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306 results on '"Viñuela, Ana"'

1. Role of human plasma metabolites in prediabetes and type 2 diabetes from the IMI-DIRECT study

Author

Sharma, Sapna, Dong, Qiuling, Haid, Mark, Adam, Jonathan, Bizzotto, Roberto, Fernandez-Tajes, Juan J., Jones, Angus G., Tura, Andrea, Artati, Anna, Prehn, Cornelia, Kastenmüller, Gabi, Koivula, Robert W., Franks, Paul W., Walker, Mark, Forgie, Ian M., Giordano, Giuseppe, Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Manolis, McCarthy, Mark I., Pedersen, Oluf, Schwenk, Jochen M., Tsirigos, Konstantinos D., De Masi, Federico, Brunak, Soren, Viñuela, Ana, Mari, Andrea, McDonald, Timothy J., Kokkola, Tarja, Adamski, Jerzy, Pearson, Ewan R., and Grallert, Harald

Published
2024
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3. Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

Author

Brown, Andrew A., Fernandez-Tajes, Juan J., Hong, Mun-gwan, Brorsson, Caroline A., Koivula, Robert W., Davtian, David, Dupuis, Théo, Sartori, Ambra, Michalettou, Theodora-Dafni, Forgie, Ian M., Adam, Jonathan, Allin, Kristine H., Caiazzo, Robert, Cederberg, Henna, De Masi, Federico, Elders, Petra J. M., Giordano, Giuseppe N., Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison J., Howald, Cédric, Jones, Angus G., Kokkola, Tarja, Laakso, Markku, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Mourby, Miranda, Musholt, Petra B., Nilsson, Birgitte, Pattou, Francois, Penet, Deborah, Raverdy, Violeta, Ridderstråle, Martin, Romano, Luciana, Rutters, Femke, Sharma, Sapna, Teare, Harriet, ‘t Hart, Leen, Tsirigos, Konstantinos D., Vangipurapu, Jagadish, Vestergaard, Henrik, Brunak, Søren, Franks, Paul W., Frost, Gary, Grallert, Harald, Jablonka, Bernd, McCarthy, Mark I., Pavo, Imre, Pedersen, Oluf, Ruetten, Hartmut, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., Pearson, Ewan R., Dermitzakis, Emmanouil T., and Viñuela, Ana

Published
2023
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4. Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases

Author

Carland, Corinne, Png, Grace, Malarstig, Anders, Kho, Pik Fang, Gustafsson, Stefan, Michaelsson, Karl, Lind, Lars, Tsafantakis, Emmanouil, Karaleftheri, Maria, Dedoussis, George, Ramisch, Anna, Macdonald-Dunlop, Erin, Klaric, Lucija, Joshi, Peter K., Chen, Yan, Björck, Hanna M., Eriksson, Per, Carrasco-Zanini, Julia, Wheeler, Eleanor, Suhre, Karsten, Gilly, Arthur, Zeggini, Eleftheria, Viñuela, Ana, Dermitzakis, Emmanouil T., Wilson, James F., Langenberg, Claudia, Thareja, Gaurav, Halama, Anna, Schmidt, Frank, Zanetti, Daniela, and Assimes, Themistocles

Published
2023
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5. Deletion of ABCB10 in beta-cells protects from high-fat diet induced insulin resistance

Author

Shum, Michael, Segawa, Mayuko, Gharakhanian, Raffi, Viñuela, Ana, Wortham, Matthew, Baghdasarian, Siyouneh, Wolf, Dane M, Sereda, Samuel B, Nocito, Laura, Stiles, Linsey, Zhou, Zhiqiang, Gutierrez, Vincent, Sander, Maike, Shirihai, Orian S, and Liesa, Marc

Subjects
Biochemistry and Cell Biology, Biological Sciences, Obesity, Diabetes, Nutrition, Genetics, 2.1 Biological and endogenous factors, Metabolic and endocrine, ATP-Binding Cassette Transporters, Animals, Blood Glucose, Diabetes Mellitus, Type 2, Diet, High-Fat, Female, Glucose, Glucose Tolerance Test, Insulin, Insulin Resistance, Insulin Secretion, Insulin-Secreting Cells, Islets of Langerhans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Insulin resistance, Beta-cell, ABCB10, Physiology, Biochemistry and cell biology
Abstract

ObjectiveThe contribution of beta-cell dysfunction to type 2 diabetes (T2D) is not restricted to insulinopenia in the late stages of the disease. Elevated fasting insulinemia in normoglycemic humans is a major factor predicting the onset of insulin resistance and T2D, demonstrating an early alteration of beta-cell function in T2D. Moreover, an early and chronic increase in fasting insulinemia contributes to insulin resistance in high-fat diet (HFD)-fed mice. However, whether there are genetic factors that promote beta-cell-initiated insulin resistance remains undefined. Human variants of the mitochondrial transporter ABCB10, which regulates redox by increasing bilirubin synthesis, have been associated with an elevated risk of T2D. The effects of T2D ABCB10 variants on ABCB10 expression and the actions of ABCB10 in beta-cells are unknown.MethodsThe expression of beta-cell ABCB10 was analyzed in published transcriptome datasets from human beta-cells carrying the T2D-risk ABCB10 variant. Insulin sensitivity, beta-cell proliferation, and secretory function were measured in beta-cell-specific ABCB10 KO mice (Ins1Cre-Abcb10flox/flox). The short-term role of beta-cell ABCB10 activity on glucose-stimulated insulin secretion (GSIS) was determined in isolated islets.ResultsCarrying the T2Drisk allele G of ABCB10 rs348330 variant was associated with increased ABCB10 expression in human beta-cells. Constitutive deletion of Abcb10 in beta-cells protected mice from hyperinsulinemia and insulin resistance by limiting HFD-induced beta-cell expansion. An early limitation in GSIS and H2O2-mediated signaling caused by elevated ABCB10 activity can initiate an over-compensatory expansion of beta-cell mass in response to HFD. Accordingly, increasing ABCB10 expression was sufficient to limit GSIS capacity. In health, ABCB10 protein was decreased during islet maturation, with maturation restricting beta-cell proliferation and elevating GSIS. Finally, ex-vivo and short-term deletion of ABCB10 in islets isolated from HFD-fed mice increased H2O2 and GSIS, which was reversed by bilirubin treatments.ConclusionsBeta-cell ABCB10 is required for HFD to induce insulin resistance in mice by amplifying beta-cell mass expansion to maladaptive levels that cause fasting hyperinsulinemia.

