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2. SMUG1 regulates fat homeostasis leading to a fatty liver phenotype in mice

Author

Carracedo, Sergio, Lirussi, Lisa, Alsøe, Lene, Segers, Filip, Wang, Changliang, Bartosova, Zdenka, Bohov, Pavol, Tekin, Nuriye B., Kong, Xiang Yi, Esbensen, Q. Ying, Chen, Liang, Wennerström, Anna, Kroustallaki, Penelope, Ceolotto, Deborah, Tönjes, Anke, Berge, Rolf Kristian, Bruheim, Per, Wong, Garry, Böttcher, Yvonne, Halvorsen, Bente, and Nilsen, Hilde

Published
2022
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4. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Locke, Adam E, Mägi, Reedik, Strawbridge, Rona J, Pers, Tune H, Fischer, Krista, Justice, Anne E, Workalemahu, Tsegaselassie, Wu, Joseph MW, Buchkovich, Martin L, Heard-Costa, Nancy L, Roman, Tamara S, Drong, Alexander W, Song, Ci, Gustafsson, Stefan, Day, Felix R, Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jian’an, Randall, Joshua C, Scherag, André, Vedantam, Sailaja, Wood, Andrew R, Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M, Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L, Buyske, Steven, Demirkan, Ayse, Ehret, Georg B, Feitosa, Mary F, Goel, Anuj, Jackson, Anne U, Johnson, Toby, Kleber, Marcus E, Kristiansson, Kati, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J, Prokopenko, Inga, Stančáková, Alena, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V, Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B, Caspersen, Ida H, Clarke, Robert, Warwick Daw, E, Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex SF, Eklund, Niina, Erdos, Michael R, Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S, Golay, Alain, Grallert, Harald, Grammer, Tanja B, Gräßler, Jürgen, Grewal, Jagvir, Groves, Christopher J, Haller, Toomas, and Hallmans, Goran

Subjects
Genetics, Human Genome, Diabetes, Obesity, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Cardiovascular, Stroke, Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Fat Distribution, Body Mass Index, Epigenesis, Genetic, Europe, Female, Genome, Human, Genome-Wide Association Study, Humans, Insulin, Insulin Resistance, Male, Models, Biological, Neovascularization, Physiologic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Racial Groups, Sex Characteristics, Transcription, Genetic, Waist-Hip Ratio, ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, GLGC, ICBP, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, General Science & Technology
Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P

Published
2015

5. Genetic studies of body mass index yield new insights for obesity biology

Author

Locke, Adam E, Kahali, Bratati, Berndt, Sonja I, Justice, Anne E, Pers, Tune H, Day, Felix R, Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L, Yang, Jian, Croteau-Chonka, Damien C, Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltán, Luan, Jian’an, Mägi, Reedik, Randall, Joshua C, Winkler, Thomas W, Wood, Andrew R, Workalemahu, Tsegaselassie, Faul, Jessica D, Smith, Jennifer A, Hua Zhao, Jing, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Åsa K, Karjalainen, Juha, Schmidt, Ellen M, Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L, Bragg-Gresham, Jennifer L, Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B, Feenstra, Bjarke, Feitosa, Mary F, Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U, Kanoni, Stavroula, Kleber, Marcus E, Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Medland, Sarah E, Nalls, Michael A, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J, Prokopenko, Inga, Shungin, Dmitry, Stančáková, Alena, Strawbridge, Rona J, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V, Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M, Attwood, Antony P, Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blagieva, Roza, Blüher, Matthias, Böhringer, Stefan, Bonnycastle, Lori L, Böttcher, Yvonne, Boyd, Heather A, Bruinenberg, Marcel, Caspersen, Ida H, Ida Chen, Yii-Der, Clarke, Robert, Warwick Daw, E, de Craen, Anton JM, Delgado, Graciela, and Dimitriou, Maria

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Nutrition, Obesity, Prevention, Aetiology, 2.1 Biological and endogenous factors, Stroke, Cardiovascular, Metabolic and endocrine, Oral and gastrointestinal, Cancer, Adipogenesis, Adiposity, Age Factors, Body Mass Index, Energy Metabolism, Europe, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Glutamic Acid, Humans, Insulin, Insulin Secretion, Male, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Racial Groups, Synapses, LifeLines Cohort Study, ADIPOGen Consortium, AGEN-BMI Working Group, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GLGC, ICBP, MAGIC Investigators, MuTHER Consortium, MIGen Consortium, PAGE Consortium, ReproGen Consortium, GENIE Consortium, International Endogene Consortium, General Science & Technology
Abstract

