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3. Pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in individuals with type 2 diabetes.

Author

Pieber, Thomas R., Asong, Marisse, Fluhr, Gabriele, Höller, Vera, Kristensen, Niels R., Larsen, Jonas H., Ribel‐Madsen, Rasmus, Svehlikova, Eva, Vinther, Siri, Voortman, Margarete, and Haahr, Hanne

Subjects
TYPE 2 diabetes, INSULIN derivatives, PHARMACOKINETICS, INSULIN, GLUCOSE clamp technique, BODY mass index, BLOOD sugar
Abstract

Aims: To characterize the pharmacokinetic and pharmacodynamic properties of once‐weekly insulin icodec in type 2 diabetes (T2D). Materials and Methods: In an open‐label trial, 46 individuals with T2D (18‐75 years; body mass index 18.0‐38.0 kg/m2; glycated haemoglobin ≤75 mmol/mol [≤9%]; basal insulin‐treated) received subcutaneous once‐weekly icodec for ≥8 weeks at individualized doses, aiming at a pre‐breakfast plasma glucose concentration of 4.4 to 7.0 mmol/L (80‐126 mg/dL) on the last three mornings of each weekly dosing interval. Frequent blood sampling to assess total serum icodec concentration (ie, albumin‐bound and unbound) occurred from first icodec dose until 35 days after last dose. Icodec trough concentrations following initiation of once‐weekly dosing were predicted by pharmacokinetic modelling. During the final 3 weeks of icodec treatment, while at steady state, the icodec glucose‐lowering effect was assessed in three glucose clamps (target 7.5 mmol/L [135 mg/dL]): 0 to 36, 40 to 64 and 144 to 168 h post‐dose, thus covering the initial, middle and last part of the 1‐week dosing interval. Glucose‐lowering effect during a complete dosing interval was predicted by pharmacokinetic‐pharmacodynamic modelling. Results: Model‐predicted icodec steady state was attained after 3 to 4 weeks. At steady state, model‐predicted daily proportions of glucose‐lowering effect on days 1 to 7 of the 1‐week dosing interval were 14.1%, 16.1%, 15.8%, 15.0%, 14.0%, 13.0% and 12.0%, respectively. Icodec duration of action was at least 1 week in all participants. Once‐weekly icodec was overall safe and well tolerated in the current trial. Conclusions: The pharmacokinetic and pharmacodynamic characteristics of icodec in individuals with T2D support its potential as a once‐weekly basal insulin. [ABSTRACT FROM AUTHOR]

Published
2023
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9. Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing

Author

Nishimura, Erica, primary, Pridal, Lone, additional, Glendorf, Tine, additional, Hansen, Bo Falk, additional, Hubálek, František, additional, Kjeldsen, Thomas, additional, Kristensen, Niels Rode, additional, Lützen, Anne, additional, Lyby, Karsten, additional, Madsen, Peter, additional, Pedersen, Thomas Åskov, additional, Ribel-Madsen, Rasmus, additional, Stidsen, Carsten Enggaard, additional, and Haahr, Hanne, additional

Published
2021
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11. Altered DNA Methylation and Differential Expression of Genes Influencing Metabolism and Inflammation in Adipose Tissue From Subjects With Type 2 Diabetes

Author

Nilsson, Emma, Jansson, Per Anders, Perfilyev, Alexander, Volkov, Petr, Pedersen, Maria, Svensson, Maria K., Poulsen, Pernille, Ribel-Madsen, Rasmus, Pedersen, Nancy L., Almgren, Peter, Fadista, João, Rönn, Tina, Klarlund Pedersen, Bente, Scheele, Camilla, Vaag, Allan, and Ling, Charlotte

Published
2014
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12. Genetic risk score of 46 type 2 diabetes risk variants associates with changes in plasma glucose and estimates of pancreatic β-cell function over 5 years of follow-up

Author

Andersson, Ehm A., Allin, Kristine H., Sandholt, Camilla H., Borglykke, Anders, Lau, Cathrine J., Ribel-Madsen, Rasmus, Sparso, Thomas, Justesen, Johanne M., Harder, Marie N., Jorgensen, Marit E., Jorgensen, Torben, Hansen, Torben, and Pedersen, Oluf

Subjects
Pancreatic beta cells -- Physiological aspects, Glucose metabolism -- Physiological aspects, Type 2 diabetes -- Risk factors -- Genetic aspects, Health
Abstract

More than 40 genetic risk variants for type 2 diabetes have been validated. We aimed to test whether a genetic risk score associates with the incidence of type 2 diabetes and with 5-year changes in glycemic traits and whether the effects were modulated by changes in BMI and lifestyle. The Inter99 study population was genotyped for 46 variants, and a genetic risk score was constructed. During a median follow-up of 11 years, 327 of 5,850 individuals developed diabetes. Physical examinations and oral glucose tolerance tests were performed at baseline and after 5 years (n = 3,727). The risk of incident type 2 diabetes was increased with a hazard ratio of 1.06 (95% CI 1.03-1.08) per risk allele. While the population in general had improved glucose regulation during the 5-year follow-up period, each additional allele in the genetic risk score was associated with a relative increase in fasting, 30-min, and 120-min plasma glucose values and a relative decrease in measures of β-cell function over the 5-year period, whereas indices of insulin sensitivity were unaffected. The effect of the genetic risk score on 5-year changes in fasting plasma glucose was stronger in individuals who increased their BMI. In conclusion, a genetic risk score based on 46 variants associated strongly with incident type 2 diabetes and 5-year changes in plasma glucose and β-cell function. Individuals who gain weight may be more susceptible to the cumulative impact of type 2 diabetes risk variants on fasting plasma glucose., Type 2 diabetes is a complex metabolic disorder where both environment and genetic disposition act in concert to cause the disease. Over the last few years, genome-wide association studies and [...]

Published
2013
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13. Genetic and metabolic effects on skeletal muscle AMPK in young and older twins

Author

Mortensen, Brynjulf, Poulsen, Pernille, Wegner, Lise, Stender-Petersen, Kirstine L., Ribel-Madsen, Rasmus, Friedrichsen, Martin, Birk, Jesper B., Vaag, Allan, and Wojtaszewski, Jorgen F.P.

Subjects
Glycogen -- Analysis, Dextrose -- Analysis, Glucose -- Analysis, Type 2 diabetes -- Analysis, Glucose metabolism -- Analysis, RNA -- Analysis, Twins -- Analysis, Glycogen -- Synthesis, Biological sciences
Abstract