Published
2022

7. The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study.

Author

Eriksen, Rebeca, White, Margaret C, Dawed, Adem Y, Perez, Isabel Garcia, Posma, Joram M, Haid, Mark, Sharma, Sapna, Prehn, Cornelia, Thomas, E Louise, Koivula, Robert W, Bizzotto, Roberto, Mari, Andrea, Giordano, Giuseppe N, Pavo, Imre, Schwenk, Jochen M, Masi, Federico De, Tsirigos, Konstantinos D, Brunak, Søren, Viñuela, Ana, and Mahajan, Anubha

Subjects
TYPE 2 diabetes, PEOPLE with diabetes, MULTIPLE regression analysis, INSULIN resistance, FOOD consumption
Abstract

Context The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood. Objective We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D. Methods We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D. Results Our multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin-resistant phenotype and observe a strong independent relationship with male sex, increased adiposity, and liver fat, particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycemia, higher adiposity, liver fat, male sex, and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit, and vegetables in people with prediabetes, and with a high intake of red meat and alcohol in people with diabetes. Conclusion These studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake, and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

Author

Wesolowska-Andersen, Agata, Brorsson, Caroline A., Bizzotto, Roberto, Mari, Andrea, Tura, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Prehn, Cornelia, Artati, Anna, Hong, Mun-Gwan, Musholt, Petra B., Kurbasic, Azra, De Masi, Federico, Tsirigos, Kostas, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Thomas, Cecilia Engel, Banasik, Karina, Jennison, Chrisopher, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, Louise, Frost, Gary, Thomsen, Henrik, Allin, Kristine, Hansen, Tue Haldor, Vestergaard, Henrik, Hansen, Torben, Rutters, Femke, Elders, Petra, t’Hart, Leen, Bonnefond, Amelie, Canouil, Mickaël, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Hattersley, Andrew, McDonald, Timothy, Teare, Harriet, Ridderstrale, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Froguel, Philippe, Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, Pearson, Ewan, McCarthy, Mark I., and Brunak, Søren

Published
2022
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9. Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition.

Author

Small, Kerrin, Todorčević, Marijana, Civelek, Mete, El-Sayed Moustafa, Julia, Wang, Xiao, Simon, Michelle, Fernandez-Tajes, Juan, Mahajan, Anubha, Horikoshi, Momoko, Hugill, Alison, Glastonbury, Craig, Quaye, Lydia, Neville, Matt, Sethi, Siddharth, Yon, Marianne, Pan, Calvin, Che, Nam, Viñuela, Ana, Tsai, Pei-Chien, Nag, Abhishek, Buil, Alfonso, Thorleifsson, Gudmar, Raghavan, Avanthi, Ding, Qiurong, Morris, Andrew, Bell, Jordana, Thorsteinsdottir, Unnur, Stefansson, Kari, Laakso, Markku, Dahlman, Ingrid, Arner, Peter, Gloyn, Anna, Musunuru, Kiran, Lusis, Aldons, Cox, Roger, Karpe, Fredrik, and McCarthy, Mark

Subjects
Adipocytes, Alleles, Animals, Body Composition, Body Fat Distribution, Cell Size, Diabetes Mellitus, Type 2, Enhancer Elements, Genetic, Female, Gene Expression, Genome-Wide Association Study, Genomic Imprinting, Humans, Kruppel-Like Transcription Factors, Lipogenesis, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Risk Factors, Sex Characteristics, Sp Transcription Factors
Abstract

Individual risk of type 2 diabetes (T2D) is modified by perturbations to the mass, distribution and function of adipose tissue. To investigate the mechanisms underlying these associations, we explored the molecular, cellular and whole-body effects of T2D-associated alleles near KLF14. We show that KLF14 diabetes-risk alleles act in adipose tissue to reduce KLF14 expression and modulate, in trans, the expression of 385 genes. We demonstrate, in human cellular studies, that reduced KLF14 expression increases pre-adipocyte proliferation but disrupts lipogenesis, and in mice, that adipose tissue-specific deletion of Klf14 partially recapitulates the human phenotype of insulin resistance, dyslipidemia and T2D. We show that carriers of the KLF14 T2D risk allele shift body fat from gynoid stores to abdominal stores and display a marked increase in adipocyte cell size, and that these effects on fat distribution, and the T2D association, are female specific. The metabolic risk associated with variation at this imprinted locus depends on the sex both of the subject and of the parent from whom the risk allele derives.

Published
2018

12. 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, Viñuela, 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, Noël P, Chen, Yuhui, Green, Todd, Hartl, Christopher, Kang, Hyun Min, Kumar, Ashish, Ladenvall, Claes, Ma, Clement, Moutsianas, Loukas, Pearson, Richard D, Perry, John RB, Rayner, N William, Robertson, Neil R, Scott, Laura J, van de Bunt, Martijn, Eriksson, Johan G, Jula, Antti, Koskinen, Seppo, Lehtimäki, Terho, Palotie, Aarno, Raitakari, Olli T, Jacobs, Suzanne BR, 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, Hrabé de Angelis, Martin, 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 SF, Nilsson, Peter, Wareham, Nicholas J, Langenberg, Claudia, Varga, Tibor V, Franks, Paul W, Rolandsson, Olov, Rosengren, Anders H, and Farook, Vidya S

Subjects
Genetics, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Black or African American, Alleles, Asian People, Case-Control Studies, Diabetes Mellitus, Type 2, Fasting, Finland, Gene Frequency, Genetic Predisposition to Disease, Genotype, Hispanic or Latino, Humans, Insulin, Insulin Resistance, Odds Ratio, Proto-Oncogene Proteins c-akt, White People, Medical and Health Sciences, Endocrinology & Metabolism
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

13. Differential expression analyses on aortic tissue reveal novel genes and pathways associated with abdominal aortic aneurysm onset and progression

Author

Temprano-Sagrera, Gerard, primary, Soto, Begoña, additional, Dilmé, Jaume, additional, Peypoch, Olga, additional, Calsina-Juscafresa, Laura, additional, Davtian, David, additional, Nieto, Lluis, additional, Brown, Andrew, additional, Escudero, José-Román, additional, Viñuela, Ana, additional, Camacho, Mercedes, additional, and Sabater-Lleal, Maria, additional

Published
2024
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16. Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration

Author

Jennison, Christopher, Ehrhardt, Beate, Baum, Patrick, Schoelsch, Corinna, Freijer, Jan, Grempler, Rolf, Graefe-Mody, Ulrike, Hennige, Anita, Dings, Christiane, Lehr, Thorsten, Scherer, Nina, Sihinecich, Iryna, Pattou, Francois, Raverdi, Violeta, Caiazzo, Robert, Torres, Fanelly, Verkindt, Helene, Mari, Andrea, Tura, Andrea, Giorgino, Toni, Bizzotto, Roberto, Froguel, Philippe, Bonneford, Amelie, Canouil, Mickael, Dhennin, Veronique, Brorsson, Caroline, Brunak, Soren, De Masi, Federico, Gudmundsdóttir, Valborg, Pedersen, Helle, Banasik, Karina, Thomas, Cecilia, Sackett, Peter, Staerfeldt, Hans-Henrik, Lundgaard, Agnete, Nilsson, Birgitte, Nielsen, Agnes, Mazzoni, Gianluca, Karaderi, Tugce, Rasmussen, Simon, Johansen, Joachim, Allesøe, Rosa, Fritsche, Andreas, Thorand, Barbara, Adamski, Jurek, Grallert, Harald, Haid, Mark, Sharma, Sapna, Troll, Martina, Adam, Jonathan, Ferrer, Jorge, Eriksen, Heather, Frost, Gary, Haussler, Ragna, Hong, Mun-gwan, Schwenk, Jochen, Uhlen, Mathias, Nicolay, Claudia, Pavo, Imre, Steckel-Hamann, Birgit, Thomas, Melissa, Adragni, Kofi, Wu, Han, Hart, Leen't, Roderick, Slieker, van Leeuwen, Nienke, Dekkers, Koen, Frau, Francesca, Gassenhuber, Johann, Jablonka, Bernd, Musholt, Petra, Ruetten, Hartmut, Tillner, Joachim, Baltauss, Tania, Bernard Poenaru, Oana, de Preville, Nathalie, Rodriquez, Marianne, Arumugam, Manimozhiyan, Allin, Kristine, Engelbrechtsen, Line, Hansen, Torben, Hansen, Tue, Forman, Annemette, Jonsson, Anna, Pedersen, Oluf, Dutta, Avirup, Vogt, Josef, Vestergaard, Henrik, Laakso, Markku, Kokkola, Tarja, Kuulasmaa, Teemu, Franks, Paul, Giordano, Nick, Pomares-Millan, Hugo, Fitipaldi, Hugo, Mutie, Pascal, Klintenberg, Maria, Bergstrom, Margit, Groop, Leif, Ridderstrale, Martin, Atabaki Pasdar, Naeimeh, Deshmukh, Harshal, Heggie, Alison, Wake, Dianne, McEvoy, Donna, McVittie, Ian, Walker, Mark, Hattersley, Andrew, Hill, Anita, Jones, Angus, McDonald, Timothy, Perry, Mandy, Nice, Rachel, Hudson, Michelle, Thorne, Claire, Dermitzakis, Emmanouil, Viñuela, Ana, Cabrelli, Louise, Loftus, Heather, Dawed, Adem, Donnelly, Louise, Forgie, Ian, Pearson, Ewan, Palmer, Colin, Brown, Andrew, Koivula, Robert, Wesolowska-Andersen, Agata, Abdalla, Moustafa, McRobert, Nicky, Fernandez, Juan, Jiao, Yunlong, Robertson, Neil, Gough, Stephen, Kaye, Jane, Mourby, Miranda, Mahajan, Anubha, McCarthy, Mark, Shah, Nisha, Teare, Harriet, Holl, Reinhard, Koopman, Anitra, Rutters, Femke, Beulens, Joline, Groeneveld, Lenka, Bell, Jimmy, Thomas, Louise, Whitcher, Brandon, Wilman, Henry R., Parisinos, Constantinos A., Atabaki-Pasdar, Naeimeh, Kelly, Matt, Thomas, E. Louise, Neubauer, Stefan, Hingorani, Aroon D., Patel, Riyaz S., Hemingway, Harry, Franks, Paul W., Bell, Jimmy D., Banerjee, Rajarshi, and Yaghootkar, Hanieh

Published
2019
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17. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author

Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M, de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce BJ, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, and Ripatti, Samuli

Subjects
Biological Sciences, Genetics, Human Genome, Rare Diseases, Lung, Cancer, Lung Cancer, Respiratory, Cohort Studies, Databases, Genetic, Follow-Up Studies, Forced Expiratory Volume, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Lung Diseases, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Prognosis, Quantitative Trait Loci, Respiratory Function Tests, Spirometry, Vital Capacity, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

Published
2014

18. Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium

Author

Koivula, Robert W., Forgie, Ian M., Kurbasic, Azra, Viñuela, Ana, Heggie, Alison, Giordano, Giuseppe N., Hansen, Tue H., Hudson, Michelle, Koopman, Anitra D. M., Rutters, Femke, Siloaho, Maritta, Allin, Kristine H., Brage, Søren, Brorsson, Caroline A., Dawed, Adem Y., De Masi, Federico, Groves, Christopher J., Kokkola, Tarja, Mahajan, Anubha, Perry, Mandy H., Rauh, Simone P., Ridderstråle, Martin, Teare, Harriet J. A., Thomas, E. Louise, Tura, Andrea, Vestergaard, Henrik, White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline W., Brunak, Søren, Dermitzakis, Emmanouil T., Froguel, Philippe, Frost, Gary, Gupta, Ramneek, Hansen, Torben, Hattersley, Andrew, Jablonka, Bernd, Kaye, Jane, Laakso, Markku, McDonald, Timothy J., Pedersen, Oluf, Schwenk, Jochen M., Pavo, Imre, Mari, Andrea, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Franks, Paul W., and for the IMI DIRECT Consortium

Published
2019
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19. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans.

Author

Mangino, Massimo, Hwang, Shih-Jen, Spector, Timothy, Hunt, Steven, Kimura, Masayuki, Fitzpatrick, Annette, Christiansen, Lene, Petersen, Inge, Elbers, Clara, Harris, Tamara, Chen, Wei, Srinivasan, Sathanur, Kark, Jeremy, Benetos, Athanase, El Shamieh, Said, Visvikis-Siest, Sophie, Christensen, Kaare, Berenson, Gerald, Valdes, Ana, Viñuela, Ana, Garcia, Melissa, Arnett, Donna, Broeckel, Ulrich, Province, Michael, Pankow, James, Kammerer, Candace, Liu, Yongmei, Nalls, Michael, Tishkoff, Sarah, Thomas, Fridtjof, Psaty, Bruce, Bis, Joshua, Taylor, Kent, Smith, Erin, Schork, Nicholas, Levy, Daniel, Aviv, Abraham, Ziv, Elad, and Rotter, Jerome

Subjects
Genome-Wide Association Study, Humans, Kruppel-Like Transcription Factors, Telomere, Telomere Homeostasis, Telomere-Binding Proteins
Abstract

Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10(-11)) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10(-8)). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10(-8)) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10(-8)) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.

Published
2012

20. Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

Author

Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, De Masi, Federico, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Gupta, Ramneek, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Hong, Mun-Gwan, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstråle, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Vangipurapu, Jagadish, Vestergaard, Henrik, Viñuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark I., Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Søren

Published
2020
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21. Genome-Wide Association Shows that Pigmentation Genes Play a Role in Skin Aging

Author

Law, Matthew H., Medland, Sarah E., Zhu, Gu, Yazar, Seyhan, Viñuela, Ana, Wallace, Leanne, Shekar, Sri Niranjan, Duffy, David L., Bataille, Veronique, Glass, Dan, Spector, Tim D., Wood, Diane, Gordon, Scott D., Barbour, Julie M., Henders, Anjali K., Hewitt, Alex W., Montgomery, Grant W., Sturm, Richard A., Mackey, David A., Green, Adèle C., Martin, Nicholas G., and MacGregor, Stuart

Published
2017
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22. Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D

Author

Viñuela, Ana, Varshney, Arushi, van de Bunt, Martijn, Prasad, Rashmi B., Asplund, Olof, Bennett, Amanda, Boehnke, Michael, Brown, Andrew A., Erdos, Michael R., Fadista, João, Hansson, Ola, Hatem, Gad, Howald, Cédric, Iyengar, Apoorva K., Johnson, Paul, Krus, Ulrika, MacDonald, Patrick E., Mahajan, Anubha, Manning Fox, Jocelyn E., Narisu, Narisu, Nylander, Vibe, Orchard, Peter, Oskolkov, Nikolay, Panousis, Nikolaos I., Payne, Anthony, Stitzel, Michael L., Vadlamudi, Swarooparani, Welch, Ryan, Collins, Francis S., Mohlke, Karen L., Gloyn, Anna L., Scott, Laura J., Dermitzakis, Emmanouil T., Groop, Leif, Parker, Stephen C. J., and McCarthy, Mark I.