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Published
2015

6. Defining the role of common variation in the genomic and biological architecture of adult human height

Author

Wood, Andrew R, Esko, Tonu, Yang, Jian, Vedantam, Sailaja, Pers, Tune H, Gustafsson, Stefan, Chu, Audrey Y, Estrada, Karol, Luan, Jian'an, Kutalik, Zoltán, Amin, Najaf, Buchkovich, Martin L, Croteau-Chonka, Damien C, Day, Felix R, Duan, Yanan, Fall, Tove, Fehrmann, Rudolf, Ferreira, Teresa, Jackson, Anne U, Karjalainen, Juha, Lo, Ken Sin, Locke, Adam E, Mägi, Reedik, Mihailov, Evelin, Porcu, Eleonora, Randall, Joshua C, Scherag, André, Vinkhuyzen, Anna AE, Westra, Harm-Jan, Winkler, Thomas W, Workalemahu, Tsegaselassie, Zhao, Jing Hua, Absher, Devin, Albrecht, Eva, Anderson, Denise, Baron, Jeffrey, Beekman, Marian, Demirkan, Ayse, Ehret, Georg B, Feenstra, Bjarke, Feitosa, Mary F, Fischer, Krista, Fraser, Ross M, Goel, Anuj, Gong, Jian, Justice, Anne E, Kanoni, Stavroula, Kleber, Marcus E, Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Lui, Julian C, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Nalls, Michael A, Nyholt, Dale R, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Prokopenko, Inga, Ried, Janina S, Ripke, Stephan, Shungin, Dmitry, Stancáková, Alena, Strawbridge, Rona J, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V, Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Afzal, Uzma, Ärnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Bolton, Jennifer L, Böttcher, Yvonne, Boyd, Heather A, Bruinenberg, Marcel, Buckley, Brendan M, Buyske, Steven, Caspersen, Ida H, Chines, Peter S, Clarke, Robert, Claudi-Boehm, Simone, Cooper, Matthew, Daw, E Warwick, De Jong, Pim A, Deelen, Joris, and Delgado, Graciela

Subjects
Biological Sciences, Genetics, Biotechnology, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adult, Analysis of Variance, Body Height, Genetic Variation, Genetics, Population, Genome-Wide Association Study, Humans, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, White People, Electronic Medical Records and Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Published
2014

9. Impact of Type 2 Diabetes Susceptibility Variants on Quantitative Glycemic Traits Reveals Mechanistic Heterogeneity

Author

Dimas, Antigone S, Lagou, Vasiliki, Barker, Adam, Knowles, Joshua W, Mägi, Reedik, Hivert, Marie-France, Benazzo, Andrea, Rybin, Denis, Jackson, Anne U, Stringham, Heather M, Song, Ci, Fischer-Rosinsky, Antje, Boesgaard, Trine Welløv, Grarup, Niels, Abbasi, Fahim A, Assimes, Themistocles L, Hao, Ke, Yang, Xia, Lecoeur, Cécile, Barroso, Inês, Bonnycastle, Lori L, Böttcher, Yvonne, Bumpstead, Suzannah, Chines, Peter S, Erdos, Michael R, Graessler, Jurgen, Kovacs, Peter, Morken, Mario A, Narisu, Narisu, Payne, Felicity, Stancakova, Alena, Swift, Amy J, Tönjes, Anke, Bornstein, Stefan R, Cauchi, Stéphane, Froguel, Philippe, Meyre, David, Schwarz, Peter EH, Häring, Hans-Ulrich, Smith, Ulf, Boehnke, Michael, Bergman, Richard N, Collins, Francis S, Mohlke, Karen L, Tuomilehto, Jaakko, Quertemous, Thomas, Lind, Lars, Hansen, Torben, Pedersen, Oluf, Walker, Mark, Pfeiffer, Andreas FH, Spranger, Joachim, Stumvoll, Michael, Meigs, James B, Wareham, Nicholas J, Kuusisto, Johanna, Laakso, Markku, Langenberg, Claudia, Dupuis, Josée, Watanabe, Richard M, Florez, Jose C, Ingelsson, Erik, McCarthy, Mark I, Prokopenko, Inga, and Investigators, on behalf of the MAGIC

Subjects
Biomedical and Clinical Sciences, Genetics, Diabetes, Autoimmune Disease, Clinical Research, Prevention, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Alleles, Cluster Analysis, Diabetes Mellitus, Type 2, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Insulin, Insulin Resistance, Insulin Secretion, Insulin-Secreting Cells, Male, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, Transcription Factors, MAGIC Investigators, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.

