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2. Genetic variation of the ghrelin activator gene ghrelin O-acyltransferase ( GOAT) is associated with anorexia nervosa

Author

Müller, Timo D., Tschöp, Matthias H., Jarick, Ivonne, Ehrlich, Stefan, Scherag, Susann, Herpertz-Dahlmann, Beate, Zipfel, Stefan, Herzog, Wolfgang, de Zwaan, Martina, Burghardt, Roland, Fleischhaker, Christian, Klampfl, Karin, Wewetzer, Christoph, Herpertz, Stephan, Zeeck, Almut, Tagay, Sefik, Burgmer, Markus, Pfluger, Paul T., Scherag, André, Hebebrand, Johannes, and Hinney, Anke

Published
2011
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8. Fat Mass and Obesity-Associated Gene (FTO) in Eating Disorders: Evidence for Association of the rs9939609 Obesity Risk Allele with Bulimia nervosa and Anorexia nervosa

Author

Müller, Timo D., Greene, Brandon H., Bellodi, Laura, Cavallini, Maria C., Cellini, Elena, Di Bella, Daniela, Ehrlich, Stefan, Erzegovesi, Stefano, Estivill, Xavier, Fernández-Aranda, Fernando, Fichter, Manfred, Fleischhaker, Christian, Scherag, Susann, Gratacòs, Monica, Grallert, Harald, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Illig, Thomas, Lehmkuhl, Ulrike, Nacmias, Benedetta, Ribasés, Marta, Ricca, Valdo, Schäfer, Helmut, Scherag, André, Sorbi, Sandro, Wichmann, Heinz-Erich, Hebebrand, Johannes, and Hinney, Anke

Published
2012
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9. Genome-wide association study in German patients with attention deficit/hyperactivity disorder

Author

Hinney, Anke, Scherag, André, Jarick, Ivonne, Albayrak, Özgür, Pütter, Carolin, Pechlivanis, Sonali, Dauvermann, Maria R., Beck, Sebastian, Weber, Heike, Scherag, Susann, Nguyen, Trang T., Volckmar, Anna-Lena, Knoll, Nadja, Faraone, Stephen V., Neale, Benjamin M., Franke, Barbara, Cichon, Sven, Hoffmann, Per, Nöthen, Markus M., Schreiber, Stefan, Jöckel, Karl-Heinz, Wichmann, H.-Erich, Freitag, Christine, Lempp, Thomas, Meyer, Jobst, Gilsbach, Susanne, Herpertz-Dahlmann, Beate, Sinzig, Judith, Lehmkuhl, Gerd, Renner, Tobias J., Warnke, Andreas, Romanos, Marcel, Lesch, Klaus-Peter, Reif, Andreas, Schimmelmann, Benno G., and Hebebrand, Johannes

Published
2011
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15. Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity

Author

Rief Winfried, Scherag Susann, Vogel Carla IG, Grallert Harald, Scherag André, Greene Brandon H, Nguyen Trang T, Carrie Jophia, Wandolski Melanie, Brönner Günter, Müller Timo D, Wichmann Hans-Erich, Illig Thomas, Schäfer Helmut, Hebebrand Johannes, and Hinney Anke

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity. Methods We initially assessed association of five single nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the FAAH coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity. Results The trio analysis revealed some evidence for an association of three SNPs in FAAH (rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05). Conclusions As we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the FAAH variants analyzed here at least do not seem to play a major role in the etiology of obesity within our samples.

Published
2010
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16. Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS)

Author

Kimmig Rainer, Vogel Carla, Grallert Harald, Scherag Susann, Dietz Tiina, Lahner Harald, Hahn Susanne, Janssen Onno, Scherag André, Tan Susanne, Illig Thomas, Mann Klaus, Hebebrand Johannes, and Hinney Anke

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background The polycystic ovary syndrome (PCOS), a common endocrine disorder in women of child-bearing age, mainly characterised by chronic anovulation and hyperandrogenism, is often associated with insulin resistance (IR) and obesity. Its etiology and the role of IR and obesity in PCOS are not fully understood. We examined the influence of validated genetic variants conferring susceptibility to obesity and/or type 2 diabetes mellitus (T2DM) on metabolic and PCOS-specific traits in patients with PCOS. Methods We conducted an association study in 386 patients with PCOS (defined by the Rotterdam-criteria) using single nucleotide polymorphisms (SNPs) in or in proximity to the fat mass and obesity associated gene (FTO), insulin-induced gene-2 (INSIG2), transcription factor 7-like 2 gene (TCF7L2) and melanocortin 4 receptor gene (MC4R). To compare the effect of FTO obesity risk alleles on BMI in patients with PCOS to unselected females of the same age range we genotyped 1,971 females from the population-based KORA-S4 study (Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4). Results The FTO risk allele was associated with IR traits and measures of increased body weight. In addition, the TCF7L2 SNP was associated with body weight traits. For the SNPs in the vicinity of INSIG2 and MC4R and for the other examined phenotypes there was no evidence for an association. In PCOS the observed per risk allele effect of FTO intron 1 SNP rs9939609 on BMI was +1.56 kg/m2, whereas it was +0.46 kg/m2 in females of the same age range from the general population as shown previously. Conclusion The stronger effect on body weight of the FTO SNP in PCOS might well have implications for the etiology of the disease.

Published
2010
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17. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Author