Published
2020
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23. La distribución de cine de autor español en Francia: En busca de los públicos de Blancanieves y Las brujas de Zugarramurdi

Author

Viñuela, Ana

Subjects
Marketing de films, Independent Distribution, Cine español, Marketing de películas, Film Marketing, Global Art Cinema, Cinéma d’auteur global, Marché cinématographique français, Mercado francés del cine, Distribution indépendante, Spanish Cinema, French Film Market, Cinéma espagnol, Distribución independiente, Cine de autor global
Abstract

Este artículo propone un acercamiento a los públicos del cine de autor español en las salas francesas mediante el examen de la estrategia de promoción de una película, cuyo punto de partida es la prefiguración de la audiencia por parte del distribuidor. El sector de la distribución independiente en Francia desempeña un papel determinante en la existencia y la visibilidad del cine de autor y en la transformación de la autoría en marca utilizable en la promoción de las obras, especialmente cuando no se pueden comercializar bajo una marca nacional reconocible. En la actualidad, este sector debe enfrentarse a cambios en las formas de consumo y en los procesos de recomendación de películas. Para ilustrar estas cuestiones, recurrimos al análisis de la distribución y la recepción en Francia de Blancanieves (Pablo Berger, 2012) y Las Brujas de Zugarramurdi (Álex de la Iglesia, 2013). This article explores the film audiences of Spanish art-house cinema in France by examining the strategy implemented in promoting a film, for which the starting point is the prefiguration of the audience by the distributor. Independent distributors in France play a fundamental role in the existence and visibility of auteur cinema, as well as for the transformation of authorship into a brand for film promotion, especially when these films cannot be marketed under a recognizable national brand. Indeed, today this sector is challenged by changes in the forms of consumption, as well as in how films are recommended. To illustrate these questions, we discuss the distribution and reception of two Spanish films in France, Blancanieves (Pablo Berger, 2012) and Las Brujas de Zugarramurdi / Witching & Bitching (Álex de la Iglesia, 2013). Cet article propose une approche des publics du cinéma d’auteur espagnol dans les salles françaises à travers l’examen de la stratégie de promotion d’un film, dont le point de départ est la préfiguration du public par le distributeur. Le secteur de la distribution indépendante en France joue un rôle de premier plan dans l’existence et la visibilité du cinéma d’auteur et dans la transformation de l’auctorialité en marque susceptible d’être utilisée dans la promotion des œuvres, en particulier quand celles-ci ne peuvent être commercialisées sous une marque nationale identifiable. À l’heure actuelle, ce secteur doit faire face aux changements des modes de consommation et des processus de recommandation des films. Pour illustrer ces questions, nous analysons la distribution et la réception en France de Blancanieves (Pablo Berger, 2012) et de Las brujas de Zugarramurdi / Les Sorcières de Zugarramurdi (Álex de la Iglesia, 2013).

Published
2023

25. Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases

Author

Carland, Corinne, primary, Png, Grace, additional, Malarstig, Anders, additional, Kho, Pik Fang, additional, Gustafsson, Stefan, additional, Michaelsson, Karl, additional, Lind, Lars, additional, Tsafantakis, Emmanouil, additional, Karaleftheri, Maria, additional, Dedoussis, George, additional, Ramisch, Anna, additional, Macdonald-Dunlop, Erin, additional, Klaric, Lucija, additional, Joshi, Peter K., additional, Chen, Yan, additional, Björck, Hanna M., additional, Eriksson, Per, additional, Carrasco-Zanini, Julia, additional, Wheeler, Eleanor, additional, Suhre, Karsten, additional, Gilly, Arthur, additional, Zeggini, Eleftheria, additional, Viñuela, Ana, additional, Dermitzakis, Emmanouil T., additional, Wilson, James F., additional, Langenberg, Claudia, additional, Thareja, Gaurav, additional, Halama, Anna, additional, Schmidt, Frank, additional, Consortium, SCALLOP, additional, Zanetti, Daniela, additional, and Assimes, Themistocles, additional

Published
2023
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26. Mapping poverty at the local level in Europe: A consistent spatial disaggregation of the AROPE indicator for France, Spain, Portugal and the United Kingdom

Author

Díaz Dapena, Alberto, Fernández Vázquez, Esteban, Rubiera Morollón, Fernando, Viñuela, Ana, Díaz Dapena, Alberto, Fernández Vázquez, Esteban, Rubiera Morollón, Fernando, and Viñuela, Ana

Abstract

In the EU, territorial inequalities in terms of income and poverty have been broadly analysed at the national and regional levels. However, mainly due to the lack of reliable data, very little attention has been paid to territorial inequalities within European regions, namely, at a more local level, such as in metropolitan areas, cities or neighbourhoods. This paper proposes a methodology to disaggregate official regional poverty figures into poverty indicators for smaller spatial units, mainly local administrative units. For each country, poverty figures at the regional level from household surveys are combined with microcensus data that contain details on the local entities of residence to disaggregate the regional poverty indicator. In contrast to previous methodologies, our proposed technique guarantees consistency between the local poverty estimates and the regional poverty figures through a second step that adjusts the initial estimates based on generalized cross entropy. The procedure is applied for four European countries: France, Spain, the United Kingdom and Portugal. The resulting local estimates provide an intraregional map of poverty and some insights into the particular behaviour of the capital regions and the disparities between city centres and their surrounding areas., En la UE, las desigualdades territoriales en cuanto a ingresos y pobreza se han analizado ampliamente a nivel nacional y regional. Sin embargo, debido principalmente a la falta de datos fiables, se ha prestado muy poca atención a las desigualdades territoriales dentro de las regiones europeas a un nivel más local, como pueden ser las zonas metropolitanas, las ciudades o los barrios. En el presente artículo se propone una metodología para desglosar las cifras regionales oficiales de pobreza en indicadores de pobreza para unidades espaciales más pequeñas, principalmente unidades administrativas locales. Para cada país, se combinan las cifras de pobreza a nivel regional procedentes de las encuestas de hogares con datos de microcensos que contienen detalles sobre las entidades locales de residencia para desglosar el indicador de pobreza regional. A diferencia de las metodologías anteriores, la técnica que se propone aquí garantiza la coherencia entre las estimaciones de pobreza locales y las cifras de pobreza regionales mediante un segundo paso que ajusta las estimaciones iniciales basadas en la entropía cruzada generalizada. El procedimiento se aplica en cuatro países europeos: Francia, España, el Reino Unido y Portugal. Las estimaciones locales resultantes proporcionan un mapa intrarregional de la pobreza y algunas percepciones del comportamiento particular de las regiones que albergan la capital y las disparidades entre los centros de las ciudades y sus zonas circundantes.