The protein complex AMP-activated protein kinase (AMPK) is believed to play an important role in the regulation of skeletal muscle glucose and lipid metabolism. Defects in the AMPK system might therefore be an important factor in the pathogenesis of type 2 diabetes. We aimed to identify genetic and environmental mechanisms involved in the regulation of AMPK expression and activity and to examine the association between AMPK protein levels and activity on the one hand, and glucose and fat metabolism on the other. We investigated skeletal muscle biopsies from 100 young and 82 older mono- and dizygotic nondiabetic twins excised during the basal and insulin-stimulated states of a physiological hyperinsulinemiceuglycemic clamp. AMPK[alpha]1, -[alpha]2, and -[gamma]3 mRNA expression was investigated using real-time PCR, and Western blotting was employed to measure protein levels. Multiple regression analyses indicated that skeletal muscle AMPK mRNA and protein expression as well as activity were regulated by sex, age, obesity, and aerobic capacity. Comparison of intraclass correlations on AMPK measurements from mono- and dizygotic twins suggested that skeletal muscle AMPK expression was under minor genetic influence. AMPK[gamma]3 protein expression and activity were negatively related to whole body glucose uptake through the nonoxidative metabolic pathway and positively related to phosphorylation of glycogen synthase. Our results suggest that skeletal muscle AMPK expression is under minor genetic control but regulated by age and sex and associated with obesity and aerobic capacity. Furthermore, our results indicate a role for [gamma]3-containing AMPK complexes in downregulation of insulin-stimulated nonoxidarive glucose metabolism possibly through inhibition of glycogen synthase activity. 5'-adenosine monophosphate-activated protein kinase; heritability; glucose metabolism doi: 10.1152/ajpendo.00058.2009

Published
2009

22. Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Author

Kraja, Aldi T, Liu, Chunyu, Fetterman, Jessica L, Graff, Mariaelisa, Have, Christian Theil, Gu, Charles, Yanek, Lisa R, Feitosa, Mary F, Arking, Dan E, Chasman, Daniel I, Young, Kristin, Ligthart, Symen, Hill, W David, Weiss, Stefan, Luan, Jian'an, Giulianini, Franco, Li-Gao, Ruifang, Hartwig, Fernando P, Lin, Shiow J, Wang, Lihua, Richardson, Tom G, Yao, Jie, Fernandez, Eliana P, Ghanbari, Mohsen, Wojczynski, Mary K, Lee, Wen-Jane, Argos, Maria, Armasu, Sebastian M, Barve, Ruteja A, Ryan, Kathleen A, An, Ping, Baranski, Thomas J, Bielinski, Suzette J, Bowden, Donald W, Broeckel, Ulrich, Christensen, Kaare, Chu, Audrey Y, Corley, Janie, Cox, Simon R, Uitterlinden, Andre G, Rivadeneira, Fernando, Cropp, Cheryl D, Daw, E Warwick, Van Heemst, Diana, De Las Fuentes, Lisa, Gao, He, Tzoulaki, Ioanna, Ahluwalia, Tarunveer S, De Mutsert, Renée, Emery, Leslie S, Erzurumluoglu, A Mesut, Perry, James A, Fu, Mao, Forouhi, Nita G, Gu, Zhenglong, Hai, Yang, Harris, Sarah E, Hemani, Gibran, Hunt, Steven C, Irvin, Marguerite R, Jonsson, Anna E, Justice, Anne E, Kerrison, Nicola D, Larson, Nicholas B, Lin, Keng-Hung, Love-Gregory, Latisha D, Mathias, Rasika A, Lee, Joseph H, Nauck, Matthias, Noordam, Raymond, Ong, Ken K, Pankow, James, Patki, Amit, Pattie, Alison, Petersmann, Astrid, Qi, Qibin, Ribel-Madsen, Rasmus, Rohde, Rebecca, Sandow, Kevin, Schnurr, Theresia M, Sofer, Tamar, Starr, John M, Taylor, Adele M, Teumer, Alexander, Timpson, Nicholas J, De Haan, Hugoline G, Wang, Yujie, Weeke, Peter E, Williams, Christine, Wu, Hongsheng, Yang, Wei, Zeng, Donglin, Witte, Daniel R, Weir, Bruce S, Wareham, Nicholas J, Vestergaard, Henrik, Turner, Stephen T, Torp-Pedersen, Christian, Stergiakouli, Evie, Sheu, Wayne Huey-Herng, Rosendaal, Frits R, Ikram, M Arfan, Franco, Oscar H, Ridker, Paul M, Perls, Thomas T, Pedersen, Oluf, Nohr, Ellen A, Newman, Anne B, Linneberg, Allan, Langenberg, Claudia, Kilpeläinen, Tuomas O, Kardia, Sharon LR, Jørgensen, Marit E, Jørgensen, Torben, Sørensen, Thorkild IA, Homuth, Georg, Hansen, Torben, Goodarzi, Mark O, Deary, Ian J, Christensen, Cramer, Chen, Yii-Der Ida, Chakravarti, Aravinda, Brandslund, Ivan, Bonnelykke, Klaus, Taylor, Kent D, Wilson, James G, Rodriguez, Santiago, Davies, Gail, Horta, Bernardo L, Thyagarajan, Bharat, Rao, DC, Grarup, Niels, Davila-Roman, Victor G, Hudson, Gavin, Guo, Xiuqing, Arnett, Donna K, Hayward, Caroline, Vaidya, Dhananjay, Mook-Kanamori, Dennis O, Tiwari, Hemant K, Levy, Daniel, Loos, Ruth JF, Dehghan, Abbas, Elliott, Paul, Malik, Afshan N, Scott, Robert A, Becker, Diane M, De Andrade, Mariza, Province, Michael A, Meigs, James B, Rotter, Jerome I, North, Kari E, Epidemiology, Internal Medicine, Gastroenterology & Hepatology, Home Office, Medical Research Council (MRC), National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, UK DRI Ltd, Luan, Jian'an [0000-0003-3137-6337], Erzurumluoglu, Mesut [0000-0003-1322-8138], Forouhi, Nita [0000-0002-5041-248X], Ong, Kenneth [0000-0003-4689-7530], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository

Subjects
insulin, HbA1c, MT-nDNA candidate genes, SUSCEPTIBILITY LOCI, Quantitative Trait Loci, 610 Medicine & health, ATHEROSCLEROSIS RISK, waist-to-hip ratio, PERIPHERAL-BLOOD, DNA, Mitochondrial, Article, HOMA-IR, Body Mass Index, Cohort Studies, BMI, 360 Social problems & social services, Adipocytes, Diabetes Mellitus, GLYCEMIC TRAITS, Humans, INDIVIDUALS REVEAL, GENOME-WIDE ASSOCIATION, glucose, Glycated Hemoglobin, Genetics & Heredity, Science & Technology, Waist-Hip Ratio, mtDNA, Genetic Variation, COMMON VARIANTS, HOMA-B, 11 Medical And Health Sciences, DNA COPY NUMBER, 06 Biological Sciences, BODY-MASS INDEX, mitochondria, Genes, Mitochondrial, Metabolism, ADIPOSE-TISSUE, Cardiovascular Diseases, Life Sciences & Biomedicine
Abstract

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E-04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E-03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E-06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.