Published
2014

11. Obesity Is Associated with Distorted Proteoglycan Expression in Adipose Tissue

Author

Meen, Astri J., primary, Doncheva, Atanaska I., additional, Böttcher, Yvonne, additional, Dankel, Simon N., additional, Hoffmann, Anne, additional, Blüher, Matthias, additional, Fernø, Johan, additional, Mellgren, Gunnar, additional, Ghosh, Adhideb, additional, Sun, Wenfei, additional, Dong, Hua, additional, Noé, Falko, additional, Wolfrum, Christian, additional, Pejler, Gunnar, additional, Dalen, Knut Tomas, additional, and Kolset, Svein O., additional

Published
2023
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14. Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity

Author

Keller, Maria, Hopp, Lydia, Liu, Xuanshi, Wohland, Tobias, Rohde, Kerstin, Cancello, Raffaella, Klös, Matthias, Bacos, Karl, Kern, Matthias, Eichelmann, Fabian, Dietrich, Arne, Schön, Michael R., Gärtner, Daniel, Lohmann, Tobias, Dreßler, Miriam, Stumvoll, Michael, Kovacs, Peter, DiBlasio, Anna-Maria, Ling, Charlotte, Binder, Hans, Blüher, Matthias, and Böttcher, Yvonne

Published
2017
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15. FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis

Author

Shamsi, Farnaz, Xue, Ruidan, Huang, Tian Lian, Lundh, Morten, Liu, Yang, Leiria, Luiz O., Lynes, Matthew D., Kempf, Elena, Wang, Chih-Hao, Sugimoto, Satoru, Nigro, Pasquale, Landgraf, Kathrin, Schulz, Tim, Li, Yiming, Emanuelli, Brice, Kothakota, Srinivas, Williams, Lewis T., Jessen, Niels, Pedersen, Steen Bønløkke, Böttcher, Yvonne, Blüher, Matthias, Körner, Antje, Goodyear, Laurie J., Mohammadi, Moosa, Kahn, C. Ronald, and Tseng, Yu-Hua

Published
2020
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19. DNA methylation patterns reflect individual's lifestyle independent of obesity

Author

Klemp, Ireen, primary, Hoffmann, Anne, additional, Müller, Luise, additional, Hagemann, Tobias, additional, Horn, Kathrin, additional, Rohde‐Zimmermann, Kerstin, additional, Tönjes, Anke, additional, Thiery, Joachim, additional, Löffler, Markus, additional, Burkhardt, Ralph, additional, Böttcher, Yvonne, additional, Stumvoll, Michael, additional, Blüher, Matthias, additional, Krohn, Knut, additional, Scholz, Markus, additional, Baber, Ronny, additional, Franks, Paul W, additional, Kovacs, Peter, additional, and Keller, Maria, additional

Published
2022
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21. The emergent role of mitochondrial RNA modifications in metabolic alterations

Author

Boughanem, Hatim, Böttcher, Yvonne, Tomé-Carneiro, João, López de las Hazas, María-Carmen, Dávalos, Akin Cayir, and Manuel, Macias-González

Subjects
Metabolismo, RNA modifications, Metabolic alterations, Metabolism, Epitranscriptomics, Mitochondria
Abstract