Published
2023

27. Multiallelic Copy Number Variation in ORM1 is Associated with Plasma Cell-Free DNA Levels as an Intermediate Phenotype for Venous Thromboembolism

Author

Martin-Fernandez, Laura, additional, Garcia-Martínez, Iris, additional, Lopez, Sonia, additional, Martinez-Perez, Angel, additional, Vilalta, Noelia, additional, Plaza, Melania, additional, Moret, Carla, additional, Viñuela, Ana, additional, Brown, Andrew A., additional, Panousis, Nikolaos I., additional, Buil, Alfonso, additional, Dermitzakis, Emmanouil T., additional, Corrales, Irene, additional, Souto, Juan Carlos, additional, Vidal, Francisco, additional, and Soria, Jose Manuel, additional

Published
2023
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31. Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health

Author

Tsai, Pei-Chien, Glastonbury, Craig A., Eliot, Melissa N., Bollepalli, Sailalitha, Yet, Idil, Castillo-Fernandez, Juan E., Carnero-Montoro, Elena, Hardiman, Thomas, Martin, Tiphaine C., Vickers, Alice, Mangino, Massimo, Ward, Kirsten, Pietiläinen, Kirsi H., Deloukas, Panos, Spector, Tim D., Viñuela, Ana, Loucks, Eric B., Ollikainen, Miina, Kelsey, Karl T., Small, Kerrin S., and Bell, Jordana T.

Published
2018
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33. Integrated GWAS and Gene Expression Suggest ORM1 as a Potential Regulator of Plasma Levels of Cell-Free DNA and Thrombosis Risk

Author

Lopez, Sonia, additional, Martinez-Perez, Angel, additional, Rodriguez-Rius, Alba, additional, Viñuela, Ana, additional, Brown, Andrew A., additional, Martin-Fernandez, Laura, additional, Vilalta, Noelia, additional, Arús, Marc, additional, Panousis, Nikolaos I., additional, Buil, Alfonso, additional, Sabater-Lleal, Maria, additional, Souto, Juan Carlos, additional, Dermitzakis, Emmanouil T., additional, and Soria, Jose Manuel, additional

Published
2022
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35. Immigrants' spatial concentration: Region or locality attractiveness?

Author

Viñuela, Ana

Subjects
Attractiveness, Population ageing, Geography, Spatial justice, media_common.quotation_subject, Geography, Planning and Development, Immigration, Locality, Demographic economics, ComputingMilieux_MISCELLANEOUS, Demography, media_common
Abstract

We thank the European Union's Horizon 2020 research and innovation programme, Grant/Award Number: 726950, for funding this study.

Published
2021

37. Deletion of ABCB10 in beta-cells protects from high-fat diet induced insulin resistance

Author

Shum, Michael, primary, Segawa, Mayuko, additional, Gharakhanian, Raffi, additional, Viñuela, Ana, additional, Wortham, Matthew, additional, Baghdasarian, Siyouneh, additional, Wolf, Dane M., additional, Sereda, Samuel B., additional, Nocito, Laura, additional, Stiles, Linsey, additional, Zhou, Zhiqiang, additional, Gutierrez, Vincent, additional, Sander, Maike, additional, Shirihai, Orian S., additional, and Liesa, Marc, additional

Published
2021
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38. Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study

Author

Atabaki-Pasdar, Naeimeh, primary, Pomares-Millan, Hugo, additional, Koivula, Robert W, additional, Tura, Andrea, additional, Brown, Andrew, additional, Viñuela, Ana, additional, Agudelo, Leandro, additional, Coral, Daniel, additional, van Oort, Sabine, additional, Allin, Kristine, additional, Chabanova, Elizaveta, additional, Cederberg, Henna, additional, De Masi, Federico, additional, Elders, Petra, additional, Tajes, Juan Fernandez, additional, Forgie, Ian M, additional, Hansen, Tue H, additional, Heggie, Alison, additional, Jones, Angus, additional, Kokkola, Tarja, additional, Mahajan, Anubha, additional, McDonald, Timothy J, additional, McEvoy, Donna, additional, Tsirigos, Konstantinos, additional, Teare, Harriet, additional, Vangipurapu, Jagadish, additional, Vestergaard, Henrik, additional, Adamski, Jerzy, additional, Beulens, Joline WJ, additional, Brunak, Søren, additional, Dermitzakis, Emmanouil, additional, Hansen, Torben, additional, Hattersley, Andrew T, additional, Laakso, Markku, additional, Pedersen, Oluf, additional, Ridderstråle, Martin, additional, Ruetten, Hartmut, additional, Rutters, Femke, additional, Schwenk, Jochen M, additional, Walker, Mark, additional, Giordano, Giuseppe N, additional, Ohlsson, Mattias, additional, Gupta, Ramneek, additional, Mari, Andrea, additional, McCarthy, Mark I, additional, Thomas, E Louise, additional, Bell, Jimmy D, additional, Pavo, Imre, additional, Pearson, Ewan R, additional, and Franks, Paul W, additional

Published
2021
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39. Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Author

Amin Al Olama, Ali, Dadaev, Tokhir, Hazelett, Dennis J., Li, Qiuyan, Leongamornlert, Daniel, Saunders, Edward J., Stephens, Sarah, Cieza-Borrella, Clara, Whitmore, Ian, Benlloch Garcia, Sara, Giles, Graham G., Southey, Melissa C., Fitzgerald, Liesel, Gronberg, Henrik, Wiklund, Fredrik, Aly, Markus, Henderson, Brian E., Schumacher, Fredrick, Haiman, Christopher A., Schleutker, Johanna, Wahlfors, Tiina, Tammela, Teuvo L., Nordestgaard, Børge G., Key, Tim J., Travis, Ruth C., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Pharoah, Paul, Pashayan, Nora, Khaw, Kay-Tee, Stanford, Janet L., Thibodeau, Stephen N., Mcdonnell, Shannon K., Schaid, Daniel J., Maier, Christiane, Vogel, Walther, Luedeke, Manuel, Herkommer, Kathleen, Kibel, Adam S., Cybulski, Cezary, Wokołorczyk, Dominika, Kluzniak, Wojciech, Cannon-Albright, Lisa, Brenner, Hermann, Butterbach, Katja, Arndt, Volker, Park, Jong Y., Sellers, Thomas, Lin, Hui-Yi, Slavov, Chavdar, Kaneva, Radka, Mitev, Vanio, Batra, Jyotsna, Clements, Judith A., Spurdle, Amanda, Teixeira, Manuel R., Paulo, Paula, Maia, Sofia, Pandha, Hardev, Michael, Agnieszka, Kierzek, Andrzej, Govindasami, Koveela, Guy, Michelle, Lophatonanon, Artitaya, Muir, Kenneth, Viñuela, Ana, Brown, Andrew A., Freedman, Mathew, Conti, David V., Easton, Douglas, Coetzee, Gerhard A., Eeles, Rosalind A., Kote-Jarai, Zsofia, Easton, Douglas F., Pharoah, Paul, Michailidou, Kyriaki, Bolla, Manjeet K., Wang, Qin, Berchuck, Andrew, Eeles, Rosalind A., Easton, Douglas F., Kote-Jarai, Zsofia, Al Olama, Ali Amin, Benlloch, Sara, Chenevix-Trench, Georgia, Antoniou, Antonis, McGuffog, Lesley, Couch, Fergus, Offit, Ken, Dennis, Joe, Dunning, Alison M., Lee, Andrew, Dicks, Ed, Luccarini, Craig, Benitez, Javier, Gonzalez-Neira, Anna, Simard, Jacques, Tessier, Daniel C., Bacot, Francois, Vincent, Daniel, LaBoissière, Sylvie, Robidoux, Frederic, Bojesen, Stig E., Nielsen, Sune F., Nordestgaard, Borge G., Cunningham, Julie M., Windebank, Sharon A., Hilker, Christopher A., and Meyer, Jeffrey

Published
2015
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40. Circulating Proteomic Signatures of Chronological Age

Author

Menni, Cristina, Kiddle, Steven J., Mangino, Massimo, Viñuela, Ana, Psatha, Maria, Steves, Claire, Sattlecker, Martina, Buil, Alfonso, Newhouse, Stephen, Nelson, Sally, Williams, Stephen, Voyle, Nicola, Soininen, Hilkka, Kloszewska, Iwona, Mecocci, Patrizia, Tsolaki, Magda, Vellas, Bruno, Lovestone, Simon, Spector, Tim D., Dobson, Richard, and Valdes, Ana M.

Published
2015
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41. Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-hour OGTT: An IMI DIRECT Study

Author

Tura, Andrea, primary, Grespan, Eleonora, primary, Göbl, Christian S., primary, Koivula, Robert W., primary, Franks, Paul W., primary, Pearson, Ewan R., primary, Walker, Mark, primary, Forgie, Ian M., primary, Giordano, Giuseppe N., primary, Pavo, Imre, primary, Ruetten, Hartmut, primary, Dermitzakis, Emmanouil T., primary, McCarthy, Mark I., primary, Pedersen, Oluf, primary, Schwenk, Jochen M., primary, Adamski, Jerzy, primary, Masi, Federico De, primary, Tsirigos, Konstantinos D., primary, Brunak, Søren, primary, Viñuela, Ana, primary, Mahajan, Anubha, primary, McDonald, Timothy J., primary, Kokkola, Tarja, primary, Vangipurapu, Jagadish, primary, Cederberg, Henna, primary, Laakso, Markku, primary, Rutters, Femke, primary, Elders, Petra J.M., primary, Koopman, Anitra D.M., primary, Beulens, Joline W., primary, Ridderstråle, Martin, primary, Hansen, Tue H., primary, Allin, Kristine H., primary, Hansen, Torben, primary, Vestergaard, Henrik, primary, Mari, Andrea, primary, and Consortium, IMI DIRECT, primary

Published
2021
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42. Profiles of glucose metabolism in different prediabetes phenotypes, classified by fasting glycemia, 2-hour OGTT, glycated hemoglobin, and 1-hour OGTT:An IMI DIRECT study

Author

Tura, Andrea, Grespan, Eleonora, Göbl, Christian S, Koivula, Robert W, Franks, Paul W, Pearson, Ewan R, Walker, Mark, Forgie, Ian M, Giordano, Giuseppe N, Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil T, McCarthy, Mark I, Pedersen, Oluf, Schwenk, Jochen M, Adamski, Jerzy, De Masi, Federico, Tsirigos, Konstantinos D, Brunak, Søren, Viñuela, Ana, Mahajan, Anubha, McDonald, Timothy J, Kokkola, Tarja, Vangipurapu, Jagadish, Cederberg, Henna, Laakso, Markku, Rutters, Femke, Elders, Petra J M, Koopman, Anitra D M, Beulens, Joline W, Ridderstråle, Martin, Hansen, Tue H, Allin, Kristine H, Hansen, Torben, Vestergaard, Henrik, Mari, Andrea, Tura, Andrea, Grespan, Eleonora, Göbl, Christian S, Koivula, Robert W, Franks, Paul W, Pearson, Ewan R, Walker, Mark, Forgie, Ian M, Giordano, Giuseppe N, Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil T, McCarthy, Mark I, Pedersen, Oluf, Schwenk, Jochen M, Adamski, Jerzy, De Masi, Federico, Tsirigos, Konstantinos D, Brunak, Søren, Viñuela, Ana, Mahajan, Anubha, McDonald, Timothy J, Kokkola, Tarja, Vangipurapu, Jagadish, Cederberg, Henna, Laakso, Markku, Rutters, Femke, Elders, Petra J M, Koopman, Anitra D M, Beulens, Joline W, Ridderstråle, Martin, Hansen, Tue H, Allin, Kristine H, Hansen, Torben, Vestergaard, Henrik, and Mari, Andrea

Abstract

Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants (N=2111) underwent 2h-75g OGTT at baseline and 48 months. HbA1c was also measured. We classified participants as having isolated prediabetes defect (impaired fasting glucose, IFG; impaired glucose tolerance, IGT; HbA1c-prediabetes, IA1c), two defects (IFG+IGT, IFG+IA1c, IGT+IA1c), or all defects (IFG+IGT+IA1c). Beta-cell function (BCF) and insulin sensitivity (IS) were assessed from OGTT. At baseline, when pooling participants with isolated defects, they showed impairment in both BCF and IS compared to healthy controls. Pooled groups with two or three defects showed progressive further deterioration. Among groups with isolated defect, IGT showed lower IS, insulin secretion at reference glucose (ISRr), and insulin secretion potentiation (p<0.002). Conversely, IA1c showed higher IS and ISRr (p<0.0001). Among groups with two defects, we similarly found differences in both BCF and IS. At 48 months, we found higher type 2 diabetes incidence for progressively increasing number of prediabetes defects (odds ratio >2, p<0.008). In conclusion, the prediabetes groups showed differences in type/degree of glucometabolic impairment. Compared to the pooled group with isolated defects, those with double or triple defect showed progressive differences in diabetes incidence.

Published
2021

43. Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity

Author

Deshmukh, Harshal A, Madsen, Anne Lundager, Viñuela, Ana, Have, Christian Theil, Grarup, Niels, Tura, Andrea, Mahajan, Anubha, Heggie, Alison J, Koivula, Robert W, De Masi, Federico, Tsirigos, Konstantinos K, Linneberg, Allan, Drivsholm, Thomas, Pedersen, Oluf, Sørensen, Thorkild I A, Astrup, Arne, Gjesing, Anette A P, Pavo, Imre, Wood, Andrew R, Ruetten, Hartmut, Jones, Angus G, Koopman, Anitra D M, Cederberg, Henna, Rutters, Femke, Ridderstrale, Martin, Laakso, Markku, McCarthy, Mark I, Frayling, Tim M, Ferrannini, Ele, Franks, Paul W, Pearson, Ewan R, Mari, Andrea, Hansen, Torban, Walker, Mark, Deshmukh, Harshal A, Madsen, Anne Lundager, Viñuela, Ana, Have, Christian Theil, Grarup, Niels, Tura, Andrea, Mahajan, Anubha, Heggie, Alison J, Koivula, Robert W, De Masi, Federico, Tsirigos, Konstantinos K, Linneberg, Allan, Drivsholm, Thomas, Pedersen, Oluf, Sørensen, Thorkild I A, Astrup, Arne, Gjesing, Anette A P, Pavo, Imre, Wood, Andrew R, Ruetten, Hartmut, Jones, Angus G, Koopman, Anitra D M, Cederberg, Henna, Rutters, Femke, Ridderstrale, Martin, Laakso, Markku, McCarthy, Mark I, Frayling, Tim M, Ferrannini, Ele, Franks, Paul W, Pearson, Ewan R, Mari, Andrea, Hansen, Torban, and Walker, Mark

Abstract

Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta cell glucose sensitivity.Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies.Design: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and non-diabetic subjects from 6 independent cohorts (n=5,706). Beta-cell glucose sensitivity was calculated from mixed-meal and oral glucose tolerance tests, and its associations between known glycaemia related SNPS and GWAS SNPs were estimated using linear regression models.Results: Beta-cell glucose sensitivity was moderately heritable (h2 ranged between 34 to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P-value=2.64x10-9) and rs9368219 in the CDKAL1 (P-value=3.15x10-9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity.Conclusion: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta cell glucose sensitivity.

Published
2021

44. Age-dependent changes in mean and variance of gene expression across tissues in a twin cohort

Author

Viñuela, Ana, Brown, Andrew A., Buil, Alfonso, Tsai, Pei-Chien, Davies, Matthew N., Bell, Jordana T., Dermitzakis, Emmanouil T., Spector, Timothy D., Small, Kerrin S., Viñuela, Ana, Brown, Andrew A., Buil, Alfonso, Tsai, Pei-Chien, Davies, Matthew N., Bell, Jordana T., Dermitzakis, Emmanouil T., Spector, Timothy D., and Small, Kerrin S.

Abstract

Changes in the mean and variance of gene expression with age have consequences for healthy aging and disease development. Age-dependent changes in phenotypic variance have been associated with a decline in regulatory functions leading to increase in disease risk. Here, we investigate age-related mean and variance changes in gene expression measured by RNA-seq of fat, skin, whole blood and derived lymphoblastoid cell lines (LCLs) expression from 855 adult female twins. We see evidence of up to 60% of age effects on transcription levels shared across tissues, and 47% of those on splicing. Using gene expression variance and discordance between genetically identical MZ twin pairs, we identify 137 genes with age-related changes in variance and 42 genes with age-related discordance between co-twins; implying the latter are driven by environmental effects. We identify four eQTLs whose effect on expression is age-dependent (FDR 5%). Combined, these results show a complicated mix of environmental and genetically driven changes in expression with age. Using the twin structure in our data, we show that additive genetic effects explain considerably more of the variance in gene expression than aging, but less that other environmental factors, potentially explaining why reliable expression-derived biomarkers for healthy-aging have proved elusive compared with those derived from methylation.

Published
2021

46. Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

Author

de Goede, Olivia M., primary, Nachun, Daniel C., additional, Ferraro, Nicole M., additional, Gloudemans, Michael J., additional, Rao, Abhiram S., additional, Smail, Craig, additional, Eulalio, Tiffany Y., additional, Aguet, François, additional, Ng, Bernard, additional, Xu, Jishu, additional, Barbeira, Alvaro N., additional, Castel, Stephane E., additional, Kim-Hellmuth, Sarah, additional, Park, YoSon, additional, Scott, Alexandra J., additional, Strober, Benjamin J., additional, Brown, Christopher D., additional, Wen, Xiaoquan, additional, Hall, Ira M., additional, Battle, Alexis, additional, Lappalainen, Tuuli, additional, Im, Hae Kyung, additional, Ardlie, Kristin G., additional, Mostafavi, Sara, additional, Quertermous, Thomas, additional, Kirkegaard, Karla, additional, Montgomery, Stephen B., additional, Anand, Shankara, additional, Gabriel, Stacey, additional, Getz, Gad A., additional, Graubert, Aaron, additional, Hadley, Kane, additional, Handsaker, Robert E., additional, Huang, Katherine H., additional, Li, Xiao, additional, MacArthur, Daniel G., additional, Meier, Samuel R., additional, Nedzel, Jared L., additional, Nguyen, Duyen T., additional, Segrè, Ayellet V., additional, Todres, Ellen, additional, Balliu, Brunilda, additional, Bonazzola, Rodrigo, additional, Brown, Andrew, additional, Conrad, Donald F., additional, Cotter, Daniel J., additional, Cox, Nancy, additional, Das, Sayantan, additional, Dermitzakis, Emmanouil T., additional, Einson, Jonah, additional, Engelhardt, Barbara E., additional, Eskin, Eleazar, additional, Flynn, Elise D., additional, Fresard, Laure, additional, Gamazon, Eric R., additional, Garrido-Martín, Diego, additional, Gay, Nicole R., additional, Guigó, Roderic, additional, Hamel, Andrew R., additional, He, Yuan, additional, Hoffman, Paul J., additional, Hormozdiari, Farhad, additional, Hou, Lei, additional, Jo, Brian, additional, Kasela, Silva, additional, Kashin, Seva, additional, Kellis, Manolis, additional, Kwong, Alan, additional, Li, Xin, additional, Liang, Yanyu, additional, Mangul, Serghei, additional, Mohammadi, Pejman, additional, Muñoz-Aguirre, Manuel, additional, Nobel, Andrew B., additional, Oliva, Meritxell, additional, Park, Yongjin, additional, Parsana, Princy, additional, Reverter, Ferran, additional, Rouhana, John M., additional, Sabatti, Chiara, additional, Saha, Ashis, additional, Stephens, Matthew, additional, Stranger, Barbara E., additional, Teran, Nicole A., additional, Viñuela, Ana, additional, Wang, Gao, additional, Wright, Fred, additional, Wucher, Valentin, additional, Zou, Yuxin, additional, Ferreira, Pedro G., additional, Li, Gen, additional, Melé, Marta, additional, Yeger-Lotem, Esti, additional, Bradbury, Debra, additional, Krubit, Tanya, additional, McLean, Jeffrey A., additional, Qi, Liqun, additional, Robinson, Karna, additional, Roche, Nancy V., additional, Smith, Anna M., additional, Tabor, David E., additional, Undale, Anita, additional, Bridge, Jason, additional, Brigham, Lori E., additional, Foster, Barbara A., additional, Gillard, Bryan M., additional, Hasz, Richard, additional, Hunter, Marcus, additional, Johns, Christopher, additional, Johnson, Mark, additional, Karasik, Ellen, additional, Kopen, Gene, additional, Leinweber, William F., additional, McDonald, Alisa, additional, Moser, Michael T., additional, Myer, Kevin, additional, Ramsey, Kimberley D., additional, Roe, Brian, additional, Shad, Saboor, additional, Thomas, Jeffrey A., additional, Walters, Gary, additional, Washington, Michael, additional, Wheeler, Joseph, additional, Jewell, Scott D., additional, Rohrer, Daniel C., additional, Valley, Dana R., additional, Davis, David A., additional, Mash, Deborah C., additional, Barcus, Mary E., additional, Branton, Philip A., additional, Sobin, Leslie, additional, Barker, Laura K., additional, Gardiner, Heather M., additional, Mosavel, Maghboeba, additional, Siminoff, Laura A., additional, Flicek, Paul, additional, Haeussler, Maximilian, additional, Juettemann, Thomas, additional, Kent, W. James, additional, Lee, Christopher M., additional, Powell, Conner C., additional, Rosenbloom, Kate R., additional, Ruffier, Magali, additional, Sheppard, Dan, additional, Taylor, Kieron, additional, Trevanion, Stephen J., additional, Zerbino, Daniel R., additional, Abell, Nathan S., additional, Akey, Joshua, additional, Chen, Lin, additional, Demanelis, Kathryn, additional, Doherty, Jennifer A., additional, Feinberg, Andrew P., additional, Hansen, Kasper D., additional, Hickey, Peter F., additional, Jasmine, Farzana, additional, Jiang, Lihua, additional, Kaul, Rajinder, additional, Kibriya, Muhammad G., additional, Li, Jin Billy, additional, Li, Qin, additional, Lin, Shin, additional, Linder, Sandra E., additional, Pierce, Brandon L., additional, Rizzardi, Lindsay F., additional, Skol, Andrew D., additional, Smith, Kevin S., additional, Snyder, Michael, additional, Stamatoyannopoulos, John, additional, Tang, Hua, additional, Wang, Meng, additional, Carithers, Latarsha J., additional, Guan, Ping, additional, Koester, Susan E., additional, Little, A. Roger, additional, Moore, Helen M., additional, Nierras, Concepcion R., additional, Rao, Abhi K., additional, Vaught, Jimmie B., additional, and Volpi, Simona, additional