Published
2019

23. Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men

Author

Broholm, Christa, primary, Ribel-Madsen, Rasmus, additional, Hjort, Line, additional, Olsson, Anders Henrik, additional, Ahlers, Juliane Maria Dorothee, additional, Hansen, Ninna Schiøler, additional, Schrölkamp, Maren, additional, Gillberg, Linn, additional, Perfilyev, Alexander, additional, Volkov, Petr, additional, Ling, Charlotte, additional, Jørgensen, Sine W., additional, Mortensen, Brynjulf, additional, Hingst, Janne, additional, Wojtaszewski, Jørgen, additional, Scheele, Camilla, additional, Brøns, Charlotte, additional, Pedersen, Bente Klarlund, additional, and Vaag, Allan, additional

Published
2019
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24. PPARG Pro12Ala Ala carriers exhibit greater improvements in peripheral insulin sensitivity in response to 12 weeks of aerobic exercise training

Author

Blond, Martin Bæk, primary, Schnurr, Theresia Maria, additional, Rosenkilde, Mads, additional, Quist, Jonas Salling, additional, Gram, Anne Sofie, additional, Reichkendler, Michala Holm, additional, Auerbach, Pernille Landrock, additional, Nordby, Pernille, additional, Skovgaard, Lene Theil, additional, Ribel-Madsen, Rasmus, additional, Justesen, Johanne Marie, additional, Kilpeläinen, Tuomas Oskari, additional, Ploug, Thorkil, additional, Stallknecht, Bente Merete, additional, and Hansen, Torben, additional

Published
2019
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26. ADAMTS9 Regulates Skeletal Muscle Insulin Sensitivity Through Extracellular Matrix Alterations

Author

Graae, Anne-Sofie, primary, Grarup, Niels, additional, Ribel-Madsen, Rasmus, additional, Lystbæk, Sara H., additional, Boesgaard, Trine, additional, Staiger, Harald, additional, Fritsche, Andreas, additional, Wellner, Niels, additional, Sulek, Karolina, additional, Kjolby, Mads, additional, Backe, Marie Balslev, additional, Chubanava, Sabina, additional, Prats, Clara, additional, Serup, Annette K., additional, Birk, Jesper B., additional, Dubail, Johanne, additional, Gillberg, Linn, additional, Vienberg, Sara G., additional, Nykjær, Anders, additional, Kiens, Bente, additional, Wojtaszewski, Jørgen F.P., additional, Larsen, Steen, additional, Apte, Suneel S., additional, Häring, Hans-Ulrich, additional, Vaag, Allan, additional, Zethelius, Björn, additional, Pedersen, Oluf, additional, Treebak, Jonas T., additional, Hansen, Torben, additional, and Holst, Birgitte, additional

Published
2019
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28. Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men.

Author

Broholm, Christa, Ribel-Madsen, Rasmus, Hjort, Line, Olsson, Anders Henrik, Ahlers, Juliane Maria Dorothee, Hansen, Ninna Schiøler, Schrölkamp, Maren, Gillberg, Linn, Perfilyev, Alexander, Volkov, Petr, Ling, Charlotte, Jørgensen, Sine W., Mortensen, Brynjulf, Hingst, Janne, Wojtaszewski, Jørgen, Scheele, Camilla, Brøns, Charlotte, Pedersen, Bente Klarlund, and Vaag, Allan

Subjects
*LOW birth weight, *MUSCLE cells, *STEM cells, *PROGENITOR cells, *TYPE 2 diabetes, *HISTONE deacetylase inhibitors, *MYOBLASTS
Abstract

Background: Being born with low birth weight (LBW) is a risk factor for muscle insulin resistance and type 2 diabetes (T2D), which may be mediated by epigenetic mechanisms programmed by the intrauterine environment. Epigenetic mechanisms exert their prime effects in developing cells. We hypothesized that muscle insulin resistance in LBW subjects may be due to early differential epigenomic and transcriptomic alterations in their immature muscle progenitor cells. Results: Muscle progenitor cells were obtained from 23 healthy young adult men born at term with LBW, and 15 BMI-matched normal birth weight (NBW) controls. The cells were subsequently cultured and differentiated into myotubes. DNA and RNA were harvested before and after differentiation for genome-wide DNA methylation and RNA expression measurements. After correcting for multiple comparisons (q ≤ 0.05), 56 CpG sites were found to be significantly, differentially methylated in myoblasts from LBW compared with NBW men, of which the top five gene-annotated CpG sites (SKI, ARMCX3, NR5A2, NEUROG, ESRRG) previously have been associated to regulation of cholesterol, fatty acid and glucose metabolism and muscle development or hypertrophy. LBW men displayed markedly decreased myotube gene expression levels of the AMPK-repressing tyrosine kinase gene FYN and the histone deacetylase gene HDAC7. Silencing of FYN and HDAC7 was associated with impaired myotube formation, which for HDAC7 reduced muscle glucose uptake. Conclusions: The data provides evidence of impaired muscle development predisposing LBW individuals to T2D is linked to and potentially caused by distinct DNA methylation and transcriptional changes including down regulation of HDAC7 and FYN in their immature myoblast stem cells. [ABSTRACT FROM AUTHOR]

Published
2020
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30. Additional file 2: Figure S1. of DNA methylation and gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance

Author

Main, Ailsa, Gillberg, Linn, Jacobsen, Anna, Nilsson, Emma, Gjesing, Anette, Hansen, Torben, Pedersen, Oluf, Ribel-Madsen, Rasmus, and Vaag, Allan

Subjects
body regions, nervous system, fungi
Abstract

Correlation between HIF3A DNA methylation levels at CpG sites 1 to 4 in blood. (PDF 67Â kb)

Published
2016
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31. Additional file 3: Figure S2. of DNA methylation and gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance

Author

Main, Ailsa, Gillberg, Linn, Jacobsen, Anna, Nilsson, Emma, Gjesing, Anette, Hansen, Torben, Pedersen, Oluf, Ribel-Madsen, Rasmus, and Vaag, Allan

Subjects
body regions, nervous system, fungi
Abstract

Correlation between HIF3A DNA methylation levels at CpG sites 1 to 4 in subcutaneous adipose tissue. (PDF 126Â kb)

Published
2016
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32. Additional file 4: Table S2. of DNA methylation and gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance

Author

Main, Ailsa, Gillberg, Linn, Jacobsen, Anna, Nilsson, Emma, Gjesing, Anette, Hansen, Torben, Pedersen, Oluf, Ribel-Madsen, Rasmus, and Vaag, Allan

Subjects
body regions, nervous system, fungi
Abstract

Associations between HIF3A DNA methylation levels in blood and subcutaneous adipose tissue. (PDF 175Â kb)

Published
2016
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33. Additional file 1: Table S1. of DNA methylation and gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance

Author

Main, Ailsa, Gillberg, Linn, Jacobsen, Anna, Nilsson, Emma, Gjesing, Anette, Hansen, Torben, Pedersen, Oluf, Ribel-Madsen, Rasmus, and Vaag, Allan

Subjects
body regions, nervous system, fungi
Abstract

Total number of samples (n) with HIF3A DNA methylation and gene expression data after quality control. (PDF 374Â kb)

Published
2016
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34. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author