Mitochondrial epitranscriptomics refers to the modifications occurring in all the different RNA types of mitochondria. Although the number of mitochondrial RNA modifications is less than those in cytoplasm, substantial evidence indicates that they play a critical role in accurate protein synthesis. Recent evidence supported those modifications in mitochondrial RNAs also have crucial implications in mitochondrial-related diseases. In the light of current knowledge about the involvement, the association between mitochondrial RNA modifications and diseases arises from studies focusing on mutations in both mitochondrial and nuclear DNA genes encoding enzymes involved in such modifications. Here, we review the current evidence available for mitochondrial RNA modifications and their role in metabolic disorders, and we also explore the possibility of using them as promising targets for prevention and early detection. Finally, we discuss future directions of mitochondrial epitranscriptomics in these metabolic alterations, and how these RNA modifications may offer a new diagnostic and theragnostic avenue for preventive purposes. This work was supported by the European Cooperation in Science and Technology (COST) Action CA16120 (European Epitranscriptomic Network). This work was also supported by “Centros de Investigación En Red” (CIBER, CB06/03/0018) of the “Instituto de Salud Carlos III” (ISCIII) (PI18/01399), and co-financed by the European Regional Development Fund (FEDER). This work was also supported by the Agencia Estatal de Investigación and European FEDER Funds (PID2019-109369RB-100 and AGL2018-78922-R). HB is supported by a predoctoral fellowship (“Plan Propio IBIMA 2020 A.1 Contratos predoctorales”, Ref.: predoc20_002). M.M.G. was the recipient of the Nicolas Monardes Programme from the “Servicio Andaluz de Salud, Junta de Andalucia”, Spain (RC-0001-2018 and C-0029-2014). funding for open access charge: Universidad de Málaga

Published
2022

23. Serglycin Is Involved in Adipose Tissue Inflammation in Obesity

Author

Doncheva, Atanaska I., primary, Norheim, Frode A., additional, Hjorth, Marit, additional, Grujic, Mirjana, additional, Paivandy, Aida, additional, Dankel, Simon N., additional, Hertel, Jens Kristoffer, additional, Valderhaug, Tone G., additional, Böttcher, Yvonne, additional, Fernø, Johan, additional, Mellgren, Gunnar, additional, Dalen, Knut T., additional, Pejler, Gunnar, additional, and Kolset, Svein O., additional

Published
2022
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25. Maternal Glucose and LDL-Cholesterol Levels Are Related to Placental Leptin Gene Methylation, and, Together With Nutritional Factors, Largely Explain a Higher Methylation Level Among Ethnic South Asians

Author

Sletner, Line, primary, Moen, Aina E. F., additional, Yajnik, Chittaranjan S., additional, Lekanova, Nadezhda, additional, Sommer, Christine, additional, Birkeland, Kåre I., additional, Jenum, Anne K., additional, and Böttcher, Yvonne, additional

Published
2021
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28. 37 DNA methylation pattern in blood may reflect individuals’ daily lifestyle

Author

Klemp, Ireen, additional, Hoffmann, Anne, additional, Müller, Luise, additional, Hagemann, Tobias, additional, Rohde-Zimmermann, Kerstin, additional, Böttcher, Yvonne, additional, Stumvoll, Michael, additional, Blüher, Matthias, additional, Scholz, Markus, additional, Krohn, Knut, additional, Baber, Ronny, additional, Franks, PaulW., additional, Kovacs, Peter, additional, and Keller, Maria, additional

Published
2021
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33. Cohort profile: Epigenetics in Pregnancy (EPIPREG) – population-based sample of European and South Asian pregnant women with epigenome-wide DNA methylation (850k) in peripheral blood leukocytes

Author

Fragoso-Bargas, Nicolas, primary, Opsahl, Julia O., additional, Kiryushchenko, Nadezhda, additional, Böttcher, Yvonne, additional, Lee-Ødegård, Sindre, additional, Qvigstad, Elisabeth, additional, Richardsen, Kåre Rønn, additional, Waage, Christin W., additional, Sletner, Line, additional, Jenum, Anne Karen, additional, Prasad, Rashmi B., additional, Groop, Leif C., additional, Moen, Gunn-Helen, additional, Birkeland, Kåre I., additional, and Sommer, Christine, additional

Published
2021
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34. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Author