Published
2021
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47. Analysis pipeline for 'The impact of sex on gene expression across human tissues'

Author

Oliva, Meritxell, Muñoz-Aguirre, Manuel, Kim-Hellmuth, Sarah, Wucher, Valentin, Gewirtz, Ariel D.H., Cotter, Daniel J., Parsana, Princy, Kasela, Silva, Balliu, Brunilda, Viñuela, Ana, Castel, Stephane E., Mohammadi, Pejman, Aguet, François, Zou, Yuxin, Khramtsova, Ekaterina A., Skol, Andrew D., Garrido-Martín, Diego, Reverter, Ferran, Brown, Andrew, Evans, Patrick, Gamazon, Eric R., Payne, Anthony, Bonazzola, Rodrigo, Barbeira, Alvaro N., Hamel, Andrew R., Martinez-Perez, Angel, Soria, José Manuel, GTEx Consortium, Pierce, Brandon L., Stephens, Matthew, Eskin, Eleazar, Dermitzakis, Emmanouil T., Segrè, Ayellet V., Im, Hae Kyung, Engelhardt, Barbara E., Ardlie, Kristin G., Montgomery, Stephen B., Battle, Alexis J., Lappalainen, Tuuli, Guigó, Roderic, and Stranger, Barbara E.

Subjects
gene expression
Abstract

Sex-biased gene expression analysis pipeline for the research publication "The impact of sex on gene expressionacross human tissues". Details on how to set up and runthe pipeline are available on the README.md file.

Published
2020
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48. Additional file 1 of Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

Author

Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, Masi, Federico De, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Ramneek Gupta, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Mun-Gwan Hong, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Anubha Mahajan, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstråle, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Jagadish Vangipurapu, Vestergaard, Henrik, Viñuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark I., Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Søren

Abstract

Additional file 1. Supplementary Figures. This file contains Fig. S1 – S13.

Published
2020
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49. Predicting and elucidating the etiology of fatty liver disease:A machine learning modeling and validation study in the IMI DIRECT cohorts

Author

Atabaki-Pasdar, Naeimeh, Ohlsson, Mattias, Viñuela, Ana, Frau, Francesca, Pomares-Millan, Hugo, Haid, Mark, Jones, Angus G, Thomas, E Louise, Koivula, Robert W, Kurbasic, Azra, Mutie, Pascal M, Fitipaldi, Hugo, Fernandez, Juan, Dawed, Adem Y, Giordano, Giuseppe N, Forgie, Ian M, McDonald, Timothy J, Rutters, Femke, Cederberg, Henna, Chabanova, Elizaveta, Dale, Matilda, Masi, Federico De, Thomas, Cecilia Engel, Allin, Kristine H., Hansen, Tue H, Heggie, Alison, Hong, Mun-Gwan, Elders, Petra J M, Kennedy, Gwen, Kokkola, Tarja, Pedersen, Helle Krogh, Mahajan, Anubha, McEvoy, Donna, Pattou, Francois, Raverdy, Violeta, Häussler, Ragna S, Sharma, Sapna, Thomsen, Henrik S, Vangipurapu, Jagadish, Vestergaard, Henrik, Adamski, Jerzy, Musholt, Petra B, Brage, Søren, Brunak, Søren, Dermitzakis, Emmanouil, Frost, Gary, Hansen, Torben, Laakso, Markku, and Pedersen, Oluf

Abstract

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning.METHODS AND FINDINGS: We utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n = 795) or at high risk of developing the disease (n = 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (CONCLUSIONS: In this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see: https://www.predictliverfat.org/) and made it available to the community.TRIAL REGISTRATION: ClinicalTrials.gov NCT03814915.

Published
2020

50. Additional file 2 of Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

Author

Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, Masi, Federico De, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Ramneek Gupta, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Mun-Gwan Hong, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Anubha Mahajan, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstråle, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Jagadish Vangipurapu, Vestergaard, Henrik, Viñuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark I., Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Søren

Subjects
Data_FILES
Abstract

Additional file 2. Supplementary Methods. This file contains methods descriptions for omics data generation and preprocessing.

Published
2020
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