Winkler, Thomas W., Justice, Anne E., Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F., Chu, Su, Czajkowski, Jacek, Esko, Tõnu, Fall, Tove, Kilpeläinen, Tuomas O., Lu, Yingchang, Mägi, Reedik, Mihailov, Evelin, Pers, Tune H., Rüeger, Sina, Teumer, Alexander, Ehret, Georg B., Ferreira, Teresa, Heard-Costa, Nancy L., Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D., Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M., Jansen, Rick, Westra, Harm-Jan, White, Charles C., Absher, Devin, Ahluwalia, Tarunveer S., Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L., de Craen, Anton J. M., Bis, Joshua C., Bonnefond, Amélie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston W. K., Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E., Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B., Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jackson, Anne U., Jacobs, Kevin B., Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E., Lahti, Jari, Leach, Irene Mateo, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela A. F., Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L., Montasser, May E., Müller, Gabriele, Müller-Nurasyid, Martina, Nolte, Ilja M., Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W., Renström, Frida, Rizzi, Federica, Rose, Lynda M., Ryan, Kathy A., Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stančáková, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J., Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P., Vandenput, Liesbeth, van der Laan, Sander W, van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L., Wang, Sophie R., Wang, Zhaoming, Wild, Sarah H., Willenborg, Christina, Wilson, James F., Wong, Andrew, Yang, Jian, Yengo, Loïc, Yerges-Armstrong, Laura M., Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A., Bakker, Stephan J. L., Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blüher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L., Boyd, Heather A., Bruinenberg, Marcel, Buchman, Aron S, Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S., Claudi-Boehm, Simone, Cole, John, Collins, Francis S., de Geus, Eco J. C., de Groot, Lisette C. P. G. M., Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G., Friedrich, Nele, Gejman, Pablo V., Gigante, Bruna, Glorioso, Nicola, Go, Alan S., Gottesman, Omri, Gräßler, Jürgen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C., Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T., Heath, Andrew C., Henders, Anjali K., Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G, Hui, Jennie, Husemoen, Lise L., Hutri-Kähönen, Nina, Hysi, Pirro G., Illig, Thomas, De Jager, Philip L., Jalilzadeh, Shapour, Jørgensen, Torben, Jukema, J. Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J., Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T., Kratzer, Wolfgang, Krüger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J., Leander, Karin, Lindström, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stéphane, Luben, Robert, Lyssenko, Valeriya, Männistö, Satu, Magnusson, Patrik K., McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W., Morris, Andrew P., Narisu, Narisu, Nelis, Mari, Ong, Ken K., Palotie, Aarno, Pérusse, Louis, Pichler, Irene, Pilia, Maria G., Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M., Rice, Treva K., Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R., Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Scott, William R., Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P. Eline, Smit, Jan H., Sparsø, Thomas H., Stirrups, Kathleen, Stolk, Ronald P., Stringham, Heather M., Swertz, Morris A, Swift, Amy J., Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J., Völker, Uwe, Vohl, Marie-Claude, Vonk, Judith M., Waldenberger, Melanie, Walker, Ryan W., Wennauer, Roman, Widén, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F., Zillikens, M. Carola, van Dijk, Suzanne C., van Schoor, Natasja M., Asselbergs, Folkert W., de Bakker, Paul I. W., Beckmann, Jacques S., Beilby, John, Bennett, David A., Bergman, Richard N., Bergmann, Sven, Böger, Carsten A., Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Chambers, John C., Chanock, Stephen J., Chasman, Daniel I., Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G., Evans, Denis A., de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W., Froguel, Philippe, Gansevoort, Ron T., Gieger, Christian, Grönberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliövaara, Markku, Hengstenberg, Christian, Hicks, Andrew A, Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V., Hveem, Kristian, James, Alan L., Jordan, Joanne M., Jula, Antti, Kähönen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus A. L. M., Kivimaki, Mika, Knekt, Paul B., Koistinen, Heikki A., Kooner, Jaspal S., Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G, Laakso, Markku, Lakka, Timo A., Lehtimäki, Terho, Lettre, Guillaume, Levinson, Douglas F., Lind, Lars, Lokki, Marja-Liisa, Mäntyselkä, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D., Moll, Frans L., Murray, Jeffrey C., Musk, Arthur W., Nieminen, Markku S., Njølstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Oostra, Ben A., Palmer, Lyle J, Pankow, James S., Pasterkamp, Gerard, Pedersen, Nancy L., Pedersen, Oluf, Penninx, Brenda W., Perola, Markus, Peters, Annette, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Qi, Lu, Quertermous, Thomas, Raitakari, Olli T., Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M., Rioux, John D., Rivadeneira, Fernando, Rotter, Jerome I., Rudan, Igor, den Ruijter, Hester M., Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter E. H., Shuldiner, Alan R., Sinisalo, Juha, Snieder, Harold, Sørensen, Thorkild I. A., Spector, Tim D., Staessen, Jan A., Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, Verbeek, André L. M., Vermeulen, Sita H., Viikari, Jorma S., Vitart, Veronique, Völzke, Henry, Vollenweider, Peter, Waeber, Gérard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Zeggini, Eleftheria, Chakravarti, Aravinda, Clegg, Deborah J., Cupples, L. Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E., Rao, D. C., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Inês, Berndt, Sonja I., Boehnke, Michael, Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Hunter, David J., Ingelsson, Erik, Kaplan, Robert C., McCarthy, Mark I., Mohlke, Karen L., O'Connell, Jeffrey R., Schlessinger, David, Strachan, David P., Stefansson, Kari, van Duijn, Cornelia M., Hirschhorn, Joel N., Lindgren, Cecilia M., Heid, Iris M., North, Kari E., Borecki, Ingrid B., Kutalik, Zoltán, and Loos, Ruth J. F.