Wheeler, Eleanor, Leong, Aaron, Liu, Ching-Ti, Hivert, Marie-France, Strawbridge, Rona J., Podmore, Clara, Li, Man, Yao, Jie, Sim, Xueling, Hong, Jaeyoung, Chu, Audrey Y., Zhang, Weihua, Wang, Xu, Chen, Peng, Maruthur, Nisa M., Porneala, Bianca C., Sharp, Stephen J., Jia, Yucheng, Kabagambe, Edmond K., Chang, Li-Ching, Chen, Wei-Min, Elks, Cathy E., Evans, Daniel S., Fan, Qiao, Giulianini, Franco, Go, Min Jin, Hottenga, Jouke-Jan, Hu, Yao, Jackson, Anne U., Kanoni, Stavroula, Kim, Young Jin, Kleber, Marcus E., Ladenvall, Claes, Lecoeur, Cecile, Lim, Sing-Hui, Lu, Yingchang, Mahajan, Anubha, Marzi, Carola, Nalls, Mike A., Navarro, Pau, Nolte, Ilja M., Rose, Lynda M., Rybin, Denis V., Sanna, Serena, Shi, Yuan, Stram, Daniel O., Takeuchi, Fumihiko, Tan, Shu Pei, van der Most, Peter J., Van Vliet-Ostaptchouk, Jana V., Wong, Andrew, Yengo, Loic, Zhao, Wanting, Goel, Anuj, Martinez Larrad, Maria Teresa, Radke, Dörte, Salo, Perttu, Tanaka, Toshiko, van Iperen, Erik P. A., Abecasis, Goncalo, Afaq, Saima, Alizadeh, Behrooz Z., Bertoni, Alain G., Bonnefond, Amelie, Böttcher, Yvonne, Bottinger, Erwin P., Campbell, Harry, Carlson, Olga D., Chen, Chien-Hsiun, Cho, Yoon Shin, Garvey, W. Timothy, Gieger, Christian, Goodarzi, Mark O., Grallert, Harald, Hamsten, Anders, Hartman, Catharina A., Herder, Christian, Hsiung, Chao Agnes, Huang, Jie, Igase, Michiya, Isono, Masato, Katsuya, Tomohiro, Khor, Chiea-Chuen, Kiess, Wieland, Kohara, Katsuhiko, Kovacs, Peter, Lee, Juyoung, Lee, Wen-Jane, Lehne, Benjamin, Li, Huaixing, Liu, Jianjun, Lobbens, Stephane, Luan, Jian'an, Lyssenko, Valeriya, Meitinger, Thomas, Miki, Tetsuro, Miljkovic, Iva, Moon, Sanghoon, Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Nagaraja, Ramaiah, Nauck, Matthias, Pankow, James S., Polasek, Ozren, Prokopenko, Inga, Ramos, Paula S., Rasmussen-Torvik, Laura, Rathmann, Wolfgang, Rich, Stephen S., Robertson, Neil R., Roden, Michael, Roussel, Ronan, Rudan, Igor, Scott, Robert A., Scott, William R., Sennblad, Bengt, Siscovick, David S., Strauch, Konstantin, Sun, Liang, Swertz, Morris, Tajuddin, Salman M., Taylor, Kent D., Teo, Yik-Ying, Tham, Yih Chung, Tönjes, Anke, Wareham, Nicholas J., Willemsen, Gonneke, Wilsgaard, Tom, Hingorani, Aroon D., Egan, Josephine, Ferrucci, Luigi, Hovingh, G. Kees, Jula, Antti, Kivimaki, Mika, Kumari, Meena, Njølstad, Inger, Palmer, Colin N. A., Serrano Ríos, Manuel, Stumvoll, Michael, Watkins, Hugh, Aung, Tin, Blüher, Matthias, Boehnke, Michael, Boomsma, Dorret I., Bornstein, Stefan R., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Chen, Yduan-Tsong, Cheng, Ching-Yu, Cucca, Francesco, de Geus, Eco J. C., Deloukas, Panos, Evans, Michele K., Fornage, Myriam, Friedlander, Yechiel, Froguel, Philippe, Groop, Leif, Gross, Myron D., Harris, Tamara B., Hayward, Caroline, Heng, Chew-Kiat, Ingelsson, Erik, Kato, Norihiro, Kim, Bong-Jo, Koh, Woon-Puay, Kooner, Jaspal S., Körner, Antje, Kuh, Diana, Kuusisto, Johanna, Laakso, Markku, Lin, Xu, Liu, Yongmei, Loos, Ruth J. F., Magnusson, Patrik K. E., März, Winfried, McCarthy, Mark I., Oldehinkel, Albertine J., Ong, Ken K., Pedersen, Nancy L., Pereira, Mark A., Peters, Annette, Ridker, Paul M., Sabanayagam, Charumathi, Sale, Michele, Saleheen, Danish, Saltevo, Juha, Schwarz, Peter EH., Sheu, Wayne H. H., Snieder, Harold, Spector, Timothy D., Tabara, Yasuharu, Tuomilehto, Jaakko, van Dam, Rob M., Wilson, James G., Wilson, James F., Wolffenbuttel, Bruce H. R., Wong, Tien Yin, Wu, Jer-Yuarn, Yuan, Jian-Min, Zonderman, Alan B., Soranzo, Nicole, Guo, Xiuqing, Roberts, David J., Florez, Jose C., Sladek, Robert, Dupuis, Josée, Morris, Andrew P., Tai, E-Shyong, Selvin, Elizabeth, Rotter, Jerome I., Langenberg, Claudia, Barroso, Inês, and Meigs, James B.

Subjects
Genotypes -- Research, African Americans -- Analysis -- Health aspects, Type 2 diabetes -- Risk factors -- Diagnosis, Biological sciences
Abstract

Background Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. Methods & findings Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10.sup.-29 ); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. Conclusions As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses., Author(s): Eleanor Wheeler 1, Aaron Leong 2,3, Ching-Ti Liu 4, Marie-France Hivert 5,6, Rona J. Strawbridge 7,8, Clara Podmore 9,10, Man Li 11,12,13, Jie Yao 14, Xueling Sim 15, Jaeyoung [...]

Published
2017
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35. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Author

Manning, Alisa K, Hivert, Marie-France, Scott, Robert A, Grimsby, Jonna L, Bouatia-Naji, Nabila, Chen, Han, Rybin, Denis, Liu, Ching-Ti, Bielak, Lawrence F, Prokopenko, Inga, Amin, Najaf, Barnes, Daniel, Cadby, Gemma, Hottenga, Jouke-Jan, Ingelsson, Erik, Jackson, Anne U, Johnson, Toby, Kanoni, Stavroula, Ladenvall, Claes, Lagou, Vasiliki, Lahti, Jari, Lecoeur, Cecile, Liu, Yongmei, Martinez-Larrad, Maria Teresa, Montasser, May E, Navarro, Pau, Perry, John R B, Rasmussen-Torvik, Laura J, Salo, Perttu, Sattar, Naveed, Shungin, Dmitry, Strawbridge, Rona J, Tanaka, Toshiko, van Duijn, Cornelia M, An, Ping, de Andrade, Mariza, Andrews, Jeanette S, Aspelund, Thor, Atalay, Mustafa, Aulchenko, Yurii, Balkau, Beverley, Bandinelli, Stefania, Beckmann, Jacques S, Beilby, John P, Bellis, Claire, Bergman, Richard N, Blangero, John, Boban, Mladen, Boehnke, Michael, Boerwinkle, Eric, Bonnycastle, Lori L, Boomsma, Dorret I, Borecki, Ingrid B, Böttcher, Yvonne, Bouchard, Claude, Brunner, Eric, Budimir, Danijela, Campbell, Harry, Carlson, Olga, Chines, Peter S, Clarke, Robert, Collins, Francis S, Corbatón-Anchuelo, Arturo, Couper, David, de Faire, Ulf, Dedoussis, George V, Deloukas, Panos, Dimitriou, Maria, Egan, Josephine M, Eiriksdottir, Gudny, Erdos, Michael R, Eriksson, Johan G, Eury, Elodie, Ferrucci, Luigi, Ford, Ian, Forouhi, Nita G, Fox, Caroline S, Franzosi, Maria Grazia, Franks, Paul W, Frayling, Timothy M, Froguel, Philippe, Galan, Pilar, de Geus, Eco, Gigante, Bruna, Glazer, Nicole L, Goel, Anuj, Groop, Leif, Gudnason, Vilmundur, Hallmans, Göran, Hamsten, Anders, Hansson, Ola, Harris, Tamara B, Hayward, Caroline, Heath, Simon, Hercberg, Serge, Hicks, Andrew A, Hingorani, Aroon, Hofman, Albert, Hui, Jennie, Hung, Joseph, Jarvelin, Marjo-Riitta, Jhun, Min A, Johnson, Paul C D, Jukema, J Wouter, Jula, Antti, Kao, W H, Kaprio, Jaakko, Kardia, Sharon L R, Keinanen-Kiukaanniemi, Sirkka, Kivimaki, Mika, Kolcic, Ivana, Kovacs, Peter, Kumari, Meena, Kuusisto, Johanna, Kyvik, Kirsten Ohm, Laakso, Markku, Lakka, Timo, Lannfelt, Lars, Lathrop, G Mark, Launer, Lenore J, Leander, Karin, Li, Guo, Lind, Lars, Lindstrom, Jaana, Lobbens, Stéphane, Loos, Ruth J F, Luan, Jian'an, Lyssenko, Valeriya, Mägi, Reedik, Magnusson, Patrik K E, Marmot, Michael, Meneton, Pierre, Mohlke, Karen L, Mooser, Vincent, Morken, Mario A, Miljkovic, Iva, Narisu, Narisu, O'Connell, Jeff, Ong, Ken K, Oostra, Ben A, Palmer, Lyle J, Palotie, Aarno, Pankow, James S, Peden, John F, Pedersen, Nancy L, Pehlic, Marina, Peltonen, Leena, Penninx, Brenda, Pericic, Marijana, Perola, Markus, Perusse, Louis, Peyser, Patricia A, Polasek, Ozren, Pramstaller, Peter P, Province, Michael A, Räikkönen, Katri, Rauramaa, Rainer, Rehnberg, Emil, Rice, Ken, Rotter, Jerome I, Rudan, Igor, Ruokonen, Aimo, Saaristo, Timo, Sabater-Lleal, Maria, Salomaa, Veikko, Savage, David B, Saxena, Richa, Schwarz, Peter, Seedorf, Udo, Sennblad, Bengt, Serrano-Rios, Manuel, Shuldiner, Alan R, Sijbrands, Eric J G, Siscovick, David S, Smit, Johannes H, Small, Kerrin S, Smith, Nicholas L, Smith, Albert Vernon, Stančáková, Alena, Stirrups, Kathleen, Stumvoll, Michael, Sun, Yan V, Swift, Amy J, Tönjes, Anke, Tuomilehto, Jaakko, Trompet, Stella, Uitterlinden, Andre G, Uusitupa, Matti, Vikström, Max, Vitart, Veronique, Vohl, Marie-Claude, Voight, Benjamin F, Vollenweider, Peter, Waeber, Gerard, Waterworth, Dawn M, Watkins, Hugh, Wheeler, Eleanor, Widen, Elisabeth, Wild, Sarah H, Willems, Sara M, Willemsen, Gonneke, Wilson, James F, Witteman, Jacqueline C M, Wright, Alan F, Yaghootkar, Hanieh, Zelenika, Diana, Zemunik, Tatijana, Zgaga, Lina, Wareham, Nicholas J, McCarthy, Mark I, Barroso, Ines, Watanabe, Richard M, Florez, Jose C, Dupuis, Josée, Meigs, James B, and Langenberg, Claudia

Published
2012
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37. Cohort Profile: Epigenetics in Pregnancy (EPIPREG) – population-based sample of European and South Asian pregnant women living in Norway with epigenome-wide DNA methylation (850k) in peripheral blood leukocytes

Author

Fragoso-Bargas, Nicolas, primary, Opsahl, Julia O., additional, Kiryushchenko, Nadezhda, additional, Böttcher, Yvonne, additional, Lee-Ødegård, Sindre, additional, Qvigstad, Elisabeth, additional, Richardsen, Kåre Rønn, additional, Waage, Christin W., additional, Sletner, Line, additional, Jenum, Anne Karen, additional, Prasad, Rashmi B., additional, Groop, Leif C., additional, Moen, Gunn-Helen, additional, Birkeland, Kåre I., additional, and Sommer, Christine, additional

Published
2021
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39. Additional file 1 of DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial

Author

Keller, Maria, Meir, Anat Yaskolka, Bernhart, Stephan H., Yftach Gepner, Shelef, Ilan, Schwarzfuchs, Dan, Tsaban, Gal, Zelicha, Hila, Hopp, Lydia, Müller, Luise, Rohde, Kerstin, Böttcher, Yvonne, Stadler, Peter F., Stumvoll, Michael, Blüher, Matthias, Kovacs, Peter, and Shai, Iris

Abstract

Additional file 1. Detailed quality report of the Illumina EPIC 850 K raw data.

Published
2020
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45. Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans

Author

Ingelsson, Erik, Langenberg, Claudia, Hivert, Marie-France, Prokopenko, Inga, Lyssenko, Valeriya, Dupuis, Josée, Mägi, Reedik, Sharp, Stephen, Jackson, Anne U., Assimes, Themistocles L., Shrader, Peter, Knowles, Joshua W., Zethelius, Björn, Abbasi, Fahim A., Bergman, Richard N., Bergmann, Antje, Berne, Christian, Boehnke, Michael, Bonnycastle, Lori L., Bornstein, Stefan R., Buchanan, Thomas A., Bumpstead, Suzannah J., Böttcher, Yvonne, Chines, Peter, Collins, Francis S., Cooper, Cyrus C., Dennison, Elaine M., Erdos, Michael R., Ferrannini, Ele, Fox, Caroline S., Graessler, Jürgen, Hao, Ke, Isomaa, Bo, Jameson, Karen A., Kovacs, Peter, Kuusisto, Johanna, Laakso, Markku, Ladenvall, Claes, Mohlke, Karen L., Morken, Mario A., Narisu, Narisu, Nathan, David M., Pascoe, Laura, Payne, Felicity, Petrie, John R., Sayer, Avan A., Schwarz, Peter E., Scott, Laura J., Stringham, Heather M., Stumvoll, Michael, Swift, Amy J., Syvänen, Ann-Christine, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tönjes, Anke, Valle, Timo T., Williams, Gordon H., Lind, Lars, Barroso, Inês, Quertermous, Thomas, Walker, Mark, Wareham, Nicholas J., Meigs, James B., McCarthy, Mark I., Groop, Leif, Watanabe, Richard M., and Florez, Jose C.

Published
2010
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49. Common variants conferring risk of schizophrenia

Author

Stefansson, Hreinn, Ophoff, Roel A., Steinberg, Stacy, Andreassen, Ole A., Cichon, Sven, Rujescu, Dan, Werge, Thomas, Pietiläinen, Olli P. H., Mors, Ole, Mortensen, Preben B., Sigurdsson, Engilbert, Gustafsson, Omar, Nyegaard, Mette, Tuulio-Henriksson, Annamari, Ingason, Andres, Hansen, Thomas, Suvisaari, Jaana, Lonnqvist, Jouko, Paunio, Tiina, Børglum, Anders D., Hartmann, Annette, Fink-Jensen, Anders, Nordentoft, Merete, Hougaard, David, Norgaard-Pedersen, Bent, Böttcher, Yvonne, Olesen, Jes, Breuer, René, Möller, Hans-Jürgen, Giegling, Ina, Rasmussen, Henrik B., Timm, Sally, Mattheisen, Manuel, Bitter, István, Réthelyi, János M., Magnusdottir, Brynja B., Sigmundsson, Thordur, Olason, Pall, Masson, Gisli, Gulcher, Jeffrey R., Haraldsson, Magnus, Fossdal, Ragnheidur, Thorgeirsson, Thorgeir E., Thorsteinsdottir, Unnur, Ruggeri, Mirella, Tosato, Sarah, Franke, Barbara, Strengman, Eric, Kiemeney, Lambertus A., Kahn, René S., Linszen, Don H., van Os, Jim, Wiersma, Durk, Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Krabbendam, Lydia, Myin-Germeys, Inez, Melle, Ingrid, Djurovic, Srdjan, Abramova, Lilia, Kaleda, Vasily, Sanjuan, Julio, de Frutos, Rosa, Bramon, Elvira, Vassos, Evangelos, Fraser, Gillian, Ettinger, Ulrich, Picchioni, Marco, Walker, Nicholas, Toulopoulou, Timi, Need, Anna C., Ge, Dongliang, Lim Yoon, Joeng, Shianna, Kevin V., Freimer, Nelson B., Cantor, Rita M., Murray, Robin, Kong, Augustine, Golimbet, Vera, Carracedo, Angel, Arango, Celso, Costas, Javier, Jönsson, Erik G., Terenius, Lars, Agartz, Ingrid, Petursson, Hannes, Nöthen, Markus M., Rietschel, Marcella, Matthews, Paul M., Muglia, Pierandrea, Peltonen, Leena, St Clair, David, Goldstein, David B., Stefansson, Kari, and Collier, David A.

Published
2009
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