Hinney, A., Kesselmeier, M., Huckins, Laura M, Hauser, Joanna, Karhunen, Leila, Meulenbelt, Ingrid, Slagboom, P Eline, Tortorella, Alfonso, Maj, Mario, Dedoussis, George, Dikeos, Dimitris, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Southam, Lorraine, Tsitsika, Artemis, Papezova, Hana, Slachtova, Lenka, Martaskova, Debora, Kennedy, James L, Levitan, Robert D, Yilmaz, Zeynep, Huemer, Julia, Koubek, Doris, Merl, Elisabeth, Rayner, N William, Wagner, Gudrun, Lichtenstein, Paul, Breen, Gerome, Cohen-Woods, Sarah, Farmer, Anne, McGuffin, Peter, Cichon, Sven, Giegling, Ina, Herms, Stefan, Rujescu, Dan, Tachmazidou, Ioanna, Schreiber, Stefan, Wichmann, H-Erich, Dina, Christian, Sladek, Rob, Gambaro, Giovanni, Soranzo, Nicole, Julia, Antonio, Marsal, Sara, Rabionet, Raquel, Gaborieau, Valerie, Klump, Kelly L, Dick, Danielle M, Palotie, Aarno, Ripatti, Samuli, Widén, Elisabeth, Andreassen, Ole A, Espeseth, Thomas, Lundervold, Astri, Reinvang, Ivar, Steen, Vidar M, Hellard, Stephanie Le, Treasure, Janet, Mattingsdal, Morten, Ntalla, Ioanna, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Navratilova, Marie, Gallinger, Steven, Pinto, Dalila, Scherer, Stephen W, Aschauer, Harald, Lewis, Cathryn M, Carlberg, Laura, Schosser, Alexandra, Alfredsson, Lars, Ding, Bo, Klareskog, Lars, Padyukov, Leonid, Finan, Chris, Kalsi, Gursharan, Roberts, Marion, Logan, Darren W, Schmidt, Ulrike, Peltonen, Leena, Ritchie, Graham R S, Barrett, Jeff C, Estivill, Xavier, Hinney, Anke, Sullivan, Patrick F, Collier, David A, Zeggini, Eleftheria, Bulik, Cynthia M, Anderson, Carl A, Tozzi, Federica, Barrett, Jeffrey C, Floyd, James A B, Franklin, Christopher S, McGinnis, Ralph, Sambrook, Jennifer, Stephens, Jonathan, Ouwehand, Willem H, McArdle, Wendy L, iezebrink, Kirsty, Ring, Susan M, Strachan, David P, Alexander, Graeme, Conlon, Peter J, Dominiczak, Anna, Duncanson, Audrey, Hill, Adrian, Langford, Cordelia, Jall, S., Hebebrand, Johannes, Lord, Graham, Maxwell, Alexander P, Morgan, Linda, Sandford, Richard N, Sheerin, Neil, Vannberg, Frederik O, Blackburn, Hannah, Chen, Wei-Min, Edkins, Sarah, Gorwood, Philip, Gillman, Mathew, Gray, Emma, Hunt, Sarah E, Nengut-Gumuscu, Suna, Potter, Simon, Rich, Stephen S, Simpkin, Douglas, Whittaker, Pamela, Heid, I. M., Winkler, T. W., Adan, Roger A H, de Bakker, P., Bültmann, U., Geleijnse, M., Harst, P. V., Koppelman, G., Rosmalen, J. G., van Rossum, L., Smidt, H., Swertz, M. A., Stolk, R. P., Kas, Martien J H, Alizadeh, B., de Boer, R., Boezen, H. M., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, H., van der Klauw, M., Navis, G., Ormel, J., Favaro, Angela, Postma, D., Rosmalen, J., Slaets, J., Snieder, H., Stolk, R., Wolffenbuttel, B., Wijmenga, C., Berg, J., Blackwood, D., Campbell, H., Santonastaso, Paolo, Cavanagh, J., Connell, J., Connor, M., Cunningham-Burley, S., Deary, I., Dominiczak, A., Ellis, P., FitzPatrick, B., Ford, I., Gertz, R., Fernández-Aranda, Fernando, Grau, A., Haddow, G., Jackson, C., Kerr, S., Lindsay, R., McGilchrist, M., McIntyre, D., Morris, A., Morton, R., Muir, W., Gratacos, Monica, Murray, G., Palmer, C., Pell, J., Philp, A., Porteous, D., Porteous, M., Procter, R., Ralston, S., Reid, D., Sinnott, R., Rybakowski, Filip, Smith, B., Clair, D. S., Sullivan, F., Sweetland, M., Ure, J., Watt, G., Wolf, R., Wright, A., Berndt, S. I., Gustafsson, S., Dmitrzak-Weglarz, Monika, Mägi, R., Ganna, A., Wheeler, E., Feitosa, M. F., Justice, A. E., Monda, K. L., Croteau- Chonka, D. C., Day, F. R., Esko, T., Fall, T., Volckmar, A-L, Kaprio, Jaakko, Ferreira, T., Gentilini, D., Jackson, A. U., Luan, J., Randall, J. C., Vedantam, S., Willer, C. J., Wood, A. R., Workalemahu, T., Keski-Rahkonen, Anna, Hu, Y. J., Lee, S. H., Liang, L., Lin, D. Y., Min, J. L., Neale, B. M., Thorleifsson, G., Yang, J., Albrecht, E., Amin, N., Raevuori-Helkamaa, Anu, Bragg-Gresham, J. L., Cadby, G., den Heijer, M., Eklund, N., Fischer, K., Goel, A., Hottenga, J. J., Huffman, J. E., Jarick, I., Johansson, A., Van Furth, Eric F, Johnson, T., Kanoni, S., Kleber, M. E., König, I. R., Kristiansson, K., Kutalik, Z., Lamina, C., Lecoeur, C., Li, G., Mangino, M., Slof-Op't Landt, Margarita C T, McArdle, W. L., Medina-Gomez, C., Müller-Nurasyid, M., Ngwa, J. S., Nolte, I. M., Paternoster, L., Pechlivanis, S., Perola, M., Peters, M. J., Preuss, M., Hudson, James I, Rose, L. M., Shi, J., Shungin, D., Smith, A. V., Strawbridge, R. J., Surakka, I., Teumer, A., Trip, M. D., Tyrer, J., Van Vliet- Ostaptchouk, J. V., Reichborn-Kjennerud, Ted, Vandenput, L., Waite, L. L., Zhao, J. H., Absher, D., Asselbergs, F. W., Atalay, M., Attwood, A. P., Balmforth, A. J., Basart, H., Beilby, J., Knudsen, Gun Peggy S, Bonnycastle, L. L., Brambilla, P., Chasman, D. I., Chines, P. S., Collins, F. S., Connell, J. M., Cookson, W., de Faire, U., Monteleone, Palmiero, de Vegt, F., Dei, M., Dimitriou, M., Edkins, S., Estrada, K., Evans, D. M., Farrall, M., Ferrario, M. M., Ferrières, J., Kaplan, Allan S, Frau, F., Gejman, P. V., Grallert, H., Grönberg, H., Gudnason, V., Hall, A. S., Hall, P., Hartikainen, A. L., Hayward, C., Heard-Costa, N. L., Föcker, M., Karwautz, Andreas, Heath, A. C., Hebebrand, J., Homuth, G., Hu, F. B., Hunt, S. E., Hyppönen, E., Iribarren, C., Jacobs, K. B., Jansson, J. O., Jula, A., Hakonarson, Hakon, Kähönen, M., Kathiresan, S., Kee, F., Khaw, K. T., Kivimaki, M., Koenig, W., Kraja, A. T., Kumari, M., Kuulasmaa, K., Kuusisto, J., Berrettini, Wade H, Laitinen, J. H., Lakka, T. A., Langenberg, C., Launer, L. J., Lind, L., Lindström, J., Liu, J., Liuzzi, A., Lokki, M. L., Lorentzon, M., Guo, Yiran, Madden, P. A., Magnusson, P. K., Manunta, P., Marek, D., März, W., Mateo Leach, I., McKnight, B., Medland, S. E., Mihailov, E., Milani, L., Li, Dong, Montgomery, G. W., Mooser, V., Mühleisen, T. W., Munroe, P. B., Musk, A. W., Narisu, N., Nicholson, G., Nohr, E. A., Ong, K. K., Schork, Nicholas J, Oostra, B. A., Palmer, C. N., Palotie, A., Peden, J. F., Pedersen, N., Peters, A., Polasek, O., Pouta, A., Pramstaller, P. P., Prokopenko, I., Komaki, Gen, Pütter, C., Radhakrishnan, A., Raitakari, O., Rendon, A., Rivadeneira, F., Rudan, I., Saaristo, T. E., Sambrook, J. G., Sanders, A. R., Sanna, S., Ando, Tetsuya, Saramies, J., Schipf, S., Schreiber, S., Schunkert, H., Shin, S. Y., Signorini, S., Sinisalo, J., Skrobek, B., Soranzo, N., Stancakova, A., Inoko, Hidetoshi, Stark, K., Stephens, J. C., Stirrups, K., Stumvoll, M., Swift, A. J., Theodoraki, E. V., Thorand, B., Tregouet, D. A., Tremoli, E., Esko, Tõnu, Van der Klauw, M. M., van Meurs, J. B., Vermeulen, S. H., Viikari, J., Virtamo, J., Vitart, V., Waeber, G., Wang, Z., Widen, E., Wild, S. H., Antel, J., Fischer, Krista, Willemsen, G., Winkelmann, B. R., Witteman, J. C., Wolffenbuttel, B. H., Wong, A., Wright, A. F., Zillikens, M., Amouyel, P., Boehm, B. O., Boerwinkle, E., Männik, Katrin, Boomsma, D. I., Caulfield, M. J., Chanock, S. J., Cupples, L., Cusi, D., Dedoussis, G. V., Erdmann, J., Eriksson, J. G., Franks, P. W., Froguel, P., Metspalu, Andres, Gieger, C., Gyllensten, U., Hamsten, A., Harris, T. B., Hengstenberg, C., Hicks, A. A., Hingorani, A., Hofman, A., Hovingh, K. G., Baker, Jessica H, Hveem, K., Illig, T., Jarvelin, M. R., Jöckel, K. H., Keinanen-Kiukaanniemi, S. M., Kiemeney, L. A., Kuh, D., Laakso, M., Lehtimäki, T., Levinson, D. F., Cone, Roger D, Martin, N. G., Metspalu, A., Morris, A. D., Nieminen, M. S., Njølstad, I., Ohlsson, C., Oldehinkel, A. J., Ouwehand, W. H., Palmer, L. J., Penninx, B., Dackor, Jennifer, Power, C., Province, M. A., Psaty, B. M., Qi, L., Rauramaa, R., Ridker, P. M., Ripatti, S., Salomaa, V., Samani, N. J., DeSocio, Janiece E, Sørensen, T. I., Spector, T. D., Stefansson, K., Tönjes, A., Tuomilehto, J., Uitterlinden, A. G., Uusitupa, M., Vollenweider, P., Wallaschofski, H., Hilliard, Christopher E, Wareham, N. J., Watkins, H., Wichmann, H, Wilson, J. F., Abecasis, G. R., Assimes, T. L., Barroso, I., Boehnke, M., Borecki, I. B., Deloukas, P., O'Toole, Julie K, Fox, C. S., Frayling, T., Groop, L. C., Haritunian, T., Hunter, D., Kaplan, R. C., Karpe, F., Moffatt, M., Mohlke, K. L., Pantel, Jacques, O'Connell, J. R., Pawitan, Y., Schadt, E. E., Schlessinger, D., Steinthorsdottir, V., Strachan, D. P., Thorsteinsdottir, U., van Duijn, C. M., Visscher, P. M., Di Blasio, A. M., Perica, Vesna Boraska, Szatkiewicz, Jin P, Hirschhorn, J. N., Lindgren, C. M., Morris, A. P., Meyre, D., Scherag, A., McCarthy, M. I., Speliotes, E. K., North, K. E., Loos, R. J., Grant, S. F. A., Taico, Chrysecolla, Adair, L. S., Ang, W., van Beijsterveldt, T., Bergen, N., Benke, K., Berry, D. J., Bradfield, J. P., Charoen, P., Zerwas, Stephanie, Coin, L., Cooper, C., Cousminer, D. L., Das, S., Davis, O. S., Elliott, P., Estivill, X., Feenstra, B., Trace, Sara E, Flexeder, C., Freathy, R. M., Gaillard, R., Geller, F., Gillman, M., Grant, S. F., Groen-Blokhuis, M., Goh, L. K., Guxens, M., Davis, Oliver S P, Hakonarson, H., Hattersley, A. T., Haworth, C. M., Hadley, D., Heinrich, J., Hocher, B., Holloway, J. W., Helder, Sietske, Holst, C., Horikoshi, M., Huikari, V., Hypponen, E., Iñiguez, C., Jaddoe, V. W., Kaakinen, M., Kilpeläinen, T. O., Bühren, Katharina, Kirin, M., Kowgier, M., Lakka, H. M., Lange, L. A., Lawlor, D. A., Lewin, A., Lindgren, C., Lindi, V., Burghardt, Roland, Maggi, R., Marsh, J., Melbye, M., Middeldorp, C., Millwood, I., Mook-Kanamori, D. O., Murray, J. C., Nivard, M., de Zwaan, Martina, Ntalla, I., Oken, E., O'Reilly, P. F., Panoutsopoulou, K., Pararajasingham, J., Pearson, E. R., Pennell, C. E., Egberts, Karin, Price, T. S., Raitakari, O. T., Rodriguez, A., Salem, R. M., Saw, S. M., Sebert, S., Siitonen, N., Ehrlich, Stefan, Simell, O., Sovio, U., Pourcain, B. S., Sunyer, J., Taal, H. R., Teo, Y. Y., Thiering, E., Tiesler, C., Herpertz-Dahlmann, Beate, Timpson, N. J., Valcárcel, B., Warrington, N. M., White, S., Widén, E., Yaghootkar, H., Zeggini, E., Herzog, Wolfgang, Elks, C. E., Perry, J. R., Sulem, P., Franceschini, N., He, C., Lunetta, K. L., Visser, J. A., Byrne, E. M., Imgart, Hartmut, Gudbjartsson, D. F., Koller, D. L., Lin, P., Marongiu, M., McArdle, P. F., Scherag, André, Stolk, L., van Wingerden, S. H., Corre, T., Ingelsson, E., Smith, E. N., Scherag, Susann, Ulivi, S., Warrington, M., Zgaga, L., Alavere, H., Aspelund, T., Bandinelli, S., Berenson, G. S., Bergmann, S., Zipfel, Stephan, Blackburn, H., Buring, J. E., Busonero, F., Chen, W., Cornelis, M. C., Couper, D., Coviello, A. D., Boni, Claudette, d'Adamo, P., de Geus, E. J., Döring, A., Davey Smith, G., Easton, D. F., Eiriksdottir, G., Emilsson, V., Eriksson, J., Ramoz, Nicolas, Ferrucci, L., Folsom, A. R., Foroud, T., Garcia, M., Gasparini, P., Hankinson, S. E., Versini, Audrey, Ferreli, L., Hernandez, D. G., Järvelin, M. R., Johnson, A. D., Karasik, D., Brandys, Marek K, Kiel, D. P., Kolcic, I., Kraft, P., Laven, J. S., Li, S., Levy, D., Danner, Unna N, Murray, S. S., Nalls, M. A., Navarro, P., Nelis, M., Ness, A. R., Northstone, K., de Kove, Carolien, Peacock, M., Paré, G., Parker, A. N., Pedersen, N. L., Peltonen, L., Pharoah, P., Hendriks, Judith, Plump, A. S., Porcu, E., Rafnar, T., Rice, J. P., Ring, S. M., Sala, C., Koeleman, Bobby P C, Schork, N. J., Scuteri, A., Segrè, A. V., Shuldiner, A. R., Srinivasan, S. R., Ophoff, Roel A, Tammesoo, M. L., Tikkanen, E., Toniolo, D., Tsui, K., Tryggvadottir, L., Uda, M., van Dam, R. M., Strengman, Eric, Waterworth, D. M., Weedon, M. N., Wichmann, H. E., Young, L., van Elburg, Annemarie A, Zhai, G., Zhuang, W. V., Bierut, L. J., Boyd, H. A., Crisponi, L., Demerath, E. W., Econs, M. J., Hunter, D. J., Bruson, Alice, Streeten, E. A., Clementi, Maurizio, Murabito, J. M., Murray, A., Guo, Y., Bergen, A. W., Kaye, W., Berrettini, W., Brandt, Harry, Crawford, Steve, Thornton, Laura M, Degortes, Daniela, Crow, Scott, Fichter, Manfred M, Halmi, Katherine A, Johnson, Craig, Via, Maria La, Mitchell, James, Strober, Michael, Rotondo, Alessandro, Forzan, Monica, Woodside, D Blake, Keel, Pamela, Lilenfeld, Lisa, Plotnicov, Kathy, Bergen, Andrew W, Berrettini, Wade, Kaye, Walter, Tenconi, Elena, Magistretti, Pierre, Herpertz-Dahlmann, B., de Zwaan, M., Herzog, W., Ehrlich, S., Zipfel, S., Egberts, K. M., Adan, R., Brandys, M., van Elburg, A., Docampo, Elisa, Boraska Perica, V., Franklin, C. S., Tschöp, M. H., Bulik, C. M., Collier, D., Müller, T. D., Escaramí, Geòrgia, Jiménez-Murcia, Susana, Lissowska, Jolanta, Rajewski, Andrzej, Szeszenia-Dabrowska, Neonila, Slopien, Agnieszka, Hinney, A., Kesselmeier, M., Jall, S., Volckmar, A. -L., Focker, M., Antel, J., Heid, I. M., Winkler, T. W., Grant, S. F. A., Guo, Y., Bergen, A. W., Kaye, W., Berrettini, W., Hakonarson, H., Herpertz-Dahlmann, B., De Zwaan, M., Herzog, W., Ehrlich, S., Zipfel, S., Egberts, K. M., Adan, R., Brandys, M., Van Elburg, A., Boraska Perica, V., Muller, T. D., Tschop, M. H., Zeggini, E., Bulik, C. M., Collier, D., Scherag, A., Hebebrand, J., Perica, V. B., Floyd, J. A. B., Thornton, L. M., Huckins, L. M., Southam, L., Rayner, N. W., Tachmazidou, I., Klump, K. L., Treasure, J., Lewis, C. M., Schmidt, U., Tozzi, F., Iezebrink, K., Gorwood, P., Kas, M. J. H., Favaro, A., Santonastaso, P., Fernandez-Aranda, F., Gratacos, M., Rybakowski, F., Dmitrzak-Weglarz, M., Kaprio, J., Keski-Rahkonen, A., Raevuori-Helkamaa, A., Van Furth, E. F., Slof-Op't Landt, M. C. T., Hudson, J. I., Reichborn-Kjennerud, T., Knudsen, G. P. S., Monteleone, P., Kaplan, A. S., Karwautz, A., Li, D., Komaki, G., Ando, T., Inoko, H., Esko, T., Fischer, K., Mannik, K., Metspalu, A., Baker, J. H., Cone, R. D., Dackor, J., Desocio, J. E., Hilliard, C. E., O'Toole, J. K., Pantel, J., Szatkiewicz, J. P., Taico, C., Zerwas, S., Trace, S. E., Davis, O. S. P., Helder, S., Buhren, K., Burghardt, R., Imgart, H., Scherag, S., Boni, C., Ramoz, N., Versini, A., Danner, U. N., de Kove, C., Hendriks, J., Koeleman, B. P. C., Ophoff, R. A., Strengman, E., Bruson, A., Clementi, M., Degortes, D., Forzan, M., Tenconi, E., Docampo, E., Jimenez-Murcia, G. E. S., Lissowska, J., Rajewski, A., Szeszenia-Dabrowska, N., Slopien, A., Hauser, J., Karhunen, L., Meulenbelt, I., Slagboom, P. E., Tortorella, A., Maj, M., Dedoussis, G., Dedoussis, G. V., Dikeos, D., Gonidakis, F., Tziouvas, K., Tsitsika, A., Papezova, H., Slachtova, L., Martaskova, D., Kennedy, J. L., Levitan, R. D., Yilmaz, Z., Huemer, J., Koubek, D., Merl, E., Wagner, G., Lichtenstein, P., Breen, G., Cohen-Woods, S., Farmer, A., Mcguffin, P., Cichon, S., Giegling, I., Herms, S., Rujescu, D., Schreiber, S., Wichmann, H. -E., Christian, D., Sladek, R., Gambaro, G., Soranzo, N., Julia, A., Marsal, S., Rabionet, R., Gaborieau, V., Dick, D. M., Palotie, A., Ripatti, S., Widen, E., Andreassen, O. A., Espeseth, T., Lundervold, A., Reinvang, I., Steen, V. M., Le Hellard, S., Mattingsdal, M., Ntalla, I., Bencko, V., Foretova, L., Janout, V., Navratilova, M., Gallinger, S., Pinto, D., Scherer, S. W., Aschauer, H., Carlberg, L., Schosser, A., Alfredsson, L., Ding, B., Klareskog, L., Padyukov, L., Finan, C., Kalsi, G., Roberts, M., Logan, D. W., Peltonen, L., Ritchie, G. R. S., Barrett, J. C., Estivill, X., Sullivan, P. F., Anderson, C. A., Mcginnis, R., Sambrook, J., Stephens, J., Ouwehand, W. H., Mcardle, W. L., Mcardle, P. F., Ring, S. M., Strachan, D. P., Alexander, G., Conlon, P. J., Dominiczak, A., Duncanson, A., Hill, A., Langford, C., Lord, G., Maxwell, A. P., Morgan, L., Sandford, R. N., Sheerin, N., Vannberg, F. O., Chen, W. -M., Edkins, S., Gillman, M., Gray, E., Hunt, S. E., Nengut, S. -G., Potter, S., Rich, S. S., Simpkin, D., Whittaker, P., Adair, L. S., Ang, W., Atalay, M., van Beijsterveldt, T., Bergen, N., Benke, K., Berry, D. J., Boomsma, D. I., Bradfield, J. P., Charoen, P., Coin, L., Cooper, C., Cousminer, D. L., Das, S., Elliott, P., Evans, D. M., Feenstra, B., Flexeder, C., Frayling, T., Freathy, R. M., Gaillard, R., Geller, F., Groen-Blokhuis, M., Goh, L. K., Guxens, M., Hattersley, A. T., Haworth, C. M., Hadley, D., Heinrich, J., Hirschhorn, J. N., Hocher, B., Holloway, J. W., Holst, C., Hottenga, J. J., Horikoshi, M., Huikari, V., Hypponen, E., Iniguez, C., Jaddoe, V. W., Jarvelin, M. R., Kaakinen, M., Kilpelainen, T. O., Kirin, M., Kowgier, M., Lakka, H. M., Lakka, T. A., Lange, L. A., Lawlor, D. A., Lehtimaki, T., Lewin, A., Lindgren, C., Lindi, V., Maggi, R., Marsh, J., Mccarthy, M. I., Melbye, M., Middeldorp, C., Millwood, I., Mohlke, K. L., Mook-Kanamori, D. O., Murray, J. C., Nivard, M., Nohr, E. A., Oken, E., Ong, K. K., O'Reilly, P. F., Palmer, L. J., Panoutsopoulou, K., Pararajasingham, J., Pearson, E. R., Pennell, C. E., Power, C., Price, T. S., Prokopenko, I., Raitakari, O. T., Rodriguez, A., Salem, R. M., Saw, S. M., Sebert, S., Siitonen, N., Simell, O., Sorensen, T. I., Sovio, U., Pourcain, B. S., Sunyer, J., Taal, H. R., Teo, Y. Y., Thiering, E., Tiesler, C., Timpson, N. J., Uitterlinden, A. G., Valcarcel, B., Warrington, N. M., White, S., Willemsen, G., Wilson, J. F., Yaghootkar, H., Elks, C. E., Perry, J. R., Sulem, P., Chasman, D. I., Franceschini, N., He, C., Lunetta, K. L., Visser, J. A., Byrne, E. M., Gudbjartsson, D. F., Koller, D. L., Kutalik, Z., Lin, P., Mangino, M., Marongiu, M., Smith, A. V., Stolk, L., van Wingerden, S. H., Zhao, J. H., Albrecht, E., Corre, T., Ingelsson, E., Hayward, C., Magnusson, P. K., Smith, E. N., Ulivi, S., Warrington, M., Zgaga, L., Alavere, H., Amin, N., Aspelund, T., Bandinelli, S., Barroso, I., Berenson, G. S., Bergmann, S., Boerwinkle, E., Buring, J. E., Busonero, F., Campbell, H., Chanock, S. J., Cornelis, M. C., Couper, D., Coviello, A. D., D'Adamo, P., de Faire, U., de Geus, E. J., Deloukas, P., Doring, A., Davey Smith, G., Easton, D. F., Eiriksdottir, G., Emilsson, V., Eriksson, J., Ferrucci, L., Folsom, A. R., Foroud, T., Garcia, M., Gasparini, P., Gieger, C., Gudnason, V., Hall, P., Hankinson, S. E., Ferreli, L., Heath, A. C., Hernandez, D. G., Hofman, A., Hu, F. B., Illig, T., Karasik, D., Khaw, K. T., Kiel, D. P., Kolcic, I., Kraft, P., Launer, L. J., Laven, J. S., Li, S., Liu, J., Levy, D., Martin, N. G., Mooser, V., Murray, S. S., Nalls, M. A., Navarro, P., Nelis, M., Ness, A. R., Northstone, K., Oostra, B. A., Peacock, M., Pare, G., Parker, A. N., Pedersen, N. L., Pharoah, P., Polasek, O., Plump, A. S., Pouta, A., Porcu, E., Rafnar, T., Rice, J. P., Rivadeneira, F., Rudan, I., Sala, C., Salomaa, V., Sanna, S., Schlessinger, D., Scuteri, A., Segre, A. V., Shuldiner, A. R., Srinivasan, S. R., Tammesoo, M. L., Tikkanen, E., Toniolo, D., Tsui, K., Tryggvadottir, L., Tyrer, J., Uda, M., van Dam, R. M., van Meurs, J. B., Vollenweider, P., Waeber, G., Wareham, N. J., Waterworth, D. M., Weedon, M. N., Wright, A. F., Young, L., Zhai, G., Zhuang, W. V., Bierut, L. J., Boyd, H. A., Crisponi, L., Demerath, E. W., van Duijn, C. M., Econs, M. J., Harris, T. B., Hunter, D. J., Loos, R. J., Ridker, P. M., Spector, T. D., Streeten, E. A., Stefansson, K., Thorsteinsdottir, U., Murabito, J. M., Murray, A., Brandt, H., Crawford, S., Crow, S., Fichter, M. M., Halmi, K. A., Johnson, C., La Via, M., Mitchell, J., Strober, M., Rotondo, A., Woodside, D. B., Keel, P., Lilenfeld, L., Plotnicov, K., Magistretti, P., Montgomery, G. W., Blackburn, H., Schork, N. J., Hinney, Anke, Kesselmeier, Miriam, Jall, Sigrid, Volckmar, Anna-Lena, Föcker, Manuel, Hebebrand, J, GCAN, WTCCC3, GIANT, EGG, Price Foundation Collaborative Group, Children’s Hospital of Philadelphia/Price Foundation, Cardiology, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ACS - Atherosclerosis & ischemic syndromes, Hinney, A, Kesselmeier, M, Jall, S, Volckmar, Al, Focker, M, Antel, J, Gcan, Wtccc3, Heid, Im, Winkler, Tw, Grant, Sfa, Giant, Manunta, P, Sfa, Grant, Egg, Guo, Y, Bergen, Aw, Kaye, W, Berrettini, W, Hakonarson, H, Price Foundation Collaborative, Group, Children’s Hospital of Philadelphia/Price, Foundation, Herpertz-Dahlmann, B, de Zwaan, M, Herzog, W, Ehrlich, S, Zipfel, S, Egberts, Km, Adan, R, Brandys, M, van Elburg, A, Perica, Vb, Franklin, C, Tschop, Mh, Zeggini, E, Bulik, Cm, Collier, D, Scherag, A, Muller, Td, Animal Ecology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, Volckmar, A-L, Föcker, M, Gcan, Wtccc, Gasparini, P, D'Adamo, A, Children’S Hospital of Philadelphia/Price, Foundation, Boraska Perica, V, Tschöp, Mh, and Müller, Td

Subjects
Netherlands Twin Register (NTR), Male, Anorexia Nervosa, Genome-wide association study, Cardiovascular, Linkage Disequilibrium, Body Mass Index, 0302 clinical medicine, Databases, Genetic, WTCCC3, Aetiology, Cancer, 0303 health sciences, Loci, Genetic Predisposition to Disease/genetics, Cross-disorder, Anorèxia nerviosa, anorexia nervosa (AN), Shared, 3. Good health, Psychiatry and Mental health, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Human, Alleles, Body Weight, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Obesity, Polymorphism, Single Nucleotide, Risk Factors, Molecular Biology, Psychiatry and Mental Health, Cellular and Molecular Neuroscience, medicine.medical_specialty, Locus (genetics), Single-nucleotide polymorphism, ta3111, Article, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, Genetics, EGG, Polymorphism, Children’s Hospital of Philadelphia/Price Foundation, body mass index (BMI), genome-wide association meta-analysis (GWAMA), Prevention, ta1184, medicine.disease, 030104 developmental biology, Endocrinology, diagnostic markers, Body mass index, Genètica, 030217 neurology & neurosurgery, 0301 basic medicine, Linkage disequilibrium, GIANT, Medizin, Obesity/genetics, Overweight, Medical and Health Sciences, Oral and gastrointestinal, Anorexia Nervosa/genetics, 2.1 Biological and endogenous factors, Psychiatry, 2. Zero hunger, Allele, Eating disorder, Single Nucleotide, Biological Sciences, Polymorphism, Single Nucleotide/genetics, Price Foundation Collaborative Group, Stroke, psychiatric disorders, Gene Frequency/genetics, medicine.symptom, Databases, Internal medicine, Body Weight/genetics, medicine, Journal Article, Linkage Disequilibrium/genetics, ddc:610, Metabolic and endocrine, Nutrition, 030304 developmental biology, GCAN, business.industry, Risk Factor, Human Genome, Psychology and Cognitive Sciences, Bulimia nervosa, business
Abstract

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values

Published
2017
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18. Genomweite Assoziationsstudien für Anorexia nervosa - warum finden wir so wenig? Symposium: 'Neue Erkenntnisse zu Genetik, Epigenetik und Neurobiologie bei Anorexia nervosa'

Author

Hinney, Anke, Scherag, André, Scherag, Susann, Bühren, Katharina, Herpertz-Dahlmann, Beate, Egberts, Karin, Burghardt, Roland, DeZwaan, Martina, Herzog, Wolfgang, Ehrlich, Stefan, Zipfel, Stephan, and Hebebrand, Johannes

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Genomweite Assoziationsstudien (GWAS) mittels Chip-basierter Analysen von Einzelbasenpaar-Austauschen (SNP) haben bislang zur Identifizierung von Genen für eine Vielzahl von komplexen Erkrankungen geführt. So wurden beispielsweise 32 genetische Loci beschrieben, die das Körpergewicht [for full text, please go to the a.m. URL], 3. Wissenschaftlicher Kongress der Deutschen Gesellschaft für Essstörungen

Published
2012
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19. Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder

Author

Jarick, Ivonne, Volckmar, Anna-Lena, Pütter, Carolin, Pechlivanis, Sonali, Nguyen, Trang T., Dauvermann, Maria R., Beck, Sebastian, Albayrak, Özgür, Scherag, Susann, Gilsbach, Susanne, Cichon, Sven, Hoffmann, Per, Degenhardt, Franziska, Nöthen, Markus Maria, Schreiber, Stefan, Wichmann, Heinz Erich, Jöckel, Karl-Heinz, Heinrich, Joachim, Tiesler, Carla Marie Thérèse, Faraone, Stephen V., Walitza, Susanne, Sinzig, Judith, Freitag, Christine M., Meyer, Jobst, Herpertz-Dahlmann, Beate, Lehmkuh, Gerd, Renner, Tobias J., Warnke, Andreas, Romanos, Marcel, Lesch, Klaus-Peter J., Reif, Andreas, Schimmelmann, Benno G., Hebebrand, Johannes, Scherag, André, Hinney, Anke, Jarick, Ivonne, Volckmar, Anna-Lena, Pütter, Carolin, Pechlivanis, Sonali, Nguyen, Trang T., Dauvermann, Maria R., Beck, Sebastian, Albayrak, Özgür, Scherag, Susann, Gilsbach, Susanne, Cichon, Sven, Hoffmann, Per, Degenhardt, Franziska, Nöthen, Markus Maria, Schreiber, Stefan, Wichmann, Heinz Erich, Jöckel, Karl-Heinz, Heinrich, Joachim, Tiesler, Carla Marie Thérèse, Faraone, Stephen V., Walitza, Susanne, Sinzig, Judith, Freitag, Christine M., Meyer, Jobst, Herpertz-Dahlmann, Beate, Lehmkuh, Gerd, Renner, Tobias J., Warnke, Andreas, Romanos, Marcel, Lesch, Klaus-Peter J., Reif, Andreas, Schimmelmann, Benno G., Hebebrand, Johannes, Scherag, André, and Hinney, Anke

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.

Published
2015

22. Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder

Author

Jarick, Ivonne, Volckmar, Anna-Lena, Pütter, Carolin, Pechlivanis, Sonali, Nguyen, Trang T, Dauvermann, Maria R, Beck, Sebastian, Albayrak, Özgür, Scherag, Susann, Gilsbach, Susanne, Cichon, Sven, Hoffmann, Per, Degenhardt, Franziska, Nöthen, Markus M, Schreiber, Stefan, Wichmann, H-Erich, Jöckel, Karl-Heinz, Heinrich, Joachim, Tiesler, Carla M T, Faraone, Stephen V, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Sinzig, Judith, Freitag, Christine, Meyer, Jobst, Herpertz-Dahlmann, Beate, Lehmkuhl, Gerd, Renner, Tobias J, Warnke, Andreas, Romanos, Marcel, Lesch, Klaus-Peter, Reif, Andreas, Schimmelmann, Benno G, Hebebrand, Johannes, Scherag, André, Hinney, Anke, Jarick, Ivonne, Volckmar, Anna-Lena, Pütter, Carolin, Pechlivanis, Sonali, Nguyen, Trang T, Dauvermann, Maria R, Beck, Sebastian, Albayrak, Özgür, Scherag, Susann, Gilsbach, Susanne, Cichon, Sven, Hoffmann, Per, Degenhardt, Franziska, Nöthen, Markus M, Schreiber, Stefan, Wichmann, H-Erich, Jöckel, Karl-Heinz, Heinrich, Joachim, Tiesler, Carla M T, Faraone, Stephen V, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Sinzig, Judith, Freitag, Christine, Meyer, Jobst, Herpertz-Dahlmann, Beate, Lehmkuhl, Gerd, Renner, Tobias J, Warnke, Andreas, Romanos, Marcel, Lesch, Klaus-Peter, Reif, Andreas, Schimmelmann, Benno G, Hebebrand, Johannes, Scherag, André, and Hinney, Anke

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency 1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.

Published
2014

23. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Author

Speliotes, Elizabeth K., Willer, Cristen J., Berndt, Sonja I., Monda, Keri L., Thorleifsson, Gudmar, Jackson, Anne U., Allen, Hana Lango, Lindgren, Cecilia M., Luan, Jian'an, Maegi, Reedik, Randall, Joshua C., Vedantam, Sailaja, Winkler, Thomas W., Qi, Lu, Workalemahu, Tsegaselassie, Heid, Iris M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Weedon, Michael N., Wheeler, Eleanor, Wood, Andrew R., Ferreira, Teresa, Weyant, Robert J., Segre, Ayellet V., Estrada, Karol, Liang, Liming, Nemesh, James, Park, Ju-Hyun, Gustafsson, Stefan, Kilpelaenen, Tuomas O., Yang, Jian, Bouatia-Naji, Nabila, Esko, Tonu, Feitosa, Mary F., Kutalik, Zoltan, Mangino, Massimo, Raychaudhuri, Soumya, Scherag, Andre, Smith, Albert Vernon, Welch, Ryan, Zhao, Jing Hua, Aben, Katja K., Absher, Devin M., Amin, Najaf, Dixon, Anna L., Fisher, Eva, Glazer, Nicole L., Goddard, Michael E., Heard-Costa, Nancy L., Hoesel, Volker, Hottenga, Jouke-Jan, Johansson, Åsa, Johnson, Toby, Ketkar, Shamika, Lamina, Claudia, Li, Shengxu, Moffatt, Miriam F., Myers, Richard H., Narisu, Narisu, Perry, John R. B., Peters, Marjolein J., Preuss, Michael, Ripatti, Samuli, Rivadeneira, Fernando, Sandholt, Camilla, Scott, Laura J., Timpson, Nicholas J., Tyrer, Jonathan P., van Wingerden, Sophie, Watanabe, Richard M., White, Charles C., Wiklund, Fredrik, Barlassina, Christina, Chasman, Daniel I., Cooper, Matthew N., Jansson, John-Olov, Lawrence, Robert W., Pellikka, Niina, Prokopenko, Inga, Shi, Jianxin, Thiering, Elisabeth, Alavere, Helene, Alibrandi, Maria T. S., Almgren, Peter, Arnold, Alice M., Aspelund, Thor, Atwood, Larry D., Balkau, Beverley, Balmforth, Anthony J., Bennett, Amanda J., Ben-Shlomo, Yoav, Bergman, Richard N., Bergmann, Sven, Biebermann, Heike, Blakemore, Alexandra I. F., Boes, Tanja, Bonnycastle, Lori L., Bornstein, Stefan R., Brown, Morris J., Buchanan, Thomas A., Busonero, Fabio, Campbell, Harry, Cappuccio, Francesco P., Cavalcanti-Proenca, Christine, Chen, Yii-Der Ida, Chen, Chih-Mei, Chines, Peter S., Clarke, Robert, Coin, Lachlan, Connell, John, Day, Ian N. M., den Heijer, Martin, Duan, Jubao, Ebrahim, Shah, Elliott, Paul, Elosua, Roberto, Eiriksdottir, Gudny, Erdos, Michael R., Eriksson, Johan G., Facheris, Maurizio F., Felix, Stephan B., Fischer-Posovszky, Pamela, Folsom, Aaron R., Friedrich, Nele, Freimer, Nelson B., Fu, Mao, Gaget, Stefan, Gejman, Pablo V., Geus, Eco J. C., Gieger, Christian, Gjesing, Anette P., Goel, Anuj, Goyette, Philippe, Grallert, Harald, Graessler, Juergen, Greenawalt, Danielle M., Groves, Christopher J., Gudnason, Vilmundur, Guiducci, Candace, Hartikainen, Anna-Liisa, Hassanali, Neelam, Hall, Alistair S., Havulinna, Aki S., Hayward, Caroline, Heath, Andrew C., Hengstenberg, Christian, Hicks, Andrew A., Hinney, Anke, Hofman, Albert, Homuth, Georg, Hui, Jennie, Igl, Wilmar, Iribarren, Carlos, Isomaa, Bo, Jacobs, Kevin B., Jarick, Ivonne, Jewell, Elizabeth, John, Ulrich, Jorgensen, Torben, Jousilahti, Pekka, Jula, Antti, Kaakinen, Marika, Kajantie, Eero, Kaplan, Lee M., Kathiresan, Sekar, Kettunen, Johannes, Kinnunen, Leena, Knowles, Joshua W., Kolcic, Ivana, Koenig, Inke R., Koskinen, Seppo, Kovacs, Peter, Kuusisto, Johanna, Kraft, Peter, Kvaloy, Kirsti, Laitinen, Jaana, Lantieri, Olivier, Lanzani, Chiara, Launer, Lenore J., Lecoeur, Cecile, Lehtimaeki, Terho, Lettre, Guillaume, Liu, Jianjun, Lokki, Marja-Liisa, Lorentzon, Mattias, Luben, Robert N., Ludwig, Barbara, Manunta, Paolo, Marek, Diana, Marre, Michel, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Anne, McKnight, Barbara, Meitinger, Thomas, Melander, Olle, Meyre, David, Midthjell, Kristian, Montgomery, Grant W., Morken, Mario A., Morris, Andrew P., Mulic, Rosanda, Ngwa, Julius S., Nelis, Mari, Neville, Matt J., Nyholt, Dale R., O'Donnell, Christopher J., O'Rahilly, Stephen, Ong, Ken K., Oostra, Ben, Pare, Guillaume, Parker, Alex N., Perola, Markus, Pichler, Irene, Pietilaeinen, Kirsi H., Platou, Carl G. P., Polasek, Ozren, Pouta, Anneli, Rafelt, Suzanne, Raitakari, Olli, Rayner, Nigel W., Ridderstrale, Martin, Rief, Winfried, Ruokonen, Aimo, Robertson, Neil R., Rzehak, Peter, Salomaa, Veikko, Sanders, Alan R., Sandhu, Manjinder S., Sanna, Serena, Saramies, Jouko, Savolainen, Markku J., Scherag, Susann, Schipf, Sabine, Schreiber, Stefan, Schunkert, Heribert, Silander, Kaisa, Sinisalo, Juha, Siscovick, David S., Smit, Jan H., Soranzo, Nicole, Sovio, Ulla, Stephens, Jonathan, Surakka, Ida, Swift, Amy J., Tammesoo, Mari-Liis, Tardif, Jean-Claude, Teder-Laving, Maris, Teslovich, Tanya M., Thompson, John R., Thomson, Brian, Toenjes, Anke, Tuomi, Tiinamaija, van Meurs, Joyce B. J., van Ommen, Gert-Jan, Vatin, Vincent, Viikari, Jorma, Visvikis-Siest, Sophie, Vitart, Veronique, Vogel, Carla I. G., Voight, Benjamin F., Waite, Lindsay L., Wallaschofski, Henri, Walters, G. Bragi, Widen, Elisabeth, Wiegand, Susanna, Wild, Sarah H., Willemsen, Gonneke, Witte, Daniel R., Witteman, Jacqueline C., Xu, Jianfeng, Zhang, Qunyuan, Zgaga, Lina, Ziegler, Andreas, Zitting, Paavo, Beilby, John P., Farooqi, I. Sadaf, Hebebrand, Johannes, Huikuri, Heikki V., James, Alan L., Kaehoenen, Mika, Levinson, Douglas F., Macciardi, Fabio, Nieminen, Markku S., Ohlsson, Claes, Palmer, Lyle J., Ridker, Paul M., Stumvoll, Michael, Beckmann, Jacques S., Boeing, Heiner, Boerwinkle, Eric, Boomsma, Dorret I., Caulfield, Mark J., Chanock, Stephen J., Collins, Francis S., Cupples, L. Adrienne, Smith, George Davey, Erdmann, Jeanette, Froguel, Philippe, Greonberg, Henrik, Gyllensten, Ulf, Hall, Per, Hansen, Torben, Harris, Tamara B., Hattersley, Andrew T., Hayes, Richard B., Heinrich, Joachim, Hu, Frank B., Hveem, Kristian, Illig, Thomas, Jarvelin, Marjo-Riitta, Kaprio, Jaakko, Karpe, Fredrik, Khaw, Kay-Tee, Kiemeney, Lambertus A., Krude, Heiko, Laakso, Markku, Lawlor, Debbie A., Metspalu, Andres, Munroe, Patricia B., Ouwehand, Willem H., Pedersen, Oluf, Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Quertermous, Thomas, Reinehr, Thomas, Rissanen, Aila, Rudan, Igor, Samani, Nilesh J., Schwarz, Peter E. H., Shuldiner, Alan R., Spector, Timothy D., Tuomilehto, Jaakko, Uda, Manuela, Uitterlinden, Andre, Valle, Timo T., Wabitsch, Martin, Waeber, Gerard, Wareham, Nicholas J., Watkins, Hugh, Wilson, James F., Wright, Alan F., Zillikens, M. Carola, Chatterjee, Nilanjan, McCarroll, Steven A., Purcell, Shaun, Schadt, Eric E., Visscher, Peter M., Assimes, Themistocles L., Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Haritunians, Talin, Hunter, David J., Kaplan, Robert C., Mohlke, Karen L., O'Connell, Jeffrey R., Peltonen, Leena, Schlessinger, David, Strachan, David P., van Duijn, Cornelia M., Wichmann, H-Erich, Frayling, Timothy M., Thorsteinsdottir, Unnur, Abecasis, Goncalo R., Barroso, Ines, Boehnke, Michael, Stefansson, Kari, North, Kari E., McCarthy, Mark I., Hirschhorn, Joel N., Ingelsson, Erik, Loos, Ruth J. F., Speliotes, Elizabeth K., Willer, Cristen J., Berndt, Sonja I., Monda, Keri L., Thorleifsson, Gudmar, Jackson, Anne U., Allen, Hana Lango, Lindgren, Cecilia M., Luan, Jian'an, Maegi, Reedik, Randall, Joshua C., Vedantam, Sailaja, Winkler, Thomas W., Qi, Lu, Workalemahu, Tsegaselassie, Heid, Iris M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Weedon, Michael N., Wheeler, Eleanor, Wood, Andrew R., Ferreira, Teresa, Weyant, Robert J., Segre, Ayellet V., Estrada, Karol, Liang, Liming, Nemesh, James, Park, Ju-Hyun, Gustafsson, Stefan, Kilpelaenen, Tuomas O., Yang, Jian, Bouatia-Naji, Nabila, Esko, Tonu, Feitosa, Mary F., Kutalik, Zoltan, Mangino, Massimo, Raychaudhuri, Soumya, Scherag, Andre, Smith, Albert Vernon, Welch, Ryan, Zhao, Jing Hua, Aben, Katja K., Absher, Devin M., Amin, Najaf, Dixon, Anna L., Fisher, Eva, Glazer, Nicole L., Goddard, Michael E., Heard-Costa, Nancy L., Hoesel, Volker, Hottenga, Jouke-Jan, Johansson, Åsa, Johnson, Toby, Ketkar, Shamika, Lamina, Claudia, Li, Shengxu, Moffatt, Miriam F., Myers, Richard H., Narisu, Narisu, Perry, John R. B., Peters, Marjolein J., Preuss, Michael, Ripatti, Samuli, Rivadeneira, Fernando, Sandholt, Camilla, Scott, Laura J., Timpson, Nicholas J., Tyrer, Jonathan P., van Wingerden, Sophie, Watanabe, Richard M., White, Charles C., Wiklund, Fredrik, Barlassina, Christina, Chasman, Daniel I., Cooper, Matthew N., Jansson, John-Olov, Lawrence, Robert W., Pellikka, Niina, Prokopenko, Inga, Shi, Jianxin, Thiering, Elisabeth, Alavere, Helene, Alibrandi, Maria T. S., Almgren, Peter, Arnold, Alice M., Aspelund, Thor, Atwood, Larry D., Balkau, Beverley, Balmforth, Anthony J., Bennett, Amanda J., Ben-Shlomo, Yoav, Bergman, Richard N., Bergmann, Sven, Biebermann, Heike, Blakemore, Alexandra I. F., Boes, Tanja, Bonnycastle, Lori L., Bornstein, Stefan R., Brown, Morris J., Buchanan, Thomas A., Busonero, Fabio, Campbell, Harry, Cappuccio, Francesco P., Cavalcanti-Proenca, Christine, Chen, Yii-Der Ida, Chen, Chih-Mei, Chines, Peter S., Clarke, Robert, Coin, Lachlan, Connell, John, Day, Ian N. M., den Heijer, Martin, Duan, Jubao, Ebrahim, Shah, Elliott, Paul, Elosua, Roberto, Eiriksdottir, Gudny, Erdos, Michael R., Eriksson, Johan G., Facheris, Maurizio F., Felix, Stephan B., Fischer-Posovszky, Pamela, Folsom, Aaron R., Friedrich, Nele, Freimer, Nelson B., Fu, Mao, Gaget, Stefan, Gejman, Pablo V., Geus, Eco J. C., Gieger, Christian, Gjesing, Anette P., Goel, Anuj, Goyette, Philippe, Grallert, Harald, Graessler, Juergen, Greenawalt, Danielle M., Groves, Christopher J., Gudnason, Vilmundur, Guiducci, Candace, Hartikainen, Anna-Liisa, Hassanali, Neelam, Hall, Alistair S., Havulinna, Aki S., Hayward, Caroline, Heath, Andrew C., Hengstenberg, Christian, Hicks, Andrew A., Hinney, Anke, Hofman, Albert, Homuth, Georg, Hui, Jennie, Igl, Wilmar, Iribarren, Carlos, Isomaa, Bo, Jacobs, Kevin B., Jarick, Ivonne, Jewell, Elizabeth, John, Ulrich, Jorgensen, Torben, Jousilahti, Pekka, Jula, Antti, Kaakinen, Marika, Kajantie, Eero, Kaplan, Lee M., Kathiresan, Sekar, Kettunen, Johannes, Kinnunen, Leena, Knowles, Joshua W., Kolcic, Ivana, Koenig, Inke R., Koskinen, Seppo, Kovacs, Peter, Kuusisto, Johanna, Kraft, Peter, Kvaloy, Kirsti, Laitinen, Jaana, Lantieri, Olivier, Lanzani, Chiara, Launer, Lenore J., Lecoeur, Cecile, Lehtimaeki, Terho, Lettre, Guillaume, Liu, Jianjun, Lokki, Marja-Liisa, Lorentzon, Mattias, Luben, Robert N., Ludwig, Barbara, Manunta, Paolo, Marek, Diana, Marre, Michel, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Anne, McKnight, Barbara, Meitinger, Thomas, Melander, Olle, Meyre, David, Midthjell, Kristian, Montgomery, Grant W., Morken, Mario A., Morris, Andrew P., Mulic, Rosanda, Ngwa, Julius S., Nelis, Mari, Neville, Matt J., Nyholt, Dale R., O'Donnell, Christopher J., O'Rahilly, Stephen, Ong, Ken K., Oostra, Ben, Pare, Guillaume, Parker, Alex N., Perola, Markus, Pichler, Irene, Pietilaeinen, Kirsi H., Platou, Carl G. P., Polasek, Ozren, Pouta, Anneli, Rafelt, Suzanne, Raitakari, Olli, Rayner, Nigel W., Ridderstrale, Martin, Rief, Winfried, Ruokonen, Aimo, Robertson, Neil R., Rzehak, Peter, Salomaa, Veikko, Sanders, Alan R., Sandhu, Manjinder S., Sanna, Serena, Saramies, Jouko, Savolainen, Markku J., Scherag, Susann, Schipf, Sabine, Schreiber, Stefan, Schunkert, Heribert, Silander, Kaisa, Sinisalo, Juha, Siscovick, David S., Smit, Jan H., Soranzo, Nicole, Sovio, Ulla, Stephens, Jonathan, Surakka, Ida, Swift, Amy J., Tammesoo, Mari-Liis, Tardif, Jean-Claude, Teder-Laving, Maris, Teslovich, Tanya M., Thompson, John R., Thomson, Brian, Toenjes, Anke, Tuomi, Tiinamaija, van Meurs, Joyce B. J., van Ommen, Gert-Jan, Vatin, Vincent, Viikari, Jorma, Visvikis-Siest, Sophie, Vitart, Veronique, Vogel, Carla I. G., Voight, Benjamin F., Waite, Lindsay L., Wallaschofski, Henri, Walters, G. Bragi, Widen, Elisabeth, Wiegand, Susanna, Wild, Sarah H., Willemsen, Gonneke, Witte, Daniel R., Witteman, Jacqueline C., Xu, Jianfeng, Zhang, Qunyuan, Zgaga, Lina, Ziegler, Andreas, Zitting, Paavo, Beilby, John P., Farooqi, I. Sadaf, Hebebrand, Johannes, Huikuri, Heikki V., James, Alan L., Kaehoenen, Mika, Levinson, Douglas F., Macciardi, Fabio, Nieminen, Markku S., Ohlsson, Claes, Palmer, Lyle J., Ridker, Paul M., Stumvoll, Michael, Beckmann, Jacques S., Boeing, Heiner, Boerwinkle, Eric, Boomsma, Dorret I., Caulfield, Mark J., Chanock, Stephen J., Collins, Francis S., Cupples, L. Adrienne, Smith, George Davey, Erdmann, Jeanette, Froguel, Philippe, Greonberg, Henrik, Gyllensten, Ulf, Hall, Per, Hansen, Torben, Harris, Tamara B., Hattersley, Andrew T., Hayes, Richard B., Heinrich, Joachim, Hu, Frank B., Hveem, Kristian, Illig, Thomas, Jarvelin, Marjo-Riitta, Kaprio, Jaakko, Karpe, Fredrik, Khaw, Kay-Tee, Kiemeney, Lambertus A., Krude, Heiko, Laakso, Markku, Lawlor, Debbie A., Metspalu, Andres, Munroe, Patricia B., Ouwehand, Willem H., Pedersen, Oluf, Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Quertermous, Thomas, Reinehr, Thomas, Rissanen, Aila, Rudan, Igor, Samani, Nilesh J., Schwarz, Peter E. H., Shuldiner, Alan R., Spector, Timothy D., Tuomilehto, Jaakko, Uda, Manuela, Uitterlinden, Andre, Valle, Timo T., Wabitsch, Martin, Waeber, Gerard, Wareham, Nicholas J., Watkins, Hugh, Wilson, James F., Wright, Alan F., Zillikens, M. Carola, Chatterjee, Nilanjan, McCarroll, Steven A., Purcell, Shaun, Schadt, Eric E., Visscher, Peter M., Assimes, Themistocles L., Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Groop, Leif C., Haritunians, Talin, Hunter, David J., Kaplan, Robert C., Mohlke, Karen L., O'Connell, Jeffrey R., Peltonen, Leena, Schlessinger, David, Strachan, David P., van Duijn, Cornelia M., Wichmann, H-Erich, Frayling, Timothy M., Thorsteinsdottir, Unnur, Abecasis, Goncalo R., Barroso, Ines, Boehnke, Michael, Stefansson, Kari, North, Kari E., McCarthy, Mark I., Hirschhorn, Joel N., Ingelsson, Erik, and Loos, Ruth J. F.

Abstract

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation., De sju sista författarna delar sistaförfattarskapet.

Published
2010
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24. Addendum: Genome‐wide association study in German patients with attention deficit/hyperactivity disorder

Author

Hinney, Anke, primary, Scherag, André, additional, Jarick, Ivonne, additional, Albayrak, Özgür, additional, Pütter, Carolin, additional, Pechlivanis, Sonali, additional, Dauvermann, Maria R., additional, Beck, Sebastian, additional, Weber, Heike, additional, Scherag, Susann, additional, Nguyen, Trang T., additional, Volckmar, Anna‐Lena, additional, Knoll, Nadja, additional, Faraone, Stephen V., additional, Neale, Benjamin M., additional, Franke, Barbara, additional, Cichon, Sven, additional, Hoffmann, Per, additional, Nöthen, Markus M., additional, Schreiber, Stefan, additional, Jöckel, Karl‐Heinz, additional, Wichmann, H.‐Erich, additional, Freitag, Christine, additional, Lempp, Thomas, additional, Meyer, Jobst, additional, Gilsbach, Susanne, additional, Herpertz‐Dahlmann, Beate, additional, Sinzig, Judith, additional, Lehmkuhl, Gerd, additional, Renner, Tobias J., additional, Warnke, Andreas, additional, Romanos, Marcel, additional, Lesch, Klaus‐Peter, additional, Reif, Andreas, additional, Schimmelmann, Benno G., additional, and Hebebrand, Johannes, additional

Published
2012
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26. Do Common Variants Separate between Obese Melanocortin-4 Receptor Gene Mutation Carriers and Non-Carriers? The Impact of Cryptic Relatedness

Author

Mühlhaus, Jessica, primary, Pütter, Carolin, additional, Brumm, Harald, additional, Grallert, Harald, additional, Illig, Thomas, additional, Scherag, Susann, additional, Reinehr, Thomas, additional, Pott, Wilfried, additional, Albayrak, Özgür, additional, Wang, Hai-Jun, additional, Bau, Anne-Madeleine, additional, Wiegand, Susanna, additional, Grüters, Annette, additional, Krude, Heiko, additional, Hebebrand, Johannes, additional, Hinney, Anke, additional, Biebermann, Heike, additional, and Scherag, André, additional

Published
2012
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28. Investigation of a Genome Wide Association Signal for Obesity: Synthetic Association and Haplotype Analyses at the Melanocortin 4 Receptor Gene Locus

Author

Scherag, André, primary, Jarick, Ivonne, additional, Grothe, Jessica, additional, Biebermann, Heike, additional, Scherag, Susann, additional, Volckmar, Anna-Lena, additional, Vogel, Carla Ivane Ganz, additional, Greene, Brandon, additional, Hebebrand, Johannes, additional, and Hinney, Anke, additional

Published
2010
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29. Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

Author

Scherag, André, primary, Dina, Christian, additional, Hinney, Anke, additional, Vatin, Vincent, additional, Scherag, Susann, additional, Vogel, Carla I. G., additional, Müller, Timo D., additional, Grallert, Harald, additional, Wichmann, H.-Erich, additional, Balkau, Beverley, additional, Heude, Barbara, additional, Jarvelin, Marjo-Riitta, additional, Hartikainen, Anna-Liisa, additional, Levy-Marchal, Claire, additional, Weill, Jacques, additional, Delplanque, Jérôme, additional, Körner, Antje, additional, Kiess, Wieland, additional, Kovacs, Peter, additional, Rayner, Nigel W., additional, Prokopenko, Inga, additional, McCarthy, Mark I., additional, Schäfer, Helmut, additional, Jarick, Ivonne, additional, Boeing, Heiner, additional, Fisher, Eva, additional, Reinehr, Thomas, additional, Heinrich, Joachim, additional, Rzehak, Peter, additional, Berdel, Dietrich, additional, Borte, Michael, additional, Biebermann, Heike, additional, Krude, Heiko, additional, Rosskopf, Dieter, additional, Rimmbach, Christian, additional, Rief, Winfried, additional, Fromme, Tobias, additional, Klingenspor, Martin, additional, Schürmann, Annette, additional, Schulz, Nadja, additional, Nöthen, Markus M., additional, Mühleisen, Thomas W., additional, Erbel, Raimund, additional, Jöckel, Karl-Heinz, additional, Moebus, Susanne, additional, Boes, Tanja, additional, Illig, Thomas, additional, Froguel, Philippe, additional, Hebebrand, Johannes, additional, and Meyre, David, additional

Published
2010
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31. Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS)

Author

Tan, Susanne, primary, Scherag, André, additional, Janssen, Onno Eilard, additional, Hahn, Susanne, additional, Lahner, Harald, additional, Dietz, Tiina, additional, Scherag, Susann, additional, Grallert, Harald, additional, Vogel, Carla Ivane Ganz, additional, Kimmig, Rainer, additional, Illig, Thomas, additional, Mann, Klaus, additional, Hebebrand, Johannes, additional, and Hinney, Anke, additional

Published
2010
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32. Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity

Author

Müller, Timo D, primary, Brönner, Günter, additional, Wandolski, Melanie, additional, Carrie, Jophia, additional, Nguyen, Trang T, additional, Greene, Brandon H, additional, Scherag, André, additional, Grallert, Harald, additional, Vogel, Carla IG, additional, Scherag, Susann, additional, Rief, Winfried, additional, Wichmann, Hans-Erich, additional, Illig, Thomas, additional, Schäfer, Helmut, additional, Hebebrand, Johannes, additional, and Hinney, Anke, additional

Published
2010
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34. The 5-HTTLPR polymorphism, platelet serotonin transporter activity and platelet serotonin content in underweight and weight-recovered females with anorexia nervosa

Author

Ehrlich, Stefan, primary, Franke, Leonora, additional, Scherag, Susann, additional, Burghardt, Roland, additional, Schott, Regina, additional, Schneider, Nora, additional, Brockhaus, Simone, additional, Hein, Jakob, additional, Uebelhack, Ralf, additional, and Lehmkuhl, Ulrike, additional

Published
2009
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35. Large effects on body mass index and insulin resistance of fat mass and obesity associated gene variants in patients with polycystic (FTO) ovary syndrome (PCOS).

Author

Tan, Susanne, Scherag, André, Janssen, Onno Eilard, Hahn, Susanne, Lahner, Harald, Dietz, Tiina, Scherag, Susann, Grallert, Harald, Vogel, Carla Ivane Ganz, Kimmig, Rainer, Illig, Thomas, Mann, Klaus, Hebebrand, Johannes, and Hinney, Anke

Subjects
OBESITY in women, BODY mass index, INSULIN resistance, ETIOLOGY of diseases, POLYCYSTIC ovary syndrome
Abstract

Background: The polycystic ovary syndrome (PCOS), a common endocrine disorder in women of child-bearing age, mainly characterised by chronic anovulation and hyperandrogenism, is often associated with insulin resistance (IR) and obesity. Its etiology and the role of IR and obesity in PCOS are not fully understood. We examined the influence of validated genetic variants conferring susceptibility to obesity and/or type 2 diabetes mellitus (T2DM) on metabolic and PCOS-specific traits in patients with PCOS. Methods: We conducted an association study in 386 patients with PCOS (defined by the Rotterdam-criteria) using single nucleotide polymorphisms (SNPs) in or in proximity to the fat mass and obesity associated gene (FTO), insulin-induced gene-2 (INSIG2), transcription factor 7-like 2 gene (TCF7L2) and melanocortin 4 receptor gene (MC4R). To compare the effect of FTO obesity risk alleles on BMI in patients with PCOS to unselected females of the same age range we genotyped 1,971 females from the population-based KORA-S4 study (Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4). Results: The FTO risk allele was associated with IR traits and measures of increased body weight. In addition, the TCF7L2 SNP was associated with body weight traits. For the SNPs in the vicinity of INSIG2 and MC4R and for the other examined phenotypes there was no evidence for an association. In PCOS the observed per risk allele effect of FTO intron 1 SNP rs9939609 on BMI was +1.56 kg/m², whereas it was +0.46 kg/m² in females of the same age range from the general population as shown previously. Conclusion: The stronger effect on body weight of the FTO SNP in PCOS might well have implications for the etiology of the disease. [ABSTRACT FROM AUTHOR]

Published
2010
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36. A genome-wide association study of anorexia nervosa

Author

Boraska, Vesna, Franklin, Christopher S, Floyd, James AB, Thornton, Laura M, Huckins, Laura M, Southam, Lorraine, Rayner, N William, Tachmazidou, Ioanna, Klump, Kelly L, Treasure, Janet, Lewis, Cathryn M, Schmidt, Ulrike, Tozzi, Federica, Kiezebrink, Kirsty, Hebebrand, Johannes, Gorwood, Philip, Adan, Roger AH, Kas, Martien JH, Favaro, Angela, Santonastaso, Paolo, Fernández-Aranda, Fernando, Gratacos, Monica, Rybakowski, Filip, Dmitrzak-Weglarz, Monika, Kaprio, Jaakko, Keski-Rahkonen, Anna, Raevuori, Anu, Van Furth, Eric F, Slof-Op t Landt, Margarita CT, Hudson, James I, Reichborn-Kjennerud, Ted, Knudsen, Gun Peggy S, Monteleone, Palmiero, Kaplan, Allan S, Karwautz, Andreas, Hakonarson, Hakon, Berrettini, Wade H, Guo, Yiran, Li, Dong, Schork, Nicholas J., Komaki, Gen, Ando, Tetsuya, Inoko, Hidetoshi, Esko, Tõnu, Fischer, Krista, Männik, Katrin, Metspalu, Andres, Baker, Jessica H, Cone, Roger D, Dackor, Jennifer, DeSocio, Janiece E, Hilliard, Christopher E, O’Toole, Julie K, Pantel, Jacques, Szatkiewicz, Jin P, Taico, Chrysecolla, Zerwas, Stephanie, Trace, Sara E, Davis, Oliver SP, Helder, Sietske, Bühren, Katharina, Burghardt, Roland, de Zwaan, Martina, Egberts, Karin, Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Imgart, Hartmut, Scherag, André, Scherag, Susann, Zipfel, Stephan, Boni, Claudette, Ramoz, Nicolas, Versini, Audrey, Brandys, Marek K, Danner, Unna N, de Kovel, Carolien, Hendriks, Judith, Koeleman, Bobby PC, Ophoff, Roel A, Strengman, Eric, van Elburg, Annemarie A, Bruson, Alice, Clementi, Maurizio, Degortes, Daniela, Forzan, Monica, Tenconi, Elena, Docampo, Elisa, Escaramís, Geòrgia, Jiménez-Murcia, Susana, Lissowska, Jolanta, Rajewski, Andrzej, Szeszenia-Dabrowska, Neonila, Slopien, Agnieszka, Hauser, Joanna, Karhunen, Leila, Meulenbelt, Ingrid, Slagboom, P Eline, Tortorella, Alfonso, Maj, Mario, Dedoussis, George, Dikeos, Dimitris, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Tsitsika, Artemis, Papezova, Hana, Slachtova, Lenka, Martaskova, Debora, Kennedy, James L., Levitan, Robert D., Yilmaz, Zeynep, Huemer, Julia, Koubek, Doris, Merl, Elisabeth, Wagner, Gudrun, Lichtenstein, Paul, Breen, Gerome, Cohen-Woods, Sarah, Farmer, Anne, McGuffin, Peter, Cichon, Sven, Giegling, Ina, Herms, Stefan, Rujescu, Dan, Schreiber, Stefan, Wichmann, H-Erich, Dina, Christian, Sladek, Rob, Gambaro, Giovanni, Soranzo, Nicole, Julia, Antonio, Marsal, Sara, Rabionet, Raquel, Gaborieau, Valerie, Dick, Danielle M, Palotie, