Kwak, Soo-Heon, Zhao, Wei, Danesh, John, Lam, Vincent K. L., Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia H. T., Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching-Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E., Rybin, Dennis, Farook, Vidya S., Fowler, Sharon P., Freedman, Barry I., Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J., Khor, Chiea-Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, Loh, Marie, Musani, Solomon K., Puppala, Sobha, Scott, William R., Yengo, Loïc, Tan, Sian-Tsung, Taylor, Herman A., Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C., Mangino, Massimo, Bonnycastle, Lori L., Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L., Herder, Christian, Groves, Christopher J., Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A., Doney, Alex S. F., Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J., Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeri, Hollensted, Mette, Jørgensen, Marit E., Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Altshuler, David, and Lee, Jaehoon, Ph. D. Massachusetts Institute of Technology

Abstract

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals ( > 80% of low-frequency coding variants in ∼82 K Europeans via the exome chip, and ∼90% of low-frequency non-coding variants in ∼44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.

Published
2018

11. Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

Author

Flannick, Jason, Fuchsberger, Christian, Mahajan, Anubha, Teslovich, Tanya M., Agarwala, Vineeta, Gaulton, Kyle J., Caulkins, Lizz, Koesterer, Ryan, Ma, Clement, Moutsianas, Loukas, McCarthy, Davis J., Rivas, Manuel A., Perry, John R.B., Sim, Xueling, Blackwell, Thomas W., Robertson, Neil R., Rayner, N. William, Cingolani, Pablo, Locke, Adam E., Tajes, Juan Fernandez, Highland, Heather M., Dupuis, Josée, Chines, Peter S., Lindgren, Cecilia M., Hartl, Christopher, Jackson, Anne U., Chen, Han, Huyghe, Jeroen R., Van De Bunt, Martijn, Pearson, Richard D., Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M., Gamazon, Eric R., Lee, Jaehoon, Chen, Yuhui, Scott, Robert A., Below, Jennifer E., Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L., Pasko, Dorota, Parker, Stephen C.J., Varga, Tibor V., Green, Todd, Beer, Nicola L., Day-Williams, Aaron G., Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng Han, Maxwell, Taylor J., Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P., Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F., Han, Bok Ghee, Jenkinson, Christopher P., Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie C.Y., Palmer, Nicholette D., Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E., Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D., Neale, Benjamin M., Purcell, Shaun, Butterworth, Adam S., Howson, Joanna M.M., Lee, Heung Man, Lu, Yingchang, Kwak, Soo Heon, Zhao, Wei, Danesh, John, Lam, Vincent K.L., Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia H.T., Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E., Rybin, Dennis, Farook, Vidya S., Fowler, Sharon P., Freedman, Barry I., Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J., Khor, Chiea Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, Loh, Marie, Musani, Solomon K., Puppala, Sobha, Scott, William R., Yengo, Loïc, Tan, Sian Tsung, Taylor, Herman A., Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C., Mangino, Massimo, Bonnycastle, Lori L., Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L., Herder, Christian, Groves, Christopher J., Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A., Doney, Alex S.F., Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J., Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeriya, Hollensted, Mette, Jørgensen, Marit E., Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Swift, Amy, Rosengren, Anders H., Stirrups, Kathleen, Wood, Andrew R., Mihailov, Evelin, Blancher, Christine, Carneiro, Mauricio O., Maguire, Jared, Poplin, Ryan, Shakir, Khalid, Fennell, Timothy, DePristo, Mark, De Angelis, Martin Hrabé, Deloukas, Panos, Gjesing, Anette P., Jun, Goo, Nilsson, Peter M., Murphy, Jacquelyn, Onofrio, Robert, Thorand, Barbara, Hansen, Torben, Meisinger, Christa, Hu, Frank B., Isomaa, Bo, Karpe, Fredrik, Liang, Liming, Peters, Annette, Huth, Cornelia, O'Rahilly, Stephen P., Palmer, Colin N.A., Pedersen, Oluf, Rauramaa, Rainer, Tuomilehto, Jaakko, Salomaa, Veikko, Watanabe, Richard M., Syvänen, Ann Christine, Bergman, Richard N., Bharadwaj, Dwaipayan, Bottinger, Erwin P., Cho, Yoon Shin, Chandak, Giriraj R., Chan, Juliana C.N., Chia, Kee Seng, Daly, Mark J., Ebrahim, Shah B., Langenberg, Claudia, Elliott, Paul, Jablonski, Kathleen A., Lehman, Donna M., Jia, Weiping, Ma, Ronald C.W., Pollin, Toni I., Sandhu, Manjinder, Tandon, Nikhil, Froguel, Philippe, Barroso, Inês, Teo, Yik Ying, Zeggini, Eleftheria, Loos, Ruth J.F., Small, Kerrin S., Ried, Janina S., DeFronzo, Ralph A., Grallert, Harald, Glaser, Benjamin, Metspalu, Andres, Wareham, Nicholas J., Walker, Mark, Banks, Eric, Gieger, Christian, Ingelsson, Erik, Im, Hae Kyung, Illig, Thomas, Franks, Paul W., Buck, Gemma, Trakalo, Joseph, Buck, David, Prokopenko, Inga, Mägi, Reedik, Lind, Lars, Farjoun, Yossi, Owen, Katharine R., Gloyn, Anna L., Strauch, Konstantin, Tuomi, Tiinamaija, Kooner, Jaspal Singh, Lee, Jong Young, Park, Taesung, Donnelly, Peter, Morris, Andrew D., Hattersley, Andrew T., Bowden, Donald W., Collins, Francis S., Atzmon, Gil, Chambers, John C., Spector, Timothy D., Laakso, Markku, Strom, Tim M., Bell, Graeme I., Blangero, John, Duggirala, Ravindranath, Tai, Eshyong, McVean, Gilean, Hanis, Craig L., Wilson, James G., Seielstad, Mark, Frayling, Timothy M., Meigs, James B., Cox, Nancy J., Sladek, Rob, Lander, Eric S., Gabriel, Stacey, Mohlke, Karen L., Meitinger, Thomas, Groop, Leif, Abecasis, Goncalo, Scott, Laura J., Morris, Andrew P., Kang, Hyun Min, Altshuler, David, Burtt, Noël P., Florez, Jose C., Boehnke, Michael, McCarthy, Mark I., Clinicum, Department of Medicine, Endokrinologian yksikkö, Research Programs Unit, Diabetes and Obesity Research Program, Institute for Molecular Medicine Finland, HUS Internal Medicine and Rehabilitation, and HUS Abdominal Center

Subjects
MUTATIONS, COMMON DISEASES, POPULATION-SCALE, Endocrinology and Diabetes, FRAMEWORK, GENETIC ARCHITECTURE, RARE VARIANTS, DISCOVERY, 3121 General medicine, internal medicine and other clinical medicine, Endokrinologi och diabetes, IMPUTATION, GENOME-WIDE ASSOCIATION, Medical Genetics, METAANALYSIS, Medicinsk genetik
Abstract

Correction: SCIENTIFIC DATA Vol. 5, Article Number: 180182, DOI: 10.1038/sdata.2018.2 Published: JAN 23 2018 To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to 82 K Europeans via the exome chip, and similar to 90% of low-frequency non-coding variants in similar to 44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.

Published
2017
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12. Genetic and environmental (physical fitness and sedentary activity) interaction effects on cardiometabolic risk factors in Mexican American children and adolescents

Author

Arya, Rector, primary, Farook, Vidya S., additional, Fowler, Sharon P., additional, Puppala, Sobha, additional, Chittoor, Geetha, additional, Resendez, Roy G., additional, Mummidi, Srinivas, additional, Vanamala, Jairam, additional, Almasy, Laura, additional, Curran, Joanne E., additional, Comuzzie, Anthony G., additional, Lehman, Donna M., additional, Jenkinson, Christopher P., additional, Lynch, Jane L., additional, DeFronzo, Ralph A., additional, Blangero, John, additional, Hale, Daniel E., additional, Duggirala, Ravindranath, additional, and Diego, Vincent P., additional

Published
2018
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13. Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

Author

Flannick, Jason, primary, Fuchsberger, Christian, additional, Mahajan, Anubha, additional, Teslovich, Tanya M., additional, Agarwala, Vineeta, additional, Gaulton, Kyle J., additional, Caulkins, Lizz, additional, Koesterer, Ryan, additional, Ma, Clement, additional, Moutsianas, Loukas, additional, McCarthy, Davis J., additional, Rivas, Manuel A., additional, Perry, John R. B., additional, Sim, Xueling, additional, Blackwell, Thomas W., additional, Robertson, Neil R., additional, Rayner, N William, additional, Cingolani, Pablo, additional, Locke, Adam E., additional, Tajes, Juan Fernandez, additional, Highland, Heather M., additional, Dupuis, Josee, additional, Chines, Peter S., additional, Lindgren, Cecilia M., additional, Hartl, Christopher, additional, Jackson, Anne U., additional, Chen, Han, additional, Huyghe, Jeroen R., additional, van de Bunt, Martijn, additional, Pearson, Richard D., additional, Kumar, Ashish, additional, Müller-Nurasyid, Martina, additional, Grarup, Niels, additional, Stringham, Heather M., additional, Gamazon, Eric R., additional, Lee, Jaehoon, additional, Chen, Yuhui, additional, Scott, Robert A., additional, Below, Jennifer E., additional, Chen, Peng, additional, Huang, Jinyan, additional, Go, Min Jin, additional, Stitzel, Michael L., additional, Pasko, Dorota, additional, Parker, Stephen C. J., additional, Varga, Tibor V., additional, Green, Todd, additional, Beer, Nicola L., additional, Day-Williams, Aaron G., additional, Ferreira, Teresa, additional, Fingerlin, Tasha, additional, Horikoshi, Momoko, additional, Hu, Cheng, additional, Huh, Iksoo, additional, Ikram, Mohammad Kamran, additional, Kim, Bong-Jo, additional, Kim, Yongkang, additional, Kim, Young Jin, additional, Kwon, Min-Seok, additional, Lee, Juyoung, additional, Lee, Selyeong, additional, Lin, Keng-Han, additional, Maxwell, Taylor J., additional, Nagai, Yoshihiko, additional, Wang, Xu, additional, Welch, Ryan P, additional, Yoon, Joon, additional, Zhang, Weihua, additional, Barzilai, Nir, additional, Voight, Benjamin F., additional, Han, Bok-Ghee, additional, Jenkinson, Christopher P., additional, Kuulasmaa, Teemu, additional, Kuusisto, Johanna, additional, Manning, Alisa, additional, Ng, Maggie C. Y., additional, Palmer, Nicholette D., additional, Balkau, Beverley, additional, Stančáková, Alena, additional, Abboud, Hanna E., additional, Boeing, Heiner, additional, Giedraitis, Vilmantas, additional, Prabhakaran, Dorairaj, additional, Gottesman, Omri, additional, Scott, James, additional, Carey, Jason, additional, Kwan, Phoenix, additional, Grant, George, additional, Smith, Joshua D., additional, Neale, Benjamin M., additional, Purcell, Shaun, additional, Butterworth, Adam S., additional, Howson, Joanna M. M., additional, Lee, Heung Man, additional, Lu, Yingchang, additional, Kwak, Soo-Heon, additional, Zhao, Wei, additional, Danesh, John, additional, Lam, Vincent K. L., additional, Park, Kyong Soo, additional, Saleheen, Danish, additional, So, Wing Yee, additional, Tam, Claudia H. T., additional, Afzal, Uzma, additional, Aguilar, David, additional, Arya, Rector, additional, Aung, Tin, additional, Chan, Edmund, additional, Navarro, Carmen, additional, Cheng, Ching-Yu, additional, Palli, Domenico, additional, Correa, Adolfo, additional, Curran, Joanne E., additional, Rybin, Dennis, additional, Farook, Vidya S., additional, Fowler, Sharon P., additional, Freedman, Barry I., additional, Griswold, Michael, additional, Hale, Daniel Esten, additional, Hicks, Pamela J., additional, Khor, Chiea-Chuen, additional, Kumar, Satish, additional, Lehne, Benjamin, additional, Thuillier, Dorothée, additional, Lim, Wei Yen, additional, Liu, Jianjun, additional, Loh, Marie, additional, Musani, Solomon K., additional, Puppala, Sobha, additional, Scott, William R., additional, Yengo, Loïc, additional, Tan, Sian-Tsung, additional, Taylor, Herman A., additional, Thameem, Farook, additional, Wilson, Gregory, additional, Wong, Tien Yin, additional, Njølstad, Pål Rasmus, additional, Levy, Jonathan C., additional, Mangino, Massimo, additional, Bonnycastle, Lori L., additional, Schwarzmayr, Thomas, additional, Fadista, João, additional, Surdulescu, Gabriela L., additional, Herder, Christian, additional, Groves, Christopher J., additional, Wieland, Thomas, additional, Bork-Jensen, Jette, additional, Brandslund, Ivan, additional, Christensen, Cramer, additional, Koistinen, Heikki A., additional, Doney, Alex S .F., additional, Kinnunen, Leena, additional, Esko, Tõnu, additional, Farmer, Andrew J., additional, Hakaste, Liisa, additional, Hodgkiss, Dylan, additional, Kravic, Jasmina, additional, Lyssenko, Valeri, additional, Hollensted, Mette, additional, Jørgensen, Marit E., additional, Jørgensen, Torben, additional, Ladenvall, Claes, additional, Justesen, Johanne Marie, additional, Käräjämäki, Annemari, additional, Kriebel, Jennifer, additional, Rathmann, Wolfgang, additional, Lannfelt, Lars, additional, Lauritzen, Torsten, additional, Narisu, Narisu, additional, Linneberg, Allan, additional, Melander, Olle, additional, Milani, Lili, additional, Neville, Matt, additional, Orho-Melander, Marju, additional, Qi, Lu, additional, Qi, Qibin, additional, Roden, Michael, additional, Rolandsson, Olov, additional, Swift, Amy, additional, Rosengren, Anders H., additional, Stirrups, Kathleen, additional, Wood, Andrew R., additional, Mihailov, Evelin, additional, Blancher, Christine, additional, Carneiro, Mauricio O., additional, Maguire, Jared, additional, Poplin, Ryan, additional, Shakir, Khalid, additional, Fennell, Timothy, additional, DePristo, Mark, additional, de Angelis, Martin Hrabé, additional, Deloukas, Panos, additional, Gjesing, Anette P., additional, Jun, Goo, additional, Nilsson, Peter, additional, Murphy, Jacquelyn, additional, Onofrio, Robert, additional, Thorand, Barbara, additional, Hansen, Torben, additional, Meisinger, Christa, additional, Hu, Frank B., additional, Isomaa, Bo, additional, Karpe, Fredrik, additional, Liang, Liming, additional, Peters, Annette, additional, Huth, Cornelia, additional, O'Rahilly, Stephen P., additional, Palmer, Colin N. A., additional, Pedersen, Oluf, additional, Rauramaa, Rainer, additional, Tuomilehto, Jaakko, additional, Salomaa, Veikko, additional, Watanabe, Richard M., additional, Syvänen, Ann-Christine, additional, Bergman, Richard N., additional, Bharadwaj, Dwaipayan, additional, Bottinger, Erwin P., additional, Cho, Yoon Shin, additional, Chandak, Giriraj R., additional, Chan, Juliana C. N., additional, Chia, Kee Seng, additional, Daly, Mark J., additional, Ebrahim, Shah B., additional, Langenberg, Claudia, additional, Elliott, Paul, additional, Jablonski, Kathleen A., additional, Lehman, Donna M., additional, Jia, Weiping, additional, Ma, Ronald C. W., additional, Pollin, Toni I., additional, Sandhu, Manjinder, additional, Tandon, Nikhil, additional, Froguel, Philippe, additional, Barroso, Inês, additional, Teo, Yik Ying, additional, Zeggini, Eleftheria, additional, Loos, Ruth J. F., additional, Small, Kerrin S, additional, Ried, Janina S., additional, DeFronzo, Ralph A., additional, Grallert, Harald, additional, Glaser, Benjamin, additional, Metspalu, Andres, additional, Wareham, Nicholas J., additional, Walker, Mark, additional, Banks, Eric, additional, Gieger, Christian, additional, Ingelsson, Erik, additional, Im, Hae Kyung, additional, Illig, Thomas, additional, Franks, Paul W., additional, Buck, Gemma, additional, Trakalo, Joseph, additional, Buck, David, additional, Prokopenko, Inga, additional, Mägi, Reedik, additional, Lind, Lars, additional, Farjoun, Yossi, additional, Owen, Katharine R., additional, Gloyn, Anna L., additional, Strauch, Konstantin, additional, Tuomi, Tiinamaija, additional, Kooner, Jaspal Singh, additional, Lee, Jong-Young, additional, Park, Taesung, additional, Donnelly, Peter, additional, Morris, Andrew D., additional, Hattersley, Andrew T., additional, Bowden, Donald W., additional, Collins, Francis S., additional, Atzmon, Gil, additional, Chambers, John C., additional, Spector, Timothy D., additional, Laakso, Markku, additional, Strom, Tim M., additional, Bell, Graeme I., additional, Blangero, John, additional, Duggirala, Ravindranath, additional, Tai, E Shyong, additional, McVean, Gilean, additional, Hanis, Craig L., additional, Wilson, James G., additional, Seielstad, Mark, additional, Frayling, Timothy M., additional, Meigs, James B., additional, Cox, Nancy J., additional, Sladek, Rob, additional, Lander, Eric S., additional, Gabriel, Stacey, additional, Mohlke, Karen L., additional, Meitinger, Thomas, additional, Groop, Leif, additional, Abecasis, Goncalo, additional, Scott, Laura J., additional, Morris, Andrew P., additional, Kang, Hyun Min, additional, Altshuler, David, additional, Burtt, Noël P., additional, Florez, Jose C., additional, Boehnke, Michael, additional, and McCarthy, Mark I., additional

Published
2018
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14. Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

Author

Flannick, Jason, primary, Fuchsberger, Christian, additional, Mahajan, Anubha, additional, Teslovich, Tanya M., additional, Agarwala, Vineeta, additional, Gaulton, Kyle J., additional, Caulkins, Lizz, additional, Koesterer, Ryan, additional, Ma, Clement, additional, Moutsianas, Loukas, additional, McCarthy, Davis J., additional, Rivas, Manuel A., additional, Perry, John R. B., additional, Sim, Xueling, additional, Blackwell, Thomas W., additional, Robertson, Neil R., additional, Rayner, N William, additional, Cingolani, Pablo, additional, Locke, Adam E., additional, Tajes, Juan Fernandez, additional, Highland, Heather M., additional, Dupuis, Josee, additional, Chines, Peter S., additional, Lindgren, Cecilia M., additional, Hartl, Christopher, additional, Jackson, Anne U., additional, Chen, Han, additional, Huyghe, Jeroen R., additional, van de Bunt, Martijn, additional, Pearson, Richard D., additional, Kumar, Ashish, additional, Müller-Nurasyid, Martina, additional, Grarup, Niels, additional, Stringham, Heather M., additional, Gamazon, Eric R., additional, Lee, Jaehoon, additional, Chen, Yuhui, additional, Scott, Robert A., additional, Below, Jennifer E., additional, Chen, Peng, additional, Huang, Jinyan, additional, Go, Min Jin, additional, Stitzel, Michael L., additional, Pasko, Dorota, additional, Parker, Stephen C. J., additional, Varga, Tibor V., additional, Green, Todd, additional, Beer, Nicola L., additional, Day-Williams, Aaron G., additional, Ferreira, Teresa, additional, Fingerlin, Tasha, additional, Horikoshi, Momoko, additional, Hu, Cheng, additional, Huh, Iksoo, additional, Ikram, Mohammad Kamran, additional, Kim, Bong-Jo, additional, Kim, Yongkang, additional, Kim, Young Jin, additional, Kwon, Min-Seok, additional, Lee, Juyoung, additional, Lee, Selyeong, additional, Lin, Keng-Han, additional, Maxwell, Taylor J., additional, Nagai, Yoshihiko, additional, Wang, Xu, additional, Welch, Ryan P., additional, Yoon, Joon, additional, Zhang, Weihua, additional, Barzilai, Nir, additional, Voight, Benjamin F., additional, Han, Bok-Ghee, additional, Jenkinson, Christopher P., additional, Kuulasmaa, Teemu, additional, Kuusisto, Johanna, additional, Manning, Alisa, additional, Ng, Maggie C. Y., additional, Palmer, Nicholette D., additional, Balkau, Beverley, additional, Stančáková, Alena, additional, Abboud, Hanna E., additional, Boeing, Heiner, additional, Giedraitis, Vilmantas, additional, Prabhakaran, Dorairaj, additional, Gottesman, Omri, additional, Scott, James, additional, Carey, Jason, additional, Kwan, Phoenix, additional, Grant, George, additional, Smith, Joshua D., additional, Neale, Benjamin M., additional, Purcell, Shaun, additional, Butterworth, Adam S., additional, Howson, Joanna M. M., additional, Lee, Heung Man, additional, Lu, Yingchang, additional, Kwak, Soo-Heon, additional, Zhao, Wei, additional, Danesh, John, additional, Lam, Vincent K. L., additional, Park, Kyong Soo, additional, Saleheen, Danish, additional, So, Wing Yee, additional, Tam, Claudia H. T., additional, Afzal, Uzma, additional, Aguilar, David, additional, Arya, Rector, additional, Aung, Tin, additional, Chan, Edmund, additional, Navarro, Carmen, additional, Cheng, Ching-Yu, additional, Palli, Domenico, additional, Correa, Adolfo, additional, Curran, Joanne E., additional, Rybin, Dennis, additional, Farook, Vidya S., additional, Fowler, Sharon P., additional, Freedman, Barry I., additional, Griswold, Michael, additional, Hale, Daniel Esten, additional, Hicks, Pamela J., additional, Khor, Chiea-Chuen, additional, Kumar, Satish, additional, Lehne, Benjamin, additional, Thuillier, Dorothée, additional, Lim, Wei Yen, additional, Liu, Jianjun, additional, Loh, Marie, additional, Musani, Solomon K., additional, Puppala, Sobha, additional, Scott, William R., additional, Yengo, Loïc, additional, Tan, Sian-Tsung, additional, Taylor, Herman A., additional, Thameem, Farook, additional, Wilson, Gregory, additional, Wong, Tien Yin, additional, Njølstad, Pål Rasmus, additional, Levy, Jonathan C., additional, Mangino, Massimo, additional, Bonnycastle, Lori L., additional, Schwarzmayr, Thomas, additional, Fadista, João, additional, Surdulescu, Gabriela L., additional, Herder, Christian, additional, Groves, Christopher J., additional, Wieland, Thomas, additional, Bork-Jensen, Jette, additional, Brandslund, Ivan, additional, Christensen, Cramer, additional, Koistinen, Heikki A., additional, Doney, Alex S. F., additional, Kinnunen, Leena, additional, Esko, Tõnu, additional, Farmer, Andrew J., additional, Hakaste, Liisa, additional, Hodgkiss, Dylan, additional, Kravic, Jasmina, additional, Lyssenko, Valeri, additional, Hollensted, Mette, additional, Jørgensen, Marit E., additional, Jørgensen, Torben, additional, Ladenvall, Claes, additional, Justesen, Johanne Marie, additional, Käräjämäki, Annemari, additional, Kriebel, Jennifer, additional, Rathmann, Wolfgang, additional, Lannfelt, Lars, additional, Lauritzen, Torsten, additional, Narisu, Narisu, additional, Linneberg, Allan, additional, Melander, Olle, additional, Milani, Lili, additional, Neville, Matt, additional, Orho-Melander, Marju, additional, Qi, Lu, additional, Qi, Qibin, additional, Roden, Michael, additional, Rolandsson, Olov, additional, Swift, Amy, additional, Rosengren, Anders H., additional, Stirrups, Kathleen, additional, Wood, Andrew R., additional, Mihailov, Evelin, additional, Blancher, Christine, additional, Carneiro, Mauricio O., additional, Maguire, Jared, additional, Poplin, Ryan, additional, Shakir, Khalid, additional, Fennell, Timothy, additional, DePristo, Mark, additional, de Angelis, Martin Hrabé, additional, Deloukas, Panos, additional, Gjesing, Anette P., additional, Jun, Goo, additional, Nilsson, Peter, additional, Murphy, Jacquelyn, additional, Onofrio, Robert, additional, Thorand, Barbara, additional, Hansen, Torben, additional, Meisinger, Christa, additional, Hu, Frank B., additional, Isomaa, Bo, additional, Karpe, Fredrik, additional, Liang, Liming, additional, Peters, Annette, additional, Huth, Cornelia, additional, O'Rahilly, Stephen P, additional, Palmer, Colin N. A., additional, Pedersen, Oluf, additional, Rauramaa, Rainer, additional, Tuomilehto, Jaakko, additional, Salomaa, Veikko, additional, Watanabe, Richard M., additional, Syvänen, Ann-Christine, additional, Bergman, Richard N., additional, Bharadwaj, Dwaipayan, additional, Bottinger, Erwin P., additional, Cho, Yoon Shin, additional, Chandak, Giriraj R., additional, Chan, Juliana CN, additional, Chia, Kee Seng, additional, Daly, Mark J., additional, Ebrahim, Shah B., additional, Langenberg, Claudia, additional, Elliott, Paul, additional, Jablonski, Kathleen A., additional, Lehman, Donna M., additional, Jia, Weiping, additional, Ma, Ronald C. W., additional, Pollin, Toni I., additional, Sandhu, Manjinder, additional, Tandon, Nikhil, additional, Froguel, Philippe, additional, Barroso, Inês, additional, Teo, Yik Ying, additional, Zeggini, Eleftheria, additional, Loos, Ruth J. F., additional, Small, Kerrin S., additional, Ried, Janina S., additional, DeFronzo, Ralph A., additional, Grallert, Harald, additional, Glaser, Benjamin, additional, Metspalu, Andres, additional, Wareham, Nicholas J., additional, Walker, Mark, additional, Banks, Eric, additional, Gieger, Christian, additional, Ingelsson, Erik, additional, Im, Hae Kyung, additional, Illig, Thomas, additional, Franks, Paul W., additional, Buck, Gemma, additional, Trakalo, Joseph, additional, Buck, David, additional, Prokopenko, Inga, additional, Mägi, Reedik, additional, Lind, Lars, additional, Farjoun, Yossi, additional, Owen, Katharine R., additional, Gloyn, Anna L., additional, Strauch, Konstantin, additional, Tuomi, Tiinamaija, additional, Kooner, Jaspal Singh, additional, Lee, Jong-Young, additional, Park, Taesung, additional, Donnelly, Peter, additional, Morris, Andrew D., additional, Hattersley, Andrew T., additional, Bowden, Donald W., additional, Collins, Francis S., additional, Atzmon, Gil, additional, Chambers, John C., additional, Spector, Timothy D., additional, Laakso, Markku, additional, Strom, Tim M., additional, Bell, Graeme I., additional, Blangero, John, additional, Duggirala, Ravindranath, additional, Tai, E. Shyong, additional, McVean, Gilean, additional, Hanis, Craig L., additional, Wilson, James G., additional, Seielstad, Mark, additional, Frayling, Timothy M., additional, Meigs, James B., additional, Cox, Nancy J., additional, Sladek, Rob, additional, Lander, Eric S., additional, Gabriel, Stacey, additional, Mohlke, Karen L., additional, Meitinger, Thomas, additional, Groop, Leif, additional, Abecasis, Goncalo, additional, Scott, Laura J., additional, Morris, Andrew P., additional, Kang, Hyun Min, additional, Altshuler, David, additional, Burtt, Noël P., additional, Florez, Jose C., additional, Boehnke, Michael, additional, and McCarthy, Mark I., additional

Published
2017
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15. A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk

Author

Manning, Alisa, primary, Highland, Heather M., additional, Gasser, Jessica, additional, Sim, Xueling, additional, Tukiainen, Taru, additional, Fontanillas, Pierre, additional, Grarup, Niels, additional, Rivas, Manuel A., additional, Mahajan, Anubha, additional, Locke, Adam E., additional, Cingolani, Pablo, additional, Pers, Tune H., additional, Viñuela, Ana, additional, Brown, Andrew A., additional, Wu, Ying, additional, Flannick, Jason, additional, Fuchsberger, Christian, additional, Gamazon, Eric R., additional, Gaulton, Kyle J., additional, Im, Hae Kyung, additional, Teslovich, Tanya M., additional, Blackwell, Thomas W., additional, Bork-Jensen, Jette, additional, Burtt, Noël P., additional, Chen, Yuhui, additional, Green, Todd, additional, Hartl, Christopher, additional, Kang, Hyun Min, additional, Kumar, Ashish, additional, Ladenvall, Claes, additional, Ma, Clement, additional, Moutsianas, Loukas, additional, Pearson, Richard D., additional, Perry, John R.B., additional, Rayner, N. William, additional, Robertson, Neil R., additional, Scott, Laura J., additional, van de Bunt, Martijn, additional, Eriksson, Johan G., additional, Jula, Antti, additional, Koskinen, Seppo, additional, Lehtimäki, Terho, additional, Palotie, Aarno, additional, Raitakari, Olli T., additional, Jacobs, Suzanne B.R., additional, Wessel, Jennifer, additional, Chu, Audrey Y., additional, Scott, Robert A., additional, Goodarzi, Mark O., additional, Blancher, Christine, additional, Buck, Gemma, additional, Buck, David, additional, Chines, Peter S., additional, Gabriel, Stacey, additional, Gjesing, Anette P., additional, Groves, Christopher J., additional, Hollensted, Mette, additional, Huyghe, Jeroen R., additional, Jackson, Anne U., additional, Jun, Goo, additional, Justesen, Johanne Marie, additional, Mangino, Massimo, additional, Murphy, Jacquelyn, additional, Neville, Matt, additional, Onofrio, Robert, additional, Small, Kerrin S., additional, Stringham, Heather M., additional, Trakalo, Joseph, additional, Banks, Eric, additional, Carey, Jason, additional, Carneiro, Mauricio O., additional, DePristo, Mark, additional, Farjoun, Yossi, additional, Fennell, Timothy, additional, Goldstein, Jacqueline I., additional, Grant, George, additional, Hrabé de Angelis, Martin, additional, Maguire, Jared, additional, Neale, Benjamin M., additional, Poplin, Ryan, additional, Purcell, Shaun, additional, Schwarzmayr, Thomas, additional, Shakir, Khalid, additional, Smith, Joshua D., additional, Strom, Tim M., additional, Wieland, Thomas, additional, Lindstrom, Jaana, additional, Brandslund, Ivan, additional, Christensen, Cramer, additional, Surdulescu, Gabriela L., additional, Lakka, Timo A., additional, Doney, Alex S.F., additional, Nilsson, Peter, additional, Wareham, Nicholas J., additional, Langenberg, Claudia, additional, Varga, Tibor V., additional, Franks, Paul W., additional, Rolandsson, Olov, additional, Rosengren, Anders H., additional, Farook, Vidya S., additional, Thameem, Farook, additional, Puppala, Sobha, additional, Kumar, Satish, additional, Lehman, Donna M., additional, Jenkinson, Christopher P., additional, Curran, Joanne E., additional, Hale, Daniel Esten, additional, Fowler, Sharon P., additional, Arya, Rector, additional, DeFronzo, Ralph A., additional, Abboud, Hanna E., additional, Syvänen, Ann-Christine, additional, Hicks, Pamela J., additional, Palmer, Nicholette D., additional, Ng, Maggie C.Y., additional, Bowden, Donald W., additional, Freedman, Barry I., additional, Esko, Tõnu, additional, Mägi, Reedik, additional, Milani, Lili, additional, Mihailov, Evelin, additional, Metspalu, Andres, additional, Narisu, Narisu, additional, Kinnunen, Leena, additional, Bonnycastle, Lori L., additional, Swift, Amy, additional, Pasko, Dorota, additional, Wood, Andrew R., additional, Fadista, João, additional, Pollin, Toni I., additional, Barzilai, Nir, additional, Atzmon, Gil, additional, Glaser, Benjamin, additional, Thorand, Barbara, additional, Strauch, Konstantin, additional, Peters, Annette, additional, Roden, Michael, additional, Müller-Nurasyid, Martina, additional, Liang, Liming, additional, Kriebel, Jennifer, additional, Illig, Thomas, additional, Grallert, Harald, additional, Gieger, Christian, additional, Meisinger, Christa, additional, Lannfelt, Lars, additional, Musani, Solomon K., additional, Griswold, Michael, additional, Taylor, Herman A., additional, Wilson, Gregory, additional, Correa, Adolfo, additional, Oksa, Heikki, additional, Scott, William R., additional, Afzal, Uzma, additional, Tan, Sian-Tsung, additional, Loh, Marie, additional, Chambers, John C., additional, Sehmi, Jobanpreet, additional, Kooner, Jaspal Singh, additional, Lehne, Benjamin, additional, Cho, Yoon Shin, additional, Lee, Jong-Young, additional, Han, Bok-Ghee, additional, Käräjämäki, Annemari, additional, Qi, Qibin, additional, Qi, Lu, additional, Huang, Jinyan, additional, Hu, Frank B., additional, Melander, Olle, additional, Orho-Melander, Marju, additional, Below, Jennifer E., additional, Aguilar, David, additional, Wong, Tien Yin, additional, Liu, Jianjun, additional, Khor, Chiea-Chuen, additional, Chia, Kee Seng, additional, Lim, Wei Yen, additional, Cheng, Ching-Yu, additional, Chan, Edmund, additional, Tai, E Shyong, additional, Aung, Tin, additional, Linneberg, Allan, additional, Isomaa, Bo, additional, Meitinger, Thomas, additional, Tuomi, Tiinamaija, additional, Hakaste, Liisa, additional, Kravic, Jasmina, additional, Jørgensen, Marit E., additional, Lauritzen, Torsten, additional, Deloukas, Panos, additional, Stirrups, Kathleen E., additional, Owen, Katharine R., additional, Farmer, Andrew J., additional, Frayling, Timothy M., additional, O'Rahilly, Stephen P., additional, Walker, Mark, additional, Levy, Jonathan C., additional, Hodgkiss, Dylan, additional, Hattersley, Andrew T., additional, Kuulasmaa, Teemu, additional, Stančáková, Alena, additional, Barroso, Inês, additional, Bharadwaj, Dwaipayan, additional, Chan, Juliana, additional, Chandak, Giriraj R., additional, Daly, Mark J., additional, Donnelly, Peter J., additional, Ebrahim, Shah B., additional, Elliott, Paul, additional, Fingerlin, Tasha, additional, Froguel, Philippe, additional, Hu, Cheng, additional, Jia, Weiping, additional, Ma, Ronald C.W., additional, McVean, Gilean, additional, Park, Taesung, additional, Prabhakaran, Dorairaj, additional, Sandhu, Manjinder, additional, Scott, James, additional, Sladek, Rob, additional, Tandon, Nikhil, additional, Teo, Yik Ying, additional, Zeggini, Eleftheria, additional, Watanabe, Richard M., additional, Koistinen, Heikki A., additional, Kesaniemi, Y. Antero, additional, Uusitupa, Matti, additional, Spector, Timothy D., additional, Salomaa, Veikko, additional, Rauramaa, Rainer, additional, Palmer, Colin N.A., additional, Prokopenko, Inga, additional, Morris, Andrew D., additional, Bergman, Richard N., additional, Collins, Francis S., additional, Lind, Lars, additional, Ingelsson, Erik, additional, Tuomilehto, Jaakko, additional, Karpe, Fredrik, additional, Groop, Leif, additional, Jørgensen, Torben, additional, Hansen, Torben, additional, Pedersen, Oluf, additional, Kuusisto, Johanna, additional, Abecasis, Gonçalo, additional, Bell, Graeme I., additional, Blangero, John, additional, Cox, Nancy J., additional, Duggirala, Ravindranath, additional, Seielstad, Mark, additional, Wilson, James G., additional, Dupuis, Josee, additional, Ripatti, Samuli, additional, Hanis, Craig L., additional, Florez, Jose C., additional, Mohlke, Karen L., additional, Meigs, James B., additional, Laakso, Markku, additional, Morris, Andrew P., additional, Boehnke, Michael, additional, Altshuler, David, additional, McCarthy, Mark I., additional, Gloyn, Anna L., additional, and Lindgren, Cecilia M., additional

Published
2017
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16. A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk

Author

Manning, Alisa, Highland, Heather M., Gasser, Jessica, Sim, Xueling, Tukiainen, Taru, Fontanillas, Pierre, Grarup, Niels, Rivas, Manuel A., Mahajan, Anubha, Locke, Adam E., Cingolani, Pablo, Pers, Tune H., Vinuela, Ana, Brown, Andrew A., Wu, Ying, Flannick, Jason, Fuchsberger, Christian, Gamazon, Eric R., Gaulton, Kyle J., Im, Hae Kyung, Teslovich, Tanya M., Blackwell, Thomas W., Bork-Jensen, Jette, Burtt, Noel P., Chen, Yuhui, Green, Todd, Hartl, Christopher, Kang, Hyun Min, Kumar, Ashish, Ladenvall, Claes, Ma, Clement, Moutsianas, Loukas, Pearson, Richard D., Perry, John R. B., Rayner, N. William, Robertson, Neil R., Scott, Laura J., van de Bunt, Martijn, Eriksson, Johan G., Jula, Antti, Koskinen, Seppo, Lehtimaki, Terho, Palotie, Aarno, Raitakari, Olli T., Jacobs, Suzanne B. R., Wessel, Jennifer, Chu, Audrey Y., Scott, Robert A., Goodarzi, Mark O., Blancher, Christine, Buck, Gemma, Buck, David, Chines, Peter S., Gabriel, Stacey, Gjesing, Anette P., Groves, Christopher J., Hollensted, Mette, Huyghe, Jeroen R., Jackson, Anne U., Jun, Goo, Justesen, Johanne Marie, Mangino, Massimo, Murphy, Jacquelyn, Neville, Matt, Onofrio, Robert, Small, Kerrin S., Stringham, Heather M., Trakalo, Joseph, Banks, Eric, Carey, Jason, Carneiro, Mauricio O., DePristo, Mark, Farjoun, Yossi, Fennell, Timothy, Goldstein, Jacqueline I., Grant, George, de Angelis, Martin Hrabe, Maguire, Jared, Neale, Benjamin M., Poplin, Ryan, Purcell, Shaun, Schwarzmayr, Thomas, Shakir, Khalid, Smith, Joshua D., Strom, Tim M., Wieland, Thomas, Lindstrom, Jaana, Brandslund, Ivan, Christensen, Cramer, Surdulescu, Gabriela L., Lakka, Timo A., Doney, Alex S. F., Nilsson, Peter, Wareham, Nicholas J., Langenberg, Claudia, Varga, Tibor V., Franks, Paul W., Rolandsson, Olov, Rosengren, Anders H., Farook, Vidya S., Thameem, Farook, Puppala, Sobha, Kumar, Satish, Lehman, Donna M., Jenkinson, Christopher P., Curran, Joanne E., Hale, Daniel Esten, Fowler, Sharon P., Arya, Rector, DeFronzo, Ralph A., Abboud, Hanna E., Syvanen, Ann-Christine, Hicks, Pamela J., Palmer, Nicholette D., Ng, Maggie C. Y., Bowden, Donald W., Freedman, Barry I., Esko, Tonu, Magi, Reedik, Milani, Lili, Mihailov, Evelin, Metspalu, Andres, Narisu, Narisu, Kinnunen, Leena, Bonnycastle, Lori L., Swift, Amy, Pasko, Dorota, Wood, Andrew R., Fadista, Joao, Pollin, Toni I., Barzilai, Nir, Atzmon, Gil, Glaser, Benjamin, Thorand, Barbara, Strauch, Konstantin, Peters, Annette, Roden, Michael, Mueller-Nurasyid, Martina, Liang, Liming, Kriebel, Jennifer, Illig, Thomas, Grallert, Harald, Gieger, Christian, Meisinger, Christa, Lannfelt, Lars, Musani, Solomon K., Griswold, Michael, Taylor, Herman A., Jr., Wilson, Gregory, Sr., Correa, Adolfo, Oksa, Heikki, Scott, William R., Afzal, Uzma, Tan, Sian-Tsung, Loh, Marie, Chambers, John C., Sehmi, Jobanpreet, Kooner, Jaspal Singh, Lehne, Benjamin, Cho, Yoon Shin, Lee, Jong-Young, Han, Bok-Ghee, Karajamaki, Annemari, Qi, Qibin, Qi, Lu, Huang, Jinyan, Hu, Frank B., Melander, Olle, Orho-Melander, Marju, Below, Jennifer E., Aguilar, David, Wong, Tien Yin, Liu, Jianjun, Khor, Chiea-Chuen, Chia, Kee Seng, Lim, Wei Yen, Cheng, Ching-Yu, Chan, Edmund, Tai, E. Shyong, Aung, Tin, Linneberg, Allan, Isomaa, Bo, Meitinger, Thomas, Tuomi, Tiinamaija, Hakaste, Liisa, Kravic, Jasmina, Jorgensen, Marit E., Lauritzen, Torsten, Deloukas, Panos, Stirrups, Kathleen E., Owen, Katharine R., Farmer, Andrew J., Frayling, Timothy M., O'Rahilly, Stephen P., Walker, Mark, Levy, Jonathan C., Hodgkiss, Dylan, Hattersley, Andrew T., Kuulasmaa, Teemu, Stancakova, Alena, Barroso, Ines, Bharadwaj, Dwaipayan, Chan, Juliana, Chandak, Giriraj R., Daly, Mark J., Donnelly, Peter J., Ebrahim, Shah B., Elliott, Paul, Fingerlin, Tasha, Froguel, Philippe, Hu, Cheng, Jia, Weiping, Ma, Ronald C. W., McVean, Gilean, Park, Taesung, Prabhakaran, Dorairaj, Sandhu, Manjinder, Scott, James, Sladek, Rob, Tandon, Nikhil, Teo, Yik Ying, Zeggini, Eleftheria, Watanabe, Richard M., Koistinen, Heikki A., Kesaniemi, Y. Antero, Uusitupa, Matti, Spector, Timothy D., Salomaa, Veikko, Rauramaa, Rainer, Palmer, Colin N. A., Prokopenko, Inga, Morris, Andrew D., Bergman, Richard N., Collins, Francis S., Lind, Lars, Ingelsson, Erik, Tuomilehto, Jaakko, Karpe, Fredrik, Groop, Leif, Jorgensen, Torben, Hansen, Torben, Pedersen, Oluf, Kuusisto, Johanna, Abecasis, GonOalo, Bell, Graeme I., Blangero, John, Cox, Nancy J., Duggirala, Ravindranath, Seielstad, Mark, Wilson, James G., Dupuis, Josee, Ripatti, Samuli, Hanis, Craig L., Florez, Jose C., Mohlke, Karen L., Meigs, James B., Laakso, Markku, Morris, Andrew P., Boehnke, Michael, Altshuler, David, McCarthy, Mark I., Gloyn, Anna L., Lindgren, Cecilia M., Manning, Alisa, Highland, Heather M., Gasser, Jessica, Sim, Xueling, Tukiainen, Taru, Fontanillas, Pierre, Grarup, Niels, Rivas, Manuel A., Mahajan, Anubha, Locke, Adam E., Cingolani, Pablo, Pers, Tune H., Vinuela, Ana, Brown, Andrew A., Wu, Ying, Flannick, Jason, Fuchsberger, Christian, Gamazon, Eric R., Gaulton, Kyle J., Im, Hae Kyung, Teslovich, Tanya M., Blackwell, Thomas W., Bork-Jensen, Jette, Burtt, Noel P., Chen, Yuhui, Green, Todd, Hartl, Christopher, Kang, Hyun Min, Kumar, Ashish, Ladenvall, Claes, Ma, Clement, Moutsianas, Loukas, Pearson, Richard D., Perry, John R. B., Rayner, N. William, Robertson, Neil R., Scott, Laura J., van de Bunt, Martijn, Eriksson, Johan G., Jula, Antti, Koskinen, Seppo, Lehtimaki, Terho, Palotie, Aarno, Raitakari, Olli T., Jacobs, Suzanne B. R., Wessel, Jennifer, Chu, Audrey Y., Scott, Robert A., Goodarzi, Mark O., Blancher, Christine, Buck, Gemma, Buck, David, Chines, Peter S., Gabriel, Stacey, Gjesing, Anette P., Groves, Christopher J., Hollensted, Mette, Huyghe, Jeroen R., Jackson, Anne U., Jun, Goo, Justesen, Johanne Marie, Mangino, Massimo, Murphy, Jacquelyn, Neville, Matt, Onofrio, Robert, Small, Kerrin S., Stringham, Heather M., Trakalo, Joseph, Banks, Eric, Carey, Jason, Carneiro, Mauricio O., DePristo, Mark, Farjoun, Yossi, Fennell, Timothy, Goldstein, Jacqueline I., Grant, George, de Angelis, Martin Hrabe, Maguire, Jared, Neale, Benjamin M., Poplin, Ryan, Purcell, Shaun, Schwarzmayr, Thomas, Shakir, Khalid, Smith, Joshua D., Strom, Tim M., Wieland, Thomas, Lindstrom, Jaana, Brandslund, Ivan, Christensen, Cramer, Surdulescu, Gabriela L., Lakka, Timo A., Doney, Alex S. F., Nilsson, Peter, Wareham, Nicholas J., Langenberg, Claudia, Varga, Tibor V., Franks, Paul W., Rolandsson, Olov, Rosengren, Anders H., Farook, Vidya S., Thameem, Farook, Puppala, Sobha, Kumar, Satish, Lehman, Donna M., Jenkinson, Christopher P., Curran, Joanne E., Hale, Daniel Esten, Fowler, Sharon P., Arya, Rector, DeFronzo, Ralph A., Abboud, Hanna E., Syvanen, Ann-Christine, Hicks, Pamela J., Palmer, Nicholette D., Ng, Maggie C. Y., Bowden, Donald W., Freedman, Barry I., Esko, Tonu, Magi, Reedik, Milani, Lili, Mihailov, Evelin, Metspalu, Andres, Narisu, Narisu, Kinnunen, Leena, Bonnycastle, Lori L., Swift, Amy, Pasko, Dorota, Wood, Andrew R., Fadista, Joao, Pollin, Toni I., Barzilai, Nir, Atzmon, Gil, Glaser, Benjamin, Thorand, Barbara, Strauch, Konstantin, Peters, Annette, Roden, Michael, Mueller-Nurasyid, Martina, Liang, Liming, Kriebel, Jennifer, Illig, Thomas, Grallert, Harald, Gieger, Christian, Meisinger, Christa, Lannfelt, Lars, Musani, Solomon K., Griswold, Michael, Taylor, Herman A., Jr., Wilson, Gregory, Sr., Correa, Adolfo, Oksa, Heikki, Scott, William R., Afzal, Uzma, Tan, Sian-Tsung, Loh, Marie, Chambers, John C., Sehmi, Jobanpreet, Kooner, Jaspal Singh, Lehne, Benjamin, Cho, Yoon Shin, Lee, Jong-Young, Han, Bok-Ghee, Karajamaki, Annemari, Qi, Qibin, Qi, Lu, Huang, Jinyan, Hu, Frank B., Melander, Olle, Orho-Melander, Marju, Below, Jennifer E., Aguilar, David, Wong, Tien Yin, Liu, Jianjun, Khor, Chiea-Chuen, Chia, Kee Seng, Lim, Wei Yen, Cheng, Ching-Yu, Chan, Edmund, Tai, E. Shyong, Aung, Tin, Linneberg, Allan, Isomaa, Bo, Meitinger, Thomas, Tuomi, Tiinamaija, Hakaste, Liisa, Kravic, Jasmina, Jorgensen, Marit E., Lauritzen, Torsten, Deloukas, Panos, Stirrups, Kathleen E., Owen, Katharine R., Farmer, Andrew J., Frayling, Timothy M., O'Rahilly, Stephen P., Walker, Mark, Levy, Jonathan C., Hodgkiss, Dylan, Hattersley, Andrew T., Kuulasmaa, Teemu, Stancakova, Alena, Barroso, Ines, Bharadwaj, Dwaipayan, Chan, Juliana, Chandak, Giriraj R., Daly, Mark J., Donnelly, Peter J., Ebrahim, Shah B., Elliott, Paul, Fingerlin, Tasha, Froguel, Philippe, Hu, Cheng, Jia, Weiping, Ma, Ronald C. W., McVean, Gilean, Park, Taesung, Prabhakaran, Dorairaj, Sandhu, Manjinder, Scott, James, Sladek, Rob, Tandon, Nikhil, Teo, Yik Ying, Zeggini, Eleftheria, Watanabe, Richard M., Koistinen, Heikki A., Kesaniemi, Y. Antero, Uusitupa, Matti, Spector, Timothy D., Salomaa, Veikko, Rauramaa, Rainer, Palmer, Colin N. A., Prokopenko, Inga, Morris, Andrew D., Bergman, Richard N., Collins, Francis S., Lind, Lars, Ingelsson, Erik, Tuomilehto, Jaakko, Karpe, Fredrik, Groop, Leif, Jorgensen, Torben, Hansen, Torben, Pedersen, Oluf, Kuusisto, Johanna, Abecasis, GonOalo, Bell, Graeme I., Blangero, John, Cox, Nancy J., Duggirala, Ravindranath, Seielstad, Mark, Wilson, James G., Dupuis, Josee, Ripatti, Samuli, Hanis, Craig L., Florez, Jose C., Mohlke, Karen L., Meigs, James B., Laakso, Markku, Morris, Andrew P., Boehnke, Michael, Altshuler, David, McCarthy, Mark I., Gloyn, Anna L., and Lindgren, Cecilia M.

Abstract

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.

Published
2017
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17. Data Descriptor:Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

Author

Flannick, Jason, Fuchsberger, Christian, Mahajan, Anubha, Teslovich, Tanya M., Agarwala, Vineeta, Gaulton, Kyle J., Caulkins, Lizz, Koesterer, Ryan, Ma, Clement, Moutsianas, Loukas, McCarthy, Davis J., Rivas, Manuel A., Perry, John R.B., Sim, Xueling, Blackwell, Thomas W., Robertson, Neil R., Rayner, N. William, Cingolani, Pablo, Locke, Adam E., Tajes, Juan Fernandez, Highland, Heather M., Dupuis, Josée, Chines, Peter S., Lindgren, Cecilia M., Hartl, Christopher, Jackson, Anne U., Chen, Han, Huyghe, Jeroen R., Van De Bunt, Martijn, Pearson, Richard D., Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M., Gamazon, Eric R., Lee, Jaehoon, Chen, Yuhui, Scott, Robert A., Below, Jennifer E., Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L., Pasko, Dorota, Parker, Stephen C.J., Varga, Tibor V., Green, Todd, Beer, Nicola L., Day-Williams, Aaron G., Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng Han, Maxwell, Taylor J., Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P., Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F., Han, Bok Ghee, Jenkinson, Christopher P., Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie C.Y., Palmer, Nicholette D., Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E., Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D., Neale, Benjamin M., Purcell, Shaun, Butterworth, Adam S., Howson, Joanna M.M., Lee, Heung Man, Lu, Yingchang, Kwak, Soo Heon, Zhao, Wei, Danesh, John, Lam, Vincent K.L., Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia H.T., Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E., Rybin, Dennis, Farook, Vidya S., Fowler, Sharon P., Freedman, Barry I., Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J., Khor, Chiea Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, Loh, Marie, Musani, Solomon K., Puppala, Sobha, Scott, William R., Yengo, Loïc, Tan, Sian Tsung, Taylor, Herman A., Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C., Mangino, Massimo, Bonnycastle, Lori L., Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L., Herder, Christian, Groves, Christopher J., Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A., Doney, Alex S.F., Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J., Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeriya, Hollensted, Mette, Jørgensen, Marit E., Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Swift, Amy, Rosengren, Anders H., Stirrups, Kathleen, Wood, Andrew R., Mihailov, Evelin, Blancher, Christine, Carneiro, Mauricio O., Maguire, Jared, Poplin, Ryan, Shakir, Khalid, Fennell, Timothy, DePristo, Mark, De Angelis, Martin Hrabé, Deloukas, Panos, Gjesing, Anette P., Jun, Goo, Nilsson, Peter M., Murphy, Jacquelyn, Onofrio, Robert, Thorand, Barbara, Hansen, Torben, Meisinger, Christa, Hu, Frank B., Isomaa, Bo, Karpe, Fredrik, Liang, Liming, Peters, Annette, Huth, Cornelia, O'Rahilly, Stephen P., Palmer, Colin N.A., Pedersen, Oluf, Rauramaa, Rainer, Tuomilehto, Jaakko, Salomaa, Veikko, Watanabe, Richard M., Syvänen, Ann Christine, Bergman, Richard N., Bharadwaj, Dwaipayan, Bottinger, Erwin P., Cho, Yoon Shin, Chandak, Giriraj R., Chan, Juliana C.N., Chia, Kee Seng, Daly, Mark J., Ebrahim, Shah B., Langenberg, Claudia, Elliott, Paul, Jablonski, Kathleen A., Lehman, Donna M., Jia, Weiping, Ma, Ronald C.W., Pollin, Toni I., Sandhu, Manjinder, Tandon, Nikhil, Froguel, Philippe, Barroso, Inês, Teo, Yik Ying, Zeggini, Eleftheria, Loos, Ruth J.F., Small, Kerrin S., Ried, Janina S., DeFronzo, Ralph A., Grallert, Harald, Glaser, Benjamin, Metspalu, Andres, Wareham, Nicholas J., Walker, Mark, Banks, Eric, Gieger, Christian, Ingelsson, Erik, Im, Hae Kyung, Illig, Thomas, Franks, Paul W., Buck, Gemma, Trakalo, Joseph, Buck, David, Prokopenko, Inga, Mägi, Reedik, Lind, Lars, Farjoun, Yossi, Owen, Katharine R., Gloyn, Anna L., Strauch, Konstantin, Tuomi, Tiinamaija, Kooner, Jaspal Singh, Lee, Jong Young, Park, Taesung, Donnelly, Peter, Morris, Andrew D., Hattersley, Andrew T., Bowden, Donald W., Collins, Francis S., Atzmon, Gil, Chambers, John C., Spector, Timothy D., Laakso, Markku, Strom, Tim M., Bell, Graeme I., Blangero, John, Duggirala, Ravindranath, Tai, Eshyong, McVean, Gilean, Hanis, Craig L., Wilson, James G., Seielstad, Mark, Frayling, Timothy M., Meigs, James B., Cox, Nancy J., Sladek, Rob, Lander, Eric S., Gabriel, Stacey, Mohlke, Karen L., Meitinger, Thomas, Groop, Leif, Abecasis, Goncalo, Scott, Laura J., Morris, Andrew P., Kang, Hyun Min, Altshuler, David, Burtt, Noël P., Florez, Jose C., Boehnke, Michael, McCarthy, Mark I., Flannick, Jason, Fuchsberger, Christian, Mahajan, Anubha, Teslovich, Tanya M., Agarwala, Vineeta, Gaulton, Kyle J., Caulkins, Lizz, Koesterer, Ryan, Ma, Clement, Moutsianas, Loukas, McCarthy, Davis J., Rivas, Manuel A., Perry, John R.B., Sim, Xueling, Blackwell, Thomas W., Robertson, Neil R., Rayner, N. William, Cingolani, Pablo, Locke, Adam E., Tajes, Juan Fernandez, Highland, Heather M., Dupuis, Josée, Chines, Peter S., Lindgren, Cecilia M., Hartl, Christopher, Jackson, Anne U., Chen, Han, Huyghe, Jeroen R., Van De Bunt, Martijn, Pearson, Richard D., Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M., Gamazon, Eric R., Lee, Jaehoon, Chen, Yuhui, Scott, Robert A., Below, Jennifer E., Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L., Pasko, Dorota, Parker, Stephen C.J., Varga, Tibor V., Green, Todd, Beer, Nicola L., Day-Williams, Aaron G., Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng Han, Maxwell, Taylor J., Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P., Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F., Han, Bok Ghee, Jenkinson, Christopher P., Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie C.Y., Palmer, Nicholette D., Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E., Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D., Neale, Benjamin M., Purcell, Shaun, Butterworth, Adam S., Howson, Joanna M.M., Lee, Heung Man, Lu, Yingchang, Kwak, Soo Heon, Zhao, Wei, Danesh, John, Lam, Vincent K.L., Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia H.T., Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E., Rybin, Dennis, Farook, Vidya S., Fowler, Sharon P., Freedman, Barry I., Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J., Khor, Chiea Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, Loh, Marie, Musani, Solomon K., Puppala, Sobha, Scott, William R., Yengo, Loïc, Tan, Sian Tsung, Taylor, Herman A., Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C., Mangino, Massimo, Bonnycastle, Lori L., Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L., Herder, Christian, Groves, Christopher J., Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A., Doney, Alex S.F., Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J., Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeriya, Hollensted, Mette, Jørgensen, Marit E., Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Swift, Amy, Rosengren, Anders H., Stirrups, Kathleen, Wood, Andrew R., Mihailov, Evelin, Blancher, Christine, Carneiro, Mauricio O., Maguire, Jared, Poplin, Ryan, Shakir, Khalid, Fennell, Timothy, DePristo, Mark, De Angelis, Martin Hrabé, Deloukas, Panos, Gjesing, Anette P., Jun, Goo, Nilsson, Peter M., Murphy, Jacquelyn, Onofrio, Robert, Thorand, Barbara, Hansen, Torben, Meisinger, Christa, Hu, Frank B., Isomaa, Bo, Karpe, Fredrik, Liang, Liming, Peters, Annette, Huth, Cornelia, O'Rahilly, Stephen P., Palmer, Colin N.A., Pedersen, Oluf, Rauramaa, Rainer, Tuomilehto, Jaakko, Salomaa, Veikko, Watanabe, Richard M., Syvänen, Ann Christine, Bergman, Richard N., Bharadwaj, Dwaipayan, Bottinger, Erwin P., Cho, Yoon Shin, Chandak, Giriraj R., Chan, Juliana C.N., Chia, Kee Seng, Daly, Mark J., Ebrahim, Shah B., Langenberg, Claudia, Elliott, Paul, Jablonski, Kathleen A., Lehman, Donna M., Jia, Weiping, Ma, Ronald C.W., Pollin, Toni I., Sandhu, Manjinder, Tandon, Nikhil, Froguel, Philippe, Barroso, Inês, Teo, Yik Ying, Zeggini, Eleftheria, Loos, Ruth J.F., Small, Kerrin S., Ried, Janina S., DeFronzo, Ralph A., Grallert, Harald, Glaser, Benjamin, Metspalu, Andres, Wareham, Nicholas J., Walker, Mark, Banks, Eric, Gieger, Christian, Ingelsson, Erik, Im, Hae Kyung, Illig, Thomas, Franks, Paul W., Buck, Gemma, Trakalo, Joseph, Buck, David, Prokopenko, Inga, Mägi, Reedik, Lind, Lars, Farjoun, Yossi, Owen, Katharine R., Gloyn, Anna L., Strauch, Konstantin, Tuomi, Tiinamaija, Kooner, Jaspal Singh, Lee, Jong Young, Park, Taesung, Donnelly, Peter, Morris, Andrew D., Hattersley, Andrew T., Bowden, Donald W., Collins, Francis S., Atzmon, Gil, Chambers, John C., Spector, Timothy D., Laakso, Markku, Strom, Tim M., Bell, Graeme I., Blangero, John, Duggirala, Ravindranath, Tai, Eshyong, McVean, Gilean, Hanis, Craig L., Wilson, James G., Seielstad, Mark, Frayling, Timothy M., Meigs, James B., Cox, Nancy J., Sladek, Rob, Lander, Eric S., Gabriel, Stacey, Mohlke, Karen L., Meitinger, Thomas, Groop, Leif, Abecasis, Goncalo, Scott, Laura J., Morris, Andrew P., Kang, Hyun Min, Altshuler, David, Burtt, Noël P., Florez, Jose C., Boehnke, Michael, and McCarthy, Mark I.

Abstract

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ∼82 K Europeans via the exome chip, and ∼90% of low-frequency non-coding variants in ∼44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.

Published
2017

18. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

Author

Mahajan, Anubha, Sim, Xueling, Ng, Hui Jin, Manning, Alisa, Rivas, Manuel A., Highland, Heather M., Locke, Adam E., Grarup, Niels, Im, Hae Kyung, Cingolani, Pablo, Flannick, Jason, Fontanillas, Pierre, Fuchsberger, Christian, Gaulton, Kyle J., Teslovich, Tanya M., Rayner, N. William, Robertson, Neil R., Beer, Nicola L., Rundle, Jana K., Bork-Jensen, Jette, Ladenvall, Claes, Blancher, Christine, Buck, David, Buck, Gemma, Burtt, Noël P., Gabriel, Stacey, Gjesing, Anette P., Groves, Christopher J., Hollensted, Mette, Huyghe, Jeroen R., Jackson, Anne U., Jun, Goo, Justesen, Johanne Marie, Mangino, Massimo, Murphy, Jacquelyn, Neville, Matt, Onofrio, Robert, Small, Kerrin S., Stringham, Heather M., Syvänen, Ann Christine, Trakalo, Joseph, Abecasis, Goncalo, Bell, Graeme I., Blangero, John, Cox, Nancy J., Duggirala, Ravindranath, Hanis, Craig L., Seielstad, Mark, Wilson, James G., Christensen, Cramer, Brandslund, Ivan, Rauramaa, Rainer, Surdulescu, Gabriela L., Doney, Alex S F, Lannfelt, Lars, Linneberg, Allan, Isomaa, Bo, Tuomi, Tiinamaija, Jørgensen, Marit E., Jørgensen, Torben, Kuusisto, Johanna, Uusitupa, Matti, Salomaa, Veikko, Spector, Timothy D., Morris, Andrew D., Palmer, Colin N A, Collins, Francis S., Mohlke, Karen L., Bergman, Richard N., Ingelsson, Erik, Lind, Lars, Tuomilehto, Jaakko, Hansen, Torben, Watanabe, Richard M., Prokopenko, Inga, Dupuis, Josee, Karpe, Fredrik, Groop, Leif, Laakso, Markku, Pedersen, Oluf, Florez, Jose C., Morris, Andrew P., Altshuler, David, Meigs, James B., Boehnke, Michael, McCarthy, Mark I., Lindgren, Cecilia M., Gloyn, Anna L., Abboud, Hanna E., Afzal, Uzma, Aguilar, David, Arya, Rector, Atzmon, Gil, Aung, Tin, Banks, Eric, Barroso, Inês, Barzilai, Nir, Below, Jennifer E., Bharadwaj, Dwaipayan, Blackwell, Thomas W., Bonnycastle, Lori L., Bowden, Don, Carey, Jason, Carneiro, Mauricio O., Chambers, John C., Chan, Edmund, Chan, Juliana, Chandak, Giriraj R., Chen, Peng, Chen, Yuhui, Chen, Han, Cheng, Ching Yu, Chia, Kee Seng, Cho, Yoon Shin, Correa, Adolfo, Curran, Joanne E., Daly, Mark J., Day-Williams, Aaron G., DeFronzo, Ralph A., DePristo, Mark, Donnelly, Peter J., Ebrahim, Shah B., Elliott, Paul, Esko, Tõnu, Fadista, João, Farjoun, Yossi, Farmer, Andrew J., Farook, Vidya S., Fennell, Timothy, Ferreira, Teresa, Fingerlin, Tasha, Forsén, Tom, Fowler, Sharon P., Franks, Paul W., Frayling, Timothy M., Freedman, Barry I., Froguel, Philippe, Gamazon, Eric R., Gieger, Christian, Glaser, Benjamin, Go, Min Jin, Goldstein, Jacqueline I., Grallert, Harald, Grant, George, Green, Todd, Griswold, Michael, Hale, Daniel Esten, Han, Bok Ghee, Hartl, Christopher, Hattersley, Andrew T., Hicks, Pamela J., Hodgkiss, Dylan, Horikoshi, Momoko, Hrabé de Angelis, Martin, Hu, Cheng, Hu, Frank B., Huh, Iksoo, Kamran Ikram, Mohammad, Illig, Thomas, Jablonski, Kathleen A., Jenkinson, Christopher P., Jia, Weiping, Kang, Hyun Min, Khor, Chiea Chuen, Kim, Yongkang, Kim, Young Jin, Kim, Bong Jo, Kinnunen, Leena, Kooner, Jaspal Singh, Kravic, Jasmina, Kriebel, Jennifer, Kumar, Ashish, Kumar, Satish, Kuulasmaa, Teemu, Kwon, Min Seok, Langenberg, Claudia, Lauritzen, Torsten, Lee, Selyeong, Lee, Jaehoon, Lee, Juyoung, Lee, Jong Young, Lehman, Donna M., Lehne, Benjamin, Levy, Jonathan C., Li, Jiang, Liang, Liming, Lim, Wei Yen, Lin, Keng Han, Liu, Jianjun, Loh, Marie, Ma, Ronald C W, Ma, Clement, Mägi, Reedik, Maguire, Jared, Maxwell, Taylor J., McVean, Gilean, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mihailov, Evelin, Milani, Lili, Moutsianas, Loukas, Müller-Nurasyid, Martina, K. Musani, Solomon, Nagai, Yoshihiko, Narisu, Narisu, Neale, Benjamin M., Ng, Maggie C Y, Nilsson, Peter, O'Rahilly, Stephen P., Orho-Melander, Marju, Owen, Katharine R., Palmer, Nicholette D., Park, Taesung, Pasko, Dorota, Pearson, Richard D., Perry, John R B, Peters, Annette, Pollin, Toni I., Poplin, Ryan, Prabhakaran, Dorairaj, Puppala, Sobha, Purcell, Shaun, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Rosengren, Anders H., Sandhu, Manjinder, Schwarzmayr, Thomas, Scott, Laura J., Scott, Robert A., Scott, James, Scott, William R., Sehmi, Jobanpreet, Shakir, Khalid, Sladek, Rob, Smith, Joshua D., Stancáková, Alena, Strauch, Konstantin, Strom, Tim M., Swift, Amy, Tai, E. Shyong, Tajes, Juan Fernandez, Tan, Sian Tsung, Tandon, Nikhil, Taylor, Herman A., Teo, Yik Ying, Thameem, Farook, Thorand, Barbara, van de Bunt, Martijn, Varga, Tibor V., Walker, Mark, Wareham, Nicholas J., Welch, Ryan P., Wieland, Thomas, Wilson, Gregory, Wong, Tien Yin, Wood, Andrew R., Yoon, Joon, Zeggini, Eleftheria, and Zhang, Weihua

Abstract

Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P

Published
2015
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19. Metabolites as Novel Biomarkers for Childhood Obesity-Related Traits in Mexican American Children

Author

Farook, Vidya S., Reddivari, Lavanya, Chittoor, Geetha, Puppala, Sobha, Arya, Rector, Fowler, Sharon P., Hunt, Kelly J., Curran, Joanne E., Comuzzie, Anthony G., Lehman, Donna M., Jenkinson, Christopher P., Lynch, Jane L., DeFronzo, Ralph A., Blangero, John, Hale, Daniel E., Duggirala, Ravindranath, and Vanamala, Jairam

Subjects
Leptin, Male, Pediatric Obesity, Adolescent, Interleukin-6, Tumor Necrosis Factor-alpha, Cholesterol, HDL, Blood Pressure, Lipids, Article, United States, Body Mass Index, C-Reactive Protein, Reference Values, Risk Factors, Mexican Americans, Cytokines, Humans, Insulin, Female, Insulin Resistance, Waist Circumference, Child, Biomarkers, Chemokine CCL2
Abstract

Although newer approaches have identified several metabolites associated with obesity, there is paucity of such information in paediatric populations, especially among Mexican-Americans (MAs) who are at high risk of obesity. Therefore, we performed a global serum metabolite screening in MA children to identify biomarkers of childhood obesity.We selected 15 normal-weight, 13 overweight and 14 obese MA children (6-17 years) and performed global serum metabolite screening using ultra-performance liquid chromatography/quadruple orthogonal acceleration time of flight tandem micro mass spectrometer. Metabolite values were analysed to assess mean differences among groups using one-way analysis of variance, to test for linear trend across groups and to examine Pearson's correlations between them and seven cardiometabolic traits (CMTs): body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, homeostasis model of assessment-insulin resistance, triglycerides and high-density lipoprotein cholesterol.We identified 14 metabolites exhibiting differences between groups as well as linear trend across groups with nominal statistical significance. After adjustment for multiple testing, mean differences and linear trends across groups remained significant (P 5.9 × 10(-5) ) for L-thyronine, bradykinin and naringenin. Of the examined metabolite-CMT trait pairs, all metabolites except for 2-methylbutyroylcarnitine were nominally associated with two or more CMTs, some exhibiting significance even after accounting for multiple testing (P 3.6 × 10(-3) ).To our knowledge, this study - albeit pilot in nature - is the first study to identify these metabolites as novel biomarkers of childhood obesity and its correlates. These findings signify the need for future systematic investigations of metabolic pathways underlying childhood obesity.

Published
2014

20. The genetic architecture of type 2 diabetes

Author

JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epidemiologie, Fuchsberger, Christian, Flannick, Jason, Teslovich, Tanya M, Mahajan, Anubha, Agarwala, Vineeta, Gaulton, Kyle J, Ma, Clement, Fontanillas, Pierre, Moutsianas, Loukas, McCarthy, Davis J, Rivas, Manuel A, Perry, John R B, Sim, Xueling, Blackwell, Thomas W, Robertson, Neil R, Rayner, N William, Cingolani, Pablo, Locke, Adam E, Tajes, Juan Fernandez, Highland, Heather M, Dupuis, Josee, Chines, Peter S, Lindgren, Cecilia M, Hartl, Christopher, Jackson, Anne U, Chen, Han, Huyghe, Jeroen R, van de Bunt, Martijn, Pearson, Richard D, Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M, Gamazon, Eric R, Lee, Jaehoon, Chen, Yuhui, Scott, Robert A, Below, Jennifer E, Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L, Pasko, Dorota, Parker, Stephen C J, Varga, Tibor V, Green, Todd, Beer, Nicola L, Day-Williams, Aaron G, Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong-Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min-Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng-Han, Maxwell, Taylor J, Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P, Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F, Han, Bok-Ghee, Jenkinson, Christopher P, Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie C Y, Palmer, Nicholette D, Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E, Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D, Neale, Benjamin M, Purcell, Shaun, Butterworth, Adam S, Howson, Joanna M M, Lee, Heung Man, Lu, Yingchang, Kwak, Soo-Heon, Zhao, Wei, Danesh, John, Lam, Vincent K L, Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia H T, Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching-Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E, Rybin, Denis, Farook, Vidya S, Fowler, Sharon P, Freedman, Barry I, Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J, Khor, Chiea-Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, van der Schouw, Yvonne T, Loh, Marie, Musani, Solomon K, Puppala, Sobha, Scott, William R, Yengo, Loïc, Tan, Sian-Tsung, Taylor, Herman A, Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C, Mangino, Massimo, Bonnycastle, Lori L, Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L, Herder, Christian, Groves, Christopher J, Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A, Doney, Alex S F, Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J, Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeriya, Hollensted, Mette, Jørgensen, Marit E, Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Swift, Amy, Rosengren, Anders H, Stirrups, Kathleen, Wood, Andrew R, Mihailov, Evelin, Blancher, Christine, Carneiro, Mauricio O, Maguire, Jared, Poplin, Ryan, Shakir, Khalid, Fennell, Timothy, DePristo, Mark, Hrabé de Angelis, Martin, Deloukas, Panos, Gjesing, Anette P, Jun, Goo, Nilsson, Peter, Murphy, Jacquelyn, Onofrio, Robert, Thorand, Barbara, Hansen, Torben, Meisinger, Christa, Hu, Frank B, Isomaa, Bo, Karpe, Fredrik, Liang, Liming, Peters, Annette, Huth, Cornelia, O'Rahilly, Stephen P, Palmer, Colin N A, Pedersen, Oluf, Rauramaa, Rainer, Tuomilehto, Jaakko, Salomaa, Veikko, Watanabe, Richard M, Syvänen, Ann-Christine, Bergman, Richard N, Bharadwaj, Dwaipayan, Bottinger, Erwin P, Cho, Yoon Shin, Chandak, Giriraj R, Chan, Juliana C N, Chia, Kee Seng, Daly, Mark J, Ebrahim, Shah B, Langenberg, Claudia, Elliott, Paul, Jablonski, Kathleen A, Lehman, Donna M, Jia, Weiping, Ma, Ronald C W, Pollin, Toni I, Sandhu, Manjinder, Tandon, Nikhil, Froguel, Philippe, Barroso, Inês, Teo, Yik Ying, Zeggini, Eleftheria, Loos, Ruth J F, Small, Kerrin S, Ried, Janina S, DeFronzo, Ralph A, Grallert, Harald, Glaser, Benjamin, Metspalu, Andres, Wareham, Nicholas J, Walker, Mark, Banks, Eric, Gieger, Christian, Ingelsson, Erik, Im, Hae Kyung, Illig, Thomas, Franks, Paul W, Buck, Gemma, Trakalo, Joseph, Buck, David, Prokopenko, Inga, Mägi, Reedik, Lind, Lars, Farjoun, Yossi, Owen, Katharine R, Gloyn, Anna L, Strauch, Konstantin, Tuomi, Tiinamaija, Kooner, Jaspal Singh, Lee, Jong-Young, Park, Taesung, Donnelly, Peter, Morris, Andrew D, Hattersley, Andrew T, Bowden, Donald W, Collins, Francis S, Atzmon, Gil, Chambers, John C, Spector, Timothy D, Laakso, Markku, Strom, Tim M, Bell, Graeme I, Blangero, John, Duggirala, Ravindranath, Tai, E Shyong, McVean, Gilean, Hanis, Craig L, Wilson, James G, Seielstad, Mark, Frayling, Timothy M, Meigs, James B, Cox, Nancy J, Sladek, Rob, Lander, Eric S, Gabriel, Stacey, Burtt, Noël P, Mohlke, Karen L, Meitinger, Thomas, Groop, Leif, Abecasis, Goncalo, Florez, Jose C, Scott, Laura J, Morris, Andrew P, Kang, Hyun Min, Boehnke, Michael, Altshuler, David, McCarthy, Mark I, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epidemiologie, Fuchsberger, Christian, Flannick, Jason, Teslovich, Tanya M, Mahajan, Anubha, Agarwala, Vineeta, Gaulton, Kyle J, Ma, Clement, Fontanillas, Pierre, Moutsianas, Loukas, McCarthy, Davis J, Rivas, Manuel A, Perry, John R B, Sim, Xueling, Blackwell, Thomas W, Robertson, Neil R, Rayner, N William, Cingolani, Pablo, Locke, Adam E, Tajes, Juan Fernandez, Highland, Heather M, Dupuis, Josee, Chines, Peter S, Lindgren, Cecilia M, Hartl, Christopher, Jackson, Anne U, Chen, Han, Huyghe, Jeroen R, van de Bunt, Martijn, Pearson, Richard D, Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M, Gamazon, Eric R, Lee, Jaehoon, Chen, Yuhui, Scott, Robert A, Below, Jennifer E, Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L, Pasko, Dorota, Parker, Stephen C J, Varga, Tibor V, Green, Todd, Beer, Nicola L, Day-Williams, Aaron G, Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong-Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min-Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng-Han, Maxwell, Taylor J, Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P, Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F, Han, Bok-Ghee, Jenkinson, Christopher P, Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie C Y, Palmer, Nicholette D, Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E, Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D, Neale, Benjamin M, Purcell, Shaun, Butterworth, Adam S, Howson, Joanna M M, Lee, Heung Man, Lu, Yingchang, Kwak, Soo-Heon, Zhao, Wei, Danesh, John, Lam, Vincent K L, Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia H T, Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching-Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E, Rybin, Denis, Farook, Vidya S, Fowler, Sharon P, Freedman, Barry I, Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J, Khor, Chiea-Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, van der Schouw, Yvonne T, Loh, Marie, Musani, Solomon K, Puppala, Sobha, Scott, William R, Yengo, Loïc, Tan, Sian-Tsung, Taylor, Herman A, Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C, Mangino, Massimo, Bonnycastle, Lori L, Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L, Herder, Christian, Groves, Christopher J, Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A, Doney, Alex S F, Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J, Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeriya, Hollensted, Mette, Jørgensen, Marit E, Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Swift, Amy, Rosengren, Anders H, Stirrups, Kathleen, Wood, Andrew R, Mihailov, Evelin, Blancher, Christine, Carneiro, Mauricio O, Maguire, Jared, Poplin, Ryan, Shakir, Khalid, Fennell, Timothy, DePristo, Mark, Hrabé de Angelis, Martin, Deloukas, Panos, Gjesing, Anette P, Jun, Goo, Nilsson, Peter, Murphy, Jacquelyn, Onofrio, Robert, Thorand, Barbara, Hansen, Torben, Meisinger, Christa, Hu, Frank B, Isomaa, Bo, Karpe, Fredrik, Liang, Liming, Peters, Annette, Huth, Cornelia, O'Rahilly, Stephen P, Palmer, Colin N A, Pedersen, Oluf, Rauramaa, Rainer, Tuomilehto, Jaakko, Salomaa, Veikko, Watanabe, Richard M, Syvänen, Ann-Christine, Bergman, Richard N, Bharadwaj, Dwaipayan, Bottinger, Erwin P, Cho, Yoon Shin, Chandak, Giriraj R, Chan, Juliana C N, Chia, Kee Seng, Daly, Mark J, Ebrahim, Shah B, Langenberg, Claudia, Elliott, Paul, Jablonski, Kathleen A, Lehman, Donna M, Jia, Weiping, Ma, Ronald C W, Pollin, Toni I, Sandhu, Manjinder, Tandon, Nikhil, Froguel, Philippe, Barroso, Inês, Teo, Yik Ying, Zeggini, Eleftheria, Loos, Ruth J F, Small, Kerrin S, Ried, Janina S, DeFronzo, Ralph A, Grallert, Harald, Glaser, Benjamin, Metspalu, Andres, Wareham, Nicholas J, Walker, Mark, Banks, Eric, Gieger, Christian, Ingelsson, Erik, Im, Hae Kyung, Illig, Thomas, Franks, Paul W, Buck, Gemma, Trakalo, Joseph, Buck, David, Prokopenko, Inga, Mägi, Reedik, Lind, Lars, Farjoun, Yossi, Owen, Katharine R, Gloyn, Anna L, Strauch, Konstantin, Tuomi, Tiinamaija, Kooner, Jaspal Singh, Lee, Jong-Young, Park, Taesung, Donnelly, Peter, Morris, Andrew D, Hattersley, Andrew T, Bowden, Donald W, Collins, Francis S, Atzmon, Gil, Chambers, John C, Spector, Timothy D, Laakso, Markku, Strom, Tim M, Bell, Graeme I, Blangero, John, Duggirala, Ravindranath, Tai, E Shyong, McVean, Gilean, Hanis, Craig L, Wilson, James G, Seielstad, Mark, Frayling, Timothy M, Meigs, James B, Cox, Nancy J, Sladek, Rob, Lander, Eric S, Gabriel, Stacey, Burtt, Noël P, Mohlke, Karen L, Meitinger, Thomas, Groop, Leif, Abecasis, Goncalo, Florez, Jose C, Scott, Laura J, Morris, Andrew P, Kang, Hyun Min, Boehnke, Michael, Altshuler, David, and McCarthy, Mark I

Published
2016

21. Genome-wide genetic investigation of serological measures of common infections

Author

Rubicz, Rohina, primary, Yolken, Robert, additional, Drigalenko, Eugene, additional, Carless, Melanie A, additional, Dyer, Thomas D, additional, Kent Jr, Jack, additional, Curran, Joanne E, additional, Johnson, Matthew P, additional, Cole, Shelley A, additional, Fowler, Sharon P, additional, Arya, Rector, additional, Puppala, Sobha, additional, Almasy, Laura, additional, Moses, Eric K, additional, Kraig, Ellen, additional, Duggirala, Ravindranath, additional, Blangero, John, additional, Leach, Charles T, additional, and Göring, Harald HH, additional

Published
2015
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22. Genetics of Serum Carotenoid Levels and Obesity Related Traits in Mexican American Children

Author

Farook, Vidya S., primary, Reddivari, Lavanya, additional, Puppala, Sobha, additional, Arya, Rector, additional, Fowler, Sharon P., additional, Chittoor, Geetha, additional, Mohan, Birunda, additional, Jenkinson, Christopher P., additional, Lynch, Jane L., additional, DeFronzo, Ralph A., additional, Blangero, John, additional, Hale, Daniel E., additional, Duggirala, Ravindranath, additional, and Vanamala, Jairam, additional

Published
2013
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23. Metabolic Syndrome Is Linked to Chromosome 7q21 and Associated With Genetic Variants in CD36 and GNAT3 in Mexican Americans

Author

Farook, Vidya S., primary, Puppala, Sobha, additional, Schneider, Jennifer, additional, Fowler, Sharon P., additional, Chittoor, Geetha, additional, Dyer, Thomas D., additional, Allayee, Hooman, additional, Cole, Shelley A., additional, Arya, Rector, additional, Black, Mary H., additional, Curran, Joanne E., additional, Almasy, Laura, additional, Buchanan, Thomas A., additional, Jenkinson, Christopher P., additional, Lehman, Donna M., additional, Watanabe, Richard M., additional, Blangero, John, additional, and Duggirala, Ravindranath, additional

Published
2012
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26. Impact of Diabetes and Comorbidities on Split-Thickness Skin Grafts for Foot Wounds

Author

Ramanujam, Crystal L., Han, David, Fowler, Sharon, Kilpadi, Krista, and Zgonis, Thomas

Abstract

Background:Split-thickness skin grafts can be used for foot wound closure in diabetic and nondiabetic patients. It is unknown whether this procedure is reliable for all diabetic patients, with or without comorbidities of diabetes, including cardiovascular disease, neuropathy, retinopathy, and nephropathy.Methods:We retrospectively reviewed 203 patients who underwent this procedure to determine significant differences in healing time, postoperative infection, and need for revisional surgery and to create a predictive model to identify diabetic patients who are likely to have a successful outcome.Results:Overall, compared with nondiabetic patients, diabetic patients experienced a significantly higher risk of delayed healing time and postoperative complication/infection and, hence, are more likely to require revisional surgery after undergoing the initial split-thickness skin graft procedure. These differences seemed to be related more to the presence of comorbidities than to diabetic status itself. Diabetic patients with preexisting comorbidities experienced a significantly increased risk of delayed healing time and postoperative infection and a higher need for revisional surgery compared with nondiabetic patients or diabetic patients without comorbidities. However, there were no significant differences in outcome between diabetic patients without comorbidities and nondiabetic patients.Conclusions:For individuals with diabetes but without exclusionary comorbidities, split-thickness skin grafting may be considered an effective surgical alternative to other prolonged treatment options currently used in this patient population. (J Am Podiatr Med Assoc 103(3): 223–232, 2013)

Published
2013
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27. 1337-P: Prediction of Insulin Sensitivity Using Serum Carotenoid Concentrations and Pediatric Metabolic Index in Mexican-American Children.

Author

MUMMIDI, SRINIVAS, HERNANDEZ-RUIZ, JOSELIN, FAROOK, VIDYA S., REDDIVARI, LAVANYA, DIAZ-BADILLO, ALVARO, FOWLER, SHARON P., RESENDEZ, ROY G., AKHTAR, FEROZ, LEHMAN, DONNA, JENKINSON, CHRIS, ARYA, RECTOR, LYNCH, JANE L., DEFRONZO, RALPH A., HALE, DANIEL E., BLANGERO, JOHN, LOPEZ-ALVARENGA, JUAN C., DUGGIRALA, RAVINDRANATH, and VANAMALA, JAIRAM K.

Abstract

We have recently reported that serum concentrations of α-carotene (AC) and β-carotene (BC) are under strong genetic influences and were correlated with obesity and other cardio-metabolic traits in Mexican American (MA) children. Our previously developed Pediatric Metabolic Index (PMI) correlates with insulin resistance (IR) after adjusting for age and sex using lipid and adiposity data from Mexican children. A PMI score > 2.0 predicts metabolic abnormalities including IR (i.e., HOMA-IR). Yet data on other MA children with PMI > 2 with normal IR and PMI < 2 with high IR, suggest a role for additional factors in determining insulin sensitivity (IS). In this study, we aimed to assess interactions between carotenoids and the PMI in predicting IS as measured by Matsuda index using the surface-response analysis (SRA). Four different carotenoids, namely, AC, BC, lycopene (Lyc), and β-cryptoxanthin (CX) from ∼590 children enrolled in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth (SAFARI) study were measured by mass spectrometry. Glucose and insulin levels were measured after oral glucose tolerance test and IS index (ISI) was calculated using Matsuda method. SRA was used to determine two-way interactions of serum carotenoids and PMI on ISI. The computer programs SOLAR and STATISTICA 7.0 were used for statistical analysis. The SRA showed an increase in ISI in children with PMI scores between 2 to 4. This effect was modified in the presence of lower serum AC and BC levels; and, interactions between these two carotenoids and PMI had maximal effect on ISI. Conversely, MA children with moderate PMI scores can have substantial improvement in their IS with higher serum AC and BC levels. In contrast, there was a minimal surface response to Lyc and CX serum levels. Notably, despite an optimal PMI, children with lower concentrations of AC and BC showed less IS. In summary, we found that interactions between carotenoids with PMI may predict IS in MA children. Disclosure: S. Mummidi: None. J. Hernandez-Ruiz: None. V.S. Farook: None. L. Reddivari: None. A. Diaz-Badillo: None. S.P. Fowler: None. R.G. Resendez: None. F. Akhtar: None. D. Lehman: None. C. Jenkinson: None. R. Arya: None. J.L. Lynch: Board Member; Self; American Academy of Pediatrics. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Daiichi Sankyo Company, Limited, National Institutes of Health, Novo Nordisk Inc., Pediatric Diabetes Consortium. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. D.E. Hale: None. J. Blangero: None. J.C. Lopez-Alvarenga: None. R. Duggirala: None. J.K. Vanamala: None. Funding: National Institutes of Health (R01HD049051, R01AI119131, HD049051-5S1, HD041111, DK053889, DK042273, DK047482, P01HL45522, MH59490, M01-RR-01346), U.S. Department of Veterans Affairs; Max and Minnie Tomerlin Voelcker Fund; National Institute of Food and Agriculture (2009-55200-05197) [ABSTRACT FROM AUTHOR]

Published
2019
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28. Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

Author

Flannick, Jason, Fuchsberger, Christian, Mahajan, Anubha, Teslovich, Tanya M, Agarwala, Vineeta, Gaulton, Kyle J, Caulkins, Lizz, Koesterer, Ryan, Ma, Clement, Moutsianas, Loukas, McCarthy, Davis J, Rivas, Manuel A, Perry, John RB, Sim, Xueling, Blackwell, Thomas W, Robertson, Neil R, Rayner, N William, Cingolani, Pablo, Locke, Adam E, Tajes, Juan Fernandez, Highland, Heather M, Dupuis, Josee, Chines, Peter S, Lindgren, Cecilia M, Hartl, Christopher, Jackson, Anne U, Chen, Han, Huyghe, Jeroen R, Van De Bunt, Martijn, Pearson, Richard D, Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M, Gamazon, Eric R, Lee, Jaehoon, Chen, Yuhui, Scott, Robert A, Below, Jennifer E, Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L, Pasko, Dorota, Parker, Stephen CJ, Varga, Tibor V, Green, Todd, Beer, Nicola L, Day-Williams, Aaron G, Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong-Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min-Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng-Han, Maxwell, Taylor J, Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P, Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F, Han, Bok-Ghee, Jenkinson, Christopher P, Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie CY, Palmer, Nicholette D, Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E, Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D, Neale, Benjamin M, Purcell, Shaun, Butterworth, Adam S, Howson, Joanna MM, Lee, Heung Man, Lu, Yingchang, Kwak, Soo-Heon, Zhao, Wei, Danesh, John, Lam, Vincent KL, Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia HT, Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching-Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E, Rybin, Dennis, Farook, Vidya S, Fowler, Sharon P, Freedman, Barry I, Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J, Khor, Chiea-Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, Loh, Marie, Musani, Solomon K, Puppala, Sobha, Scott, William R, Yengo, Loïc, Tan, Sian-Tsung, Taylor, Herman A, Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C, Mangino, Massimo, Bonnycastle, Lori L, Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L, Herder, Christian, Groves, Christopher J, Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A, Doney, Alex SF, Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J, Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeri, Hollensted, Mette, Jørgensen, Marit E, Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Swift, Amy, Rosengren, Anders H, Stirrups, Kathleen, Wood, Andrew R, Mihailov, Evelin, Blancher, Christine, Carneiro, Mauricio O, Maguire, Jared, Poplin, Ryan, Shakir, Khalid, Fennell, Timothy, DePristo, Mark, De Angelis, Martin Hrabé, Deloukas, Panos, Gjesing, Anette P, Jun, Goo, Nilsson, Peter, Murphy, Jacquelyn, Onofrio, Robert, Thorand, Barbara, Hansen, Torben, Meisinger, Christa, Hu, Frank B, Isomaa, Bo, Karpe, Fredrik, Liang, Liming, Peters, Annette, Huth, Cornelia, O'Rahilly, Stephen P, Palmer, Colin NA, Pedersen, Oluf, Rauramaa, Rainer, Tuomilehto, Jaakko, Salomaa, Veikko, Watanabe, Richard M, Syvänen, Ann-Christine, Bergman, Richard N, Bharadwaj, Dwaipayan, Bottinger, Erwin P, Cho, Yoon Shin, Chandak, Giriraj R, Chan, Juliana Cn, Chia, Kee Seng, Daly, Mark J, Ebrahim, Shah B, Langenberg, Claudia, Elliott, Paul, Jablonski, Kathleen A, Lehman, Donna M, Jia, Weiping, Ma, Ronald CW, Pollin, Toni I, Sandhu, Manjinder, Tandon, Nikhil, Froguel, Philippe, Barroso, Inês, Teo, Yik Ying, Zeggini, Eleftheria, Loos, Ruth JF, Small, Kerrin S, Ried, Janina S, DeFronzo, Ralph A, Grallert, Harald, Glaser, Benjamin, Metspalu, Andres, Wareham, Nicholas J, Walker, Mark, Banks, Eric, Gieger, Christian, Ingelsson, Erik, Im, Hae Kyung, Illig, Thomas, Franks, Paul W, Buck, Gemma, Trakalo, Joseph, Buck, David, Prokopenko, Inga, Mägi, Reedik, Lind, Lars, Farjoun, Yossi, Owen, Katharine R, Gloyn, Anna L, Strauch, Konstantin, Tuomi, Tiinamaija, Kooner, Jaspal Singh, Lee, Jong-Young, Park, Taesung, Donnelly, Peter, Morris, Andrew D, Hattersley, Andrew T, Bowden, Donald W, Collins, Francis S, Atzmon, Gil, Chambers, John C, Spector, Timothy D, Laakso, Markku, Strom, Tim M, Bell, Graeme I, Blangero, John, Duggirala, Ravindranath, Tai, E Shyong, McVean, Gilean, Hanis, Craig L, Wilson, James G, Seielstad, Mark, Frayling, Timothy M, Meigs, James B, Cox, Nancy J, Sladek, Rob, Lander, Eric S, Gabriel, Stacey, Mohlke, Karen L, Meitinger, Thomas, Groop, Leif, Abecasis, Goncalo, Scott, Laura J, Morris, Andrew P, Kang, Hyun Min, Altshuler, David, Burtt, Noël P, Florez, Jose C, Boehnke, Michael, and McCarthy, Mark I

Subjects
Diabetes Mellitus, Type 2, Genetic Variation, Humans, White People, 3. Good health
Abstract

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.

30. The Metabolic Syndrome in Mexican American Children: Preliminary Findings from the San Antonio Family Assessment of Metabolic Risk Indicators in Youth (SAFARI) Study.

Author

Duggirala, Ravindranath, Fowler, Sharon P., Schneider, Jennifer, Puppala, Sobha, Farook, Vidya S., Hunt, Kelly J., Arya, Rector, Bradshaw, Benjamin, Almasy, Laura, Comuzzie, Anthony G., Lynch, Jane L., Jenkinson, Christopher P., MacCluer, Jean W., Defronzo, Ralph A., Blangero, John, and Hale, Daniel E.

Subjects
*METABOLIC syndrome, *HEALTH risk assessment, *CHILDHOOD obesity, *TYPE 2 diabetes, *MEXICAN American children, *GLUCOSE, *BODY mass index, *PREDIABETIC state, *DISEASES
Abstract

The prevalence rates of obesity, type 2 diabetes (T2DM), and the Metabolic Syndrome (MS) have been increasing at alarming rates in children. We are conducting a community-based study, called SAFARI, to determine the precursors of MS in Mexican American children; compare MS profiles between these children and adult members of their families; and verify whether variants in candidate genes found to be associated with MS traits in adults have any relevance to similar traits in children. Our study participants are the children (aged 6-17 years) of adult members of three well-established San Antonio-based Mexican American family studies. As of 12-12-2006, 219 children had participated (111 girls and 108 boys, mean age = 12 years) in our study. A variety of data - metabolic, anthropometric, behavioral, and dietary - have been collected from each child; comparable metabolic and anthropometric data were collected for their parents and other adults in their extended families. The prevalence rates of T2DM, impaired fasting glucose, and impaired glucose tolerance are ∼0.5%, ∼9% and ∼ 18%, respectively. The mean body mass index [BMI: kg/m²] is ∼23. About 48% of the children are at risk of being overweight and ∼32% are overweight. Several of the phenotypes have shown significant heritabilities [p-value] (e.g., fasting glucose = 28% [0.04], BMI = 72% [0.00003], total cholesterol = 54% [0.003], triglycerides = 79% [0.0006], systolic blood pressure = 62% [0.0003], and urine albumin/creatinine ratio = 58% [0.003]). In conclusion, these preliminary data reveal a high risk of overweight in almost half the Mexican American children studied, an alarming occurrence of pre-diabetes in these children, and strong genetic influences over key MS-related traits. [ABSTRACT FROM AUTHOR]

Published
2007

31. Search for Genetic Variants in Positional Candidate Genes on Chromosome 7q21 Region Linked to Metabolic Syndrome in Mexican Americans.

Author

Farook, Vidya S., Puppala, Sobha, Arya, Rector, Schneider, Jennifer, Fowler, Sharon P., Dyer, Thomas D., Cole, Shelly A., Almasy, Laura, Blangero, John, and Duggirala, Ravindranath

Subjects
CHROMOSOMES, TYPE 2 diabetes, METABOLIC syndrome, GENES, FATTY acids, NUCLEOTIDE sequence, MEXICAN Americans
Abstract

Metabolic syndrome (MS) is a constellation of abnormalities such as obesity, insulin resistance, impaired glucose tolerance, and dyslipidemia. Previously, we found linkage between MS (NCEP/ATPIII) and a region on chromosome 7q near markers D7S2212/D7S821, using data from the San Antonio Family Diabetes/Gallbladder Study (SAFDGS). Multiple studies have implicated this 7q chromosomal region to influence type 2 diabetes related traits. We have started screening some of the positional candidate genes for genetic variants that could explain our initial MS linkage signal. This study reports the association between MS and genetic variants in two positional candidate genes: fatty acid translocase (FAT or CD36) and its neighboring gene guanine nucleotide binding protein, alpha transducing 3 (GNAT3). In regard to CD36, we sequenced DNA from 30 SAFDGS participants for all the exons and its flanking regions, 5'-UTRs, 3'-UTRs, and 2 kb of the promoter regions of the previously reported alternative transcripts of CD36 and identified 22 SNPs. Of these SNPs, 7 were unique and 15 were already reported in the dbSNP database. We only genotyped 19 CD36 SNPs which were polymorphic, and probes were either available or designed by Applied Biosystems in ∼720 SAFDGS subjects. Also, we genotyped 11 GNAT3 SNPs selected from the dbSNP. We performed association analysis between these SNPs and MS using the measured genotype approach as implemented in SOLAR. All SNPs were in HWE except one CD36 SNP, and the minor allele frequencies ranged from 0.5% - 46%. Of the 18 SNPs in CD36, 4 showed association with MS (p < 0.05), but one (rs1194197) with relatively high significance (p = 0.003). Of the 11 SNPs in GNAT3, 5 showed some evidence for association (p < 0.06), while one of them (rs11760281) showed the strongest evidence for association (p = 0.0006) with MS. In conclusion, our study suggests that genetic variation in the CD36 region significantly influences MS in Mexican Americans. [ABSTRACT FROM AUTHOR]

Published
2007

33. Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans.

Author

Fowler SPG

Subjects
Animals, Diet adverse effects, Humans, Non-Nutritive Sweeteners administration & dosage, Non-Nutritive Sweeteners chemistry, Weight Gain physiology, Homeostasis physiology, Non-Nutritive Sweeteners adverse effects
Abstract

For more than a decade, pioneering animal studies conducted by investigators at Purdue University have provided evidence to support a central thesis: that the uncoupling of sweet taste and caloric intake by low-calorie sweeteners (LCS) can disrupt an animal's ability to predict the metabolic consequences of sweet taste, and thereby impair the animal's ability to respond appropriately to sweet-tasting foods. These investigators' work has been replicated and extended internationally. There now exists a body of evidence, from a number of investigators, that animals chronically exposed to any of a range of LCSs - including saccharin, sucralose, acesulfame potassium, aspartame, or the combination of erythritol+aspartame - have exhibited one or more of the following conditions: increased food consumption, lower post-prandial thermogenesis, increased weight gain, greater percent body fat, decreased GLP-1 release during glucose tolerance testing, and significantly greater fasting glucose, glucose area under the curve during glucose tolerance testing, and hyperinsulinemia, compared with animals exposed to plain water or - in many cases - even to calorically-sweetened foods or liquids. Adverse impacts of LCS have appeared diminished in animals on dietary restriction, but were pronounced among males, animals genetically predisposed to obesity, and animals with diet-induced obesity. Impacts have been especially striking in animals on high-energy diets: diets high in fats and sugars, and diets which resemble a highly-processed 'Western' diet, including trans-fatty acids and monosodium glutamate. These studies have offered both support for, and biologically plausible mechanisms to explain, the results from a series of large-scale, long-term prospective observational studies conducted in humans, in which longitudinal increases in weight, abdominal adiposity, and incidence of overweight and obesity have been observed among study participants who reported using diet sodas and other LCS-sweetened beverages daily or more often at baseline. Furthermore, frequent use of diet beverages has been associated prospectively with increased long-term risk and/or hazard of a number of cardiometabolic conditions usually considered to be among the sequelae of obesity: hypertension, metabolic syndrome, diabetes, depression, kidney dysfunction, heart attack, stroke, and even cardiovascular and total mortality. Reverse causality does not appear to explain fully the increased risk observed across all of these studies, the majority of which have included key potential confounders as covariates. These have included body mass index or waist circumference at baseline; total caloric intake and specific macronutrient intake; physical activity; smoking; demographic and other relevant risk factors; and/or family history of disease. Whether non-LCS ingredients in diet beverages might have independently increased the weight gain and/or cardiometabolic risk observed among frequent consumers of LCS-sweetened beverages deserves further exploration. In the meantime, however, there is a striking congruence between results from animal research and a number of large-scale, long-term observational studies in humans, in finding significantly increased weight gain, adiposity, incidence of obesity, cardiometabolic risk, and even total mortality among individuals with chronic, daily exposure to low-calorie sweeteners - and these results are troubling., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Published
2016
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34. Diet soda intake is associated with long-term increases in waist circumference in a biethnic cohort of older adults: the San Antonio Longitudinal Study of Aging.

Author

Fowler SP, Williams K, and Hazuda HP

Subjects
Aged, Body Height, Body Mass Index, Body Weight, Cohort Studies, Ethnicity, Female, Humans, Longitudinal Studies, Male, Mexican Americans, Obesity, Abdominal etiology, Prospective Studies, Texas, Carbonated Beverages, Waist Circumference
Abstract

Objectives: To examine the relationship between diet soda (DS) intake (DSI) and long-term waist circumference (WC) change (ΔWC) in the biethnic San Antonio Longitudinal Study of Aging (SALSA)., Design: Prospective cohort study., Setting: San Antonio, Texas, neighborhoods., Participants: SALSA examined 749 Mexican-American and European-American individuals aged 65 and older at baseline (baseline, 1992-96); 474 (79.1%) survivors completed follow-up 1 (FU1, 2000-01), 413 (73.4%) completed FU2 (2001-03), and 375 (71.0%) completed FU3 (2003-04). Participants completed a mean of 2.64 follow-up intervals, for 9.4 total follow-up years., Measurements: DSI, WC, height, and weight were measured at outset and at the conclusion of each interval: baseline, FU1, FU2, and FU3., Results: Adjusted for initial WC, demographic characteristics, physical activity, diabetes mellitus, and smoking, mean interval ΔWC of DS users (2.11 cm, 95% confidence interval (CI) = 1.45-2.76 cm) was almost triple that of nonusers (0.77 cm, 95% CI = 0.29-1.23 cm) (P < .001). Adjusted interval ΔWCs were 0.77 cm (95% CI = 0.29-1.23 cm) for nonusers, 1.76 cm (95% CI = 0.96-2.57 cm) for occasional users, and 3.04 cm (95% CI = 1.82-4.26 cm) for daily users (P = .002 for trend). This translates to ΔWCs of 0.80 inches for nonusers, 1.83 inches for occasional users, and 3.16 for daily users over the total SALSA follow-up. In subanalyses stratified for selected covariates, ΔWC point estimates were consistently higher in DS users., Conclusion: In a striking dose-response relationship, increasing DSI was associated with escalating abdominal obesity, a potential pathway for cardiometabolic risk in this aging population., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Published
2015
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