Subjects
ddc
Published
2015

36. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Ried, Janina S., primary, Jeff M., Janina, additional, Chu, Audrey Y., additional, Bragg-Gresham, Jennifer L., additional, van Dongen, Jenny, additional, Huffman, Jennifer E., additional, Ahluwalia, Tarunveer S., additional, Cadby, Gemma, additional, Eklund, Niina, additional, Eriksson, Joel, additional, Esko, Tõnu, additional, Feitosa, Mary F., additional, Goel, Anuj, additional, Gorski, Mathias, additional, Hayward, Caroline, additional, Heard-Costa, Nancy L., additional, Jackson, Anne U., additional, Jokinen, Eero, additional, Kanoni, Stavroula, additional, Kristiansson, Kati, additional, Kutalik, Zoltán, additional, Lahti, Jari, additional, Luan, Jian'an, additional, Mägi, Reedik, additional, Mahajan, Anubha, additional, Mangino, Massimo, additional, Medina-Gomez, Carolina, additional, Monda, Keri L., additional, Nolte, Ilja M., additional, Pérusse, Louis, additional, Prokopenko, Inga, additional, Qi, Lu, additional, Rose, Lynda M., additional, Salvi, Erika, additional, Smith, Megan T., additional, Snieder, Harold, additional, Stančáková, Alena, additional, Ju Sung, Yun, additional, Tachmazidou, Ioanna, additional, Teumer, Alexander, additional, Thorleifsson, Gudmar, additional, van der Harst, Pim, additional, Walker, Ryan W., additional, Wang, Sophie R., additional, Wild, Sarah H., additional, Willems, Sara M., additional, Wong, Andrew, additional, Zhang, Weihua, additional, Albrecht, Eva, additional, Couto Alves, Alexessander, additional, Bakker, Stephan J. L., additional, Barlassina, Cristina, additional, Bartz, Traci M., additional, Beilby, John, additional, Bellis, Claire, additional, Bergman, Richard N., additional, Bergmann, Sven, additional, Blangero, John, additional, Blüher, Matthias, additional, Boerwinkle, Eric, additional, Bonnycastle, Lori L., additional, Bornstein, Stefan R., additional, Bruinenberg, Marcel, additional, Campbell, Harry, additional, Chen, Yii-Der Ida, additional, Chiang, Charleston W. K., additional, Chines, Peter S., additional, Collins, Francis S, additional, Cucca, Fracensco, additional, Cupples, L Adrienne, additional, D’Avila, Francesca, additional, de Geus, Eco J .C., additional, Dedoussis, George, additional, Dimitriou, Maria, additional, Döring, Angela, additional, Eriksson, Johan G., additional, Farmaki, Aliki-Eleni, additional, Farrall, Martin, additional, Ferreira, Teresa, additional, Fischer, Krista, additional, Forouhi, Nita G., additional, Friedrich, Nele, additional, Gjesing, Anette Prior, additional, Glorioso, Nicola, additional, Graff, Mariaelisa, additional, Grallert, Harald, additional, Grarup, Niels, additional, Gräßler, Jürgen, additional, Grewal, Jagvir, additional, Hamsten, Anders, additional, Harder, Marie Neergaard, additional, Hartman, Catharina A., additional, Hassinen, Maija, additional, Hastie, Nicholas, additional, Hattersley, Andrew Tym, additional, Havulinna, Aki S., additional, Heliövaara, Markku, additional, Hillege, Hans, additional, Hofman, Albert, additional, Holmen, Oddgeir, additional, Homuth, Georg, additional, Hottenga, Jouke-Jan, additional, Hui, Jennie, additional, Husemoen, Lise Lotte, additional, Hysi, Pirro G., additional, Isaacs, Aaron, additional, Ittermann, Till, additional, Jalilzadeh, Shapour, additional, James, Alan L., additional, Jørgensen, Torben, additional, Jousilahti, Pekka, additional, Jula, Antti, additional, Marie Justesen, Johanne, additional, Justice, Anne E., additional, Kähönen, Mika, additional, Karaleftheri, Maria, additional, Tee Khaw, Kay, additional, Keinanen-Kiukaanniemi, Sirkka M., additional, Kinnunen, Leena, additional, Knekt, Paul B., additional, Koistinen, Heikki A., additional, Kolcic, Ivana, additional, Kooner, Ishminder K., additional, Koskinen, Seppo, additional, Kovacs, Peter, additional, Kyriakou, Theodosios, additional, Laitinen, Tomi, additional, Langenberg, Claudia, additional, Lewin, Alexandra M., additional, Lichtner, Peter, additional, Lindgren, Cecilia M., additional, Lindström, Jaana, additional, Linneberg, Allan, additional, Lorbeer, Roberto, additional, Lorentzon, Mattias, additional, Luben, Robert, additional, Lyssenko, Valeriya, additional, Männistö, Satu, additional, Manunta, Paolo, additional, Leach, Irene Mateo, additional, McArdle, Wendy L., additional, Mcknight, Barbara, additional, Mohlke, Karen L., additional, Mihailov, Evelin, additional, Milani, Lili, additional, Mills, Rebecca, additional, Montasser, May E., additional, Morris, Andrew P., additional, Müller, Gabriele, additional, Musk, Arthur W., additional, Narisu, Narisu, additional, Ong, Ken K., additional, Oostra, Ben A., additional, Osmond, Clive, additional, Palotie, Aarno, additional, Pankow, James S., additional, Paternoster, Lavinia, additional, Penninx, Brenda W., additional, Pichler, Irene, additional, Pilia, Maria G., additional, Polašek, Ozren, additional, Pramstaller, Peter P., additional, Raitakari, Olli T, additional, Rankinen, Tuomo, additional, Rao, D. C., additional, Rayner, Nigel W., additional, Ribel-Madsen, Rasmus, additional, Rice, Treva K., additional, Richards, Marcus, additional, Ridker, Paul M., additional, Rivadeneira, Fernando, additional, Ryan, Kathy A., additional, Sanna, Serena, additional, Sarzynski, Mark A., additional, Scholtens, Salome, additional, Scott, Robert A., additional, Sebert, Sylvain, additional, Southam, Lorraine, additional, Sparsø, Thomas Hempel, additional, Steinthorsdottir, Valgerdur, additional, Stirrups, Kathleen, additional, Stolk, Ronald P., additional, Strauch, Konstantin, additional, Stringham, Heather M., additional, Swertz, Morris A., additional, Swift, Amy J., additional, Tönjes, Anke, additional, Tsafantakis, Emmanouil, additional, van der Most, Peter J., additional, Van Vliet-Ostaptchouk, Jana V., additional, Vandenput, Liesbeth, additional, Vartiainen, Erkki, additional, Venturini, Cristina, additional, Verweij, Niek, additional, Viikari, Jorma S., additional, Vitart, Veronique, additional, Vohl, Marie-Claude, additional, Vonk, Judith M., additional, Waeber, Gérard, additional, Widén, Elisabeth, additional, Willemsen, Gonneke, additional, Wilsgaard, Tom, additional, Winkler, Thomas W., additional, Wright, Alan F., additional, Yerges-Armstrong, Laura M., additional, Hua Zhao, Jing, additional, Carola Zillikens, M., additional, Boomsma, Dorret I., additional, Bouchard, Claude, additional, Chambers, John C., additional, Chasman, Daniel I., additional, Cusi, Daniele, additional, Gansevoort, Ron T., additional, Gieger, Christian, additional, Hansen, Torben, additional, Hicks, Andrew A., additional, Hu, Frank, additional, Hveem, Kristian, additional, Jarvelin, Marjo-Riitta, additional, Kajantie, Eero, additional, Kooner, Jaspal S., additional, Kuh, Diana, additional, Kuusisto, Johanna, additional, Laakso, Markku, additional, Lakka, Timo A., additional, Lehtimäki, Terho, additional, Metspalu, Andres, additional, Njølstad, Inger, additional, Ohlsson, Claes, additional, Oldehinkel, Albertine J., additional, Palmer, Lyle J., additional, Pedersen, Oluf, additional, Perola, Markus, additional, Peters, Annette, additional, Psaty, Bruce M., additional, Puolijoki, Hannu, additional, Rauramaa, Rainer, additional, Rudan, Igor, additional, Salomaa, Veikko, additional, Schwarz, Peter E. H., additional, Shudiner, Alan R., additional, Smit, Jan H., additional, Sørensen, Thorkild I. A., additional, Spector, Timothy D., additional, Stefansson, Kari, additional, Stumvoll, Michael, additional, Tremblay, Angelo, additional, Tuomilehto, Jaakko, additional, Uitterlinden, André G., additional, Uusitupa, Matti, additional, Völker, Uwe, additional, Vollenweider, Peter, additional, Wareham, Nicholas J., additional, Watkins, Hugh, additional, Wilson, James F., additional, Zeggini, Eleftheria, additional, Abecasis, Goncalo R., additional, Boehnke, Michael, additional, Borecki, Ingrid B., additional, Deloukas, Panos, additional, van Duijn, Cornelia M., additional, Fox, Caroline, additional, Groop, Leif C., additional, Heid, Iris M., additional, Hunter, David J., additional, Kaplan, Robert C., additional, McCarthy, Mark I., additional, North, Kari E., additional, O'Connell, Jeffrey R., additional, Schlessinger, David, additional, Thorsteinsdottir, Unnur, additional, Strachan, David P., additional, Frayling, Timothy, additional, Hirschhorn, Joel N., additional, Müller-Nurasyid, Martina, additional, and Loos, Ruth J. F., additional

Published
2016
Full Text
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37. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author

Winkler, Thomas W, Justice, Anne E, Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F, Chu, Su, Czajkowski, Jacek, Esko, Tõnu, Fall, Tove, Kilpeläinen, Tuomas O, Lu, Yingchang, Mägi, Reedik, Mihailov, Evelin, Pers, Tune H, Rüeger, Sina, Teumer, Alexander, Ehret, Georg B, Ferreira, Teresa, Heard-Costa, Nancy L, Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D, Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M, Jansen, Rick, Westra, Harm-Jan, White, Charles C, Absher, Devin, Ahluwalia, Tarunveer S, Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L, de Craen, Anton JM, Bis, Joshua C, Bonnefond, Amélie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston WK, Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E, Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B, Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E, Jackson, Anne U, Jacobs, Kevin B, Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E, Lahti, Jari, Mateo Leach, Irene, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela AF, Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L, Montasser, May E, Müller, Gabriele, Müller-Nurasyid, Martina, Nolte, Ilja M, Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W, Renström, Frida, Rizzi, Federica, Rose, Lynda M, Ryan, Kathy A, Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stančáková, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J, Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P, Vandenput, Liesbeth, van der Laan, Sander W, van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V, Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L, Wang, Sophie R, Wang, Zhaoming, Wild, Sarah H, Willenborg, Christina, Wilson, James F, Wong, Andrew, Yang, Jian, Yengo, Loïc, Yerges-Armstrong, Laura M, Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A, Bakker, Stephan JL, Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blüher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L, Boyd, Heather A, Bruinenberg, Marcel, Buchman, Aron S, Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S, Claudi-Boehm, Simone, Cole, John, Collins, Francis S, de Geus, Eco JC, de Groot, Lisette CPGM, Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G, Friedrich, Nele, Gejman, Pablo V, Gigante, Bruna, Glorioso, Nicola, Go, Alan S, Gottesman, Omri, Gräßler, Jürgen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T, Heath, Andrew C, Henders, Anjali K, Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G, Hui, Jennie, Husemoen, Lise L, Hutri-Kähönen, Nina, Hysi, Pirro G, Illig, Thomas, De Jager, Philip L, Jalilzadeh, Shapour, Jørgensen, Torben, Jukema, J Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J, Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T, Kratzer, Wolfgang, Krüger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J, Leander, Karin, Lindström, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stéphane, Luben, Robert, Lyssenko, Valeriya, Männistö, Satu, Magnusson, Patrik K, McArdle, Wendy L, Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W, Morris, Andrew P, Narisu, Narisu, Nelis, Mari, Ong, Ken K, Palotie, Aarno, Pérusse, Louis, Pichler, Irene, Pilia, Maria G, Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M, Rice, Treva K, Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R, Sarzynski, Mark A, Scholtens, Salome, Scott, Robert A, Scott, William R, Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P Eline, Smit, Jan H, Sparsø, Thomas H, Stirrups, Kathleen, Stolk, Ronald P, Stringham, Heather M, Swertz, Morris A, Swift, Amy J, Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J, Völker, Uwe, Vohl, Marie-Claude, Vonk, Judith M, Waldenberger, Melanie, Walker, Ryan W, Wennauer, Roman, Widén, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F, Zillikens, M Carola, van Dijk, Suzanne C, van Schoor, Natasja M, Asselbergs, Folkert W, de Bakker, Paul IW, Beckmann, Jacques S, Beilby, John, Bennett, David A, Bergman, Richard N, Bergmann, Sven, Böger, Carsten A, Boehm, Bernhard O, Boerwinkle, Eric, Boomsma, Dorret I, Bornstein, Stefan R, Bottinger, Erwin P, Bouchard, Claude, Chambers, John C, Chanock, Stephen J, Chasman, Daniel I, Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G, Evans, Denis A, de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W, Froguel, Philippe, Gansevoort, Ron T, Gieger, Christian, Grönberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliövaara, Markku, Hengstenberg, Christian, Hicks, Andrew A, Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V, Hveem, Kristian, James, Alan L, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus ALM, Kivimaki, Mika, Knekt, Paul B, Koistinen, Heikki A, Kooner, Jaspal S, Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G, Laakso, Markku, Lakka, Timo A, Lehtimäki, Terho, Lettre, Guillaume, Levinson, Douglas F, Lind, Lars, Lokki, Marja-Liisa, Mäntyselkä, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D, Moll, Frans L, Murray, Jeffrey C, Musk, Arthur W, Nieminen, Markku S, Njølstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J, Oostra, Ben A, Palmer, Lyle J, Pankow, James S, Pasterkamp, Gerard, Pedersen, Nancy L, Pedersen, Oluf, Penninx, Brenda W, Perola, Markus, Peters, Annette, Polašek, Ozren, Pramstaller, Peter P, Psaty, Bruce M, Qi, Lu, Quertermous, Thomas, Raitakari, Olli T, Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M, Rioux, John D, Rivadeneira, Fernando, Rotter, Jerome I, Rudan, Igor, den Ruijter, Hester M, Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter EH, Shuldiner, Alan R, Sinisalo, Juha, Snieder, Harold, Sørensen, Thorkild IA, Spector, Tim D, Staessen, Jan A, Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, André G, Uusitupa, Matti, Verbeek, André LM, Vermeulen, Sita H, Viikari, Jorma S, Vitart, Veronique, Völzke, Henry, Vollenweider, Peter, Waeber, Gérard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J, Watkins, Hugh, Zeggini, Eleftheria, arcOGEN Consortium, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Chakravarti, Aravinda, Clegg, Deborah J, Cupples, L Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E, Rao, DC, Abecasis, Goncalo R, Assimes, Themistocles L, Barroso, Inês, Berndt, Sonja I, Boehnke, Michael, Deloukas, Panos, Fox, Caroline S, Groop, Leif C, Hunter, David J, Ingelsson, Erik, Kaplan, Robert C, McCarthy, Mark I, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Hirschhorn, Joel N, Lindgren, Cecilia M, Heid, Iris M, North, Kari E, Borecki, Ingrid B, Kutalik, Zoltán, Loos, Ruth JF, Division of Statistical Genomics, Washington University School of Medicine, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Metabolic Science, MRC, Brown University, Center for Biological Sequence Analysis [Lyngby], Technical University of Denmark [Lyngby] (DTU), King‘s College London, Groningen Bioinformatics Centre, GBB, University of Groningen [Groningen], University of Queensland [Brisbane], National Institut of Food Science and Technology, University of Agriculture, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of neurology, Leiden University Medical Center (LUMC), University of Washington [Seattle], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Deptartment of Medical Biochemistry and Microbiology, Uppsala University, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Limnology, Ecology, Department of Ecology and Evolutionary Biology, University of California, Core Genotyping Facility, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Cancer Epidemiology and Genetics, Institute of Health Sciences and Biocenter Oulu, University of Oulu, Department of Chemical Engineering Taiwan (DCET - NTHU), National Tsing Hua University [Hsinchu] (NTHU), University of Oxford [Oxford], Department of Epidemiology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Departments of Epidemiology and Nutrition, Harvard School of Public Health, Department of Clinical Sciences, Lund University [Lund]-Lund University Diabetes Centre, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Department of Medical Sciences, Department of Educational Psychology and Counseling, National Taiwan Normal University (NTNU), Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE Genetics, deCODE genetics [Reykjavik], Interuniversity Cardiology Institute Netherlands, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Kidney Center, University Medical Center Groningen [Groningen] (UMCG), The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, TX], Medical Department III, Universität Leipzig [Leipzig], Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], GNS Science, Blackett Laboratory, Imperial College London, Medstar Research Institute, University of Rochester [USA], MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Dept Biochem & Mol Biol, Pennsylvania State University (Penn State), Penn State System-Penn State System, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Epidemiology, University Medical Centre Groningen, Unit for Molecular Epidemiology, German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Research Centre for Prevention and Health (RCPH), Department of Public Health [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Capital Region of Denmark, University of Copenhagen = Københavns Universitet (KU), Faculty of Medicine, Institute of Public Health, Aalborg University [Denmark] (AAU), Department of Nutrition-Dietetics, Harokopio University of Athens, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, MRC National Survey of Health and Development, MRC Unit for Lifelong Health and Ageing, Department of Epidemiology and Public Health, University College of London [London] (UCL), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Research Center for Prevention and Health, Glostrup Hospital, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Cambridge Institute of Public Health, University of Cambridge [UK] (CAM), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Queensland Institute of Medical Research, Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Head of Medical Sequencing, Department of Biostatistics, University of Washington, Department of Chronic Disease Prevention, Molecular Epidemiology, Department of Genetics, Université Laval [Québec] (ULaval), Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Department of Internal Medicine, Université de Lausanne (UNIL), Carl Gustav Carus University Hospital, Loughborough University, Genomics and Bioinformatics Platform, Fondazione Filarete, Department of Medicine, Surgery, and Dentistry, University of Milano, Medizinische Klinik II, Universität zu Lübeck [Lübeck], Department of Genomic Medicine, University of Manchester [Manchester], The Wellcome Trust Centre for Human Genetics [Oxford], National Institutes of Health [Bethesda] (NIH), Department of Nephrology, University Medical Center, University of Groningen, Helmholtz-Zentrum München (HZM), Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Genetics and Pathology, Department of child and adolescent psychiatry, Universität Duisburg-Essen [Essen], Department of Internal Medicine II, Division of Respirology, University of Regensburg, Regensburg, Germany, Universität Regensburg (UR), Franz-Volhard-Centrum für Klinische Forschung, ECRC, Department of Clinical Physiology, University of Tampere [Finland]-Tampere University Hospital, Finnish Institute of Occupational Health of Helsinki, Department of Clinical Chemistry, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Department of Oncology, University of Tampere Medical School, University of Tampere, Department of Physiology, University of Eastern Finland-Institute of Biomedicine, Department of Medicine, Montreal, Developmental Brain and Behaviour Unit, University of Southampton, Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Centre for Bone and Arthritis Research, Institute of Medicine-University of Gothenburg (GU), Interdisciplinary Center for Psychiatric Epidemiology, Experimental Cardiology Laboratory, University Medical Center [Utrecht], Peter MacCallum Cancer Center, Faculty of Health Sciences, Aarhus University [Aarhus], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Department of Health Services, University of Washington, Group Health Research Institute, Group Health Cooperative, Department of Epidemiology, University of Washington, Department of Medicine, University of Washington, Cardiovascular Health Research Unit, University of Washington, The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku University Hospital (TYKS), Erasmus Medical Centre, Cedars-Sinai Medical Center, Department of Pathological Biochemistry, Royal Infirmary, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Institute of Preventive Medicine, Copenhagen University Hospital-Bispebjerg and Frederiksberg Hospitals, Maastricht University [Maastricht], Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Epidemiology & Biostatistics, Radboud University Medical Center [Nijmegen], Institute for Community Medicine, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), MRC epidemiology Unit, Framingham Heart Study, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Metabolic Disease Group, University of Cambridge Metabolic Research Laboratories, Department of Genetics and Biotechnology, Wellcome Trust, Divisions of Genetics and Endocrinology and Program in Genomics, Boston Children's Hospital, Metabolism Initiative and Program in Medical and Population Genetics, Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Department of Medical Genetics, Epidemiology Unit, Addenbrooke's Hospital-Medical Research Council (MRC), P30 AG010161/AG/NIA NIH HHS/United States, Psychiatry, Epidemiology and Data Science, NCA - Neurobiology of mental health, EMGO - Lifestyle, overweight and diabetes, APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Other departments, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, RS: CARIM - R3 - Vascular biology, MUMC+: DA BV AIOS Radiologie (9), Epidemiologie, Orthopedie, Institute for Molecular Medicine Finland, Helsinki Collegium for Advanced Studies, Behavioural Sciences, University of Helsinki, Transplantation Laboratory, Medicum, Research Programs Unit, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Children's Hospital, Lastentautien yksikkö, Marja-Liisa Lokki / Principal Investigator, Kardiologian yksikkö, Leif Groop Research Group, Quantitative Genetics, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, Ehret, Georg Benedikt, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universiteit Leiden-Universiteit Leiden, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of California (UC), University of Oxford, Lund University [Lund], Universität Leipzig, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Capital Region of Denmark, University of Copenhagen = Københavns Universitet (UCPH), Université de Lausanne = University of Lausanne (UNIL), Universität zu Lübeck = University of Lübeck [Lübeck], Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Gothenburg (GU)-Institute of Medicine, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Luan, Jian'an [0000-0003-3137-6337], Tyrer, Jonathan [0000-0003-3724-4757], Forouhi, Nita [0000-0002-5041-248X], Khaw, Kay-Tee [0000-0002-8802-2903], Langenberg, Claudia [0000-0002-5017-7344], Luben, Robert [0000-0002-5088-6343], Ong, Kenneth [0000-0003-4689-7530], Johnson, Kathleen [0000-0002-6823-3252], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Apollo - University of Cambridge Repository, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Biochemistry, Surgery, Internal Medicine, Public Health, Medical Oncology, Pathology, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, and Clinical Genetics

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Male, Cancer Research, endocrine system diseases, Biological pathways, QH426-470, Genome, Body Mass Index, Body Size, Genetics (clinical), ddc:616, Genetics & Heredity, Sex Characteristics, Loci, MAGIC Consortium, Mass index, Age Factors, Chromosome Mapping, Middle Aged, Genealogy, Self-reported height, Peripheral-blood, Scale (social sciences), ICBP Consortium, Female, Life Sciences & Biomedicine, Medical Genetics, Research Article, arcOGEN Consortium, musculoskeletal diseases, Adult, European Continental Ancestry Group, Natural menopause, Aged, Body Size/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Biology, Body size, DIAGRAM Consortium, Age and sex, White People, Fat distribution, GLGC Consortium, 03 medical and health sciences, Life-course, Genetics, Weight-gain, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Medicinsk genetik, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0604 Genetics, Science & Technology, nutritional and metabolic diseases, Correction, 030104 developmental biology, GWAS meta-analysis, Global-BPGen Consortium, Common SNPS, CHARGE Consortium, 3111 Biomedicine, Developmental Biology
Abstract

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR, Author Summary Adult body size and body shape differ substantially between men and women and change over time. More than 100 genetic variants that influence body mass index (measure of body size) or waist-to-hip ratio (measure of body shape) have been identified. While there is evidence that some genetic loci affect body shape differently in men than in women, little is known about whether genetic effects differ in older compared to younger adults, and whether such changes differ between men and women. Therefore, we conducted a systematic genome-wide search, including 114 studies (>320,000 individuals), to specifically identify genetic loci with age- and or sex-dependent effects on body size and shape. We identified 15 loci of which the effect on BMI was different in older compared to younger adults, whereas we found no evidence for loci with different effects in men compared to women. The opposite was seen for body shape as we identified 44 loci of which the effect on waist-to-hip ratio differed between men and women, but no difference between younger and older adults were observed. Our observations may provide new insights into the biology that underlies weight change with age or the sexual dimorphism of body shape.

Published
2014

42. Akt2 influences glycogen synthase activity in human skeletal muscle through regulation of NH2-terminal (sites 2 + 2a) phosphorylation

Author

Friedrichsen, Martin, primary, Birk, Jesper B., additional, Richter, Erik A., additional, Ribel-Madsen, Rasmus, additional, Pehmøller, Christian, additional, Hansen, Bo Falck, additional, Beck-Nielsen, Henning, additional, Hirshman, Michael F., additional, Goodyear, Laurie J., additional, Vaag, Allan, additional, Poulsen, Pernille, additional, and Wojtaszewski, Jørgen F. P., additional

Published
2013
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44. Genome-Wide Analysis of DNA Methylation Differences in Muscle and Fat from Monozygotic Twins Discordant for Type 2 Diabetes

Author

Ribel-Madsen, Rasmus, primary, Fraga, Mario F., additional, Jacobsen, Stine, additional, Bork-Jensen, Jette, additional, Lara, Ester, additional, Calvanese, Vincenzo, additional, Fernandez, Agustin F., additional, Friedrichsen, Martin, additional, Vind, Birgitte F., additional, Højlund, Kurt, additional, Beck-Nielsen, Henning, additional, Esteller, Manel, additional, Vaag, Allan, additional, and Poulsen, Pernille, additional

Published
2012
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46. TheFOXO3Ars2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3AmRNA Expression in Twins

Author

Banasik, Karina, primary, Ribel-Madsen, Rasmus, additional, Gjesing, Anette P., additional, Wegner, Lise, additional, Andersson, Åsa, additional, Poulsen, Pernille, additional, Borglykke, Anders, additional, Witte, Daniel R., additional, Pedersen, Oluf, additional, Hansen, Torben, additional, and Vaag, Allan, additional

Published
2011
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48. Erratum: Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia

Author

Rung, Johan, primary, Cauchi, Stéphane, additional, Albrechtsen, Anders, additional, Shen, Lishuang, additional, Rocheleau, Ghislain, additional, Cavalcanti-Proença, Christine, additional, Bacot, François, additional, Balkau, Beverley, additional, Belisle, Alexandre, additional, Borch-Johnsen, Knut, additional, Charpentier, Guillaume, additional, Dina, Christian, additional, Durand, Emmanuelle, additional, Elliott, Paul, additional, Hadjadj, Samy, additional, Järvelin, Marjo-Riitta, additional, Laitinen, Jaana, additional, Lauritzen, Torsten, additional, Marre, Michel, additional, Mazur, Alexander, additional, Meyre, David, additional, Montpetit, Alexandre, additional, Pisinger, Charlotta, additional, Posner, Barry, additional, Poulsen, Pernille, additional, Pouta, Anneli, additional, Prentki, Marc, additional, Ribel-Madsen, Rasmus, additional, Ruokonen, Aimo, additional, Sandbaek, Anelli, additional, Serre, David, additional, Tichet, Jean, additional, Vaxillaire, Martine, additional, Wojtaszewski, Jørgen F P, additional, Vaag, Allan, additional, Hansen, Torben, additional, Polychronakos, Constantin, additional, Pedersen, Oluf, additional, Froguel, Philippe, additional, and Sladek, Robert, additional

Published
2009
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49. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia

Author

Rung, Johan, primary, Cauchi, Stéphane, additional, Albrechtsen, Anders, additional, Shen, Lishuang, additional, Rocheleau, Ghislain, additional, Cavalcanti-Proença, Christine, additional, Bacot, François, additional, Balkau, Beverley, additional, Belisle, Alexandre, additional, Borch-Johnsen, Knut, additional, Charpentier, Guillaume, additional, Dina, Christian, additional, Durand, Emmanuelle, additional, Elliott, Paul, additional, Hadjadj, Samy, additional, Järvelin, Marjo-Riitta, additional, Laitinen, Jaana, additional, Lauritzen, Torsten, additional, Marre, Michel, additional, Mazur, Alexander, additional, Meyre, David, additional, Montpetit, Alexandre, additional, Pisinger, Charlotta, additional, Posner, Barry, additional, Poulsen, Pernille, additional, Pouta, Anneli, additional, Prentki, Marc, additional, Ribel-Madsen, Rasmus, additional, Ruokonen, Aimo, additional, Sandbaek, Anelli, additional, Serre, David, additional, Tichet, Jean, additional, Vaxillaire, Martine, additional, Wojtaszewski, Jørgen F P, additional, Vaag, Allan, additional, Hansen, Torben, additional, Polychronakos, Constantin, additional, Pedersen, Oluf, additional, Froguel, Philippe, additional, and Sladek, Robert, additional

Published
2009
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50. Akt2 influences glycogen synthase activity in human skeletal muscle through regulation of NH2-terminal (sites 2 + 2a) phosphorylation.

Author

Friedrichsen, Martin, Birk, Jesper B., Richter, Erik A., Ribel-Madsen, Rasmus, Pehmøller, Christian, Hansen, Bo Falck, Beck-Nielsen, Henning, Hirshman, Michael F., Goodyear, Laurie J., Vaag, Allan, Poulsen, Pernille, and Wojtaszewski, Jørgen F. P.

Subjects
TYPE 2 diabetes, GLYCOGEN synthases, SKELETAL muscle
Abstract

Type 2 diabetes is characterized by reduced muscle glycogen synthesis. The key enzyme in this process, glycogen synthase (GS), is activated via proximal insulin signaling, but the exact molecular events remain unknown. Previously, we demonstrated that phosphorylation of Thr308 on Akt (p-Akt-Thr308), Akt2 activity, and GS activity in muscle were positively associated with insulin sensitivity. Here, in the same study population, we determined the influence of several upstream elements in the canonical PI3K signaling on muscle GS activation. One-hundred eighty-one nondiabetic twins were examined with the euglycemic hyperinsulinemic clamp combined with excision of muscle biopsies. Insulin signaling was evaluated at the levels of the insulin receptor, IRS-1-associated PI3K (IRS-1-PI3K), Akt, and GS employing activity assays and phosphospecific Western blotting. The insulin-stimulated GS activity was positively associated with p-Akt-Thr308 (P = 0.01) and Akt2 activity (P = 0.04) but not p-Akt-Ser473 or IRS-1-PI3K activity. Furthermore, p-Akt-Thr308 and Akt2 activity were negatively associated with NH2-terminal GS phosphorylation (P = 0.001 for both), which in turn was negatively associated with insulin-stimulated GS activity (P < 0.001). We found no association between COOH-terminal GS phosphorylation and Akt or GS activity. Employing whole body Akt2-knockout mice, we validated the necessity for Akt2 in insulin-mediated GS activation. However, since insulin did not affect NH2-terminal phosphorylation in mice, we could not use this model to validate the observed association between GS NH2-terminal phosphorylation and Akt activity in humans. In conclusion, our study suggests that although COOH-terminal dephosphorylation is likely necessary for GS activation, Akt2-dependent NH2-terminal dephosphorylation may be the site for "fine-tuning" insulin-mediated GS activation in humans. [ABSTRACT FROM AUTHOR]

Published
2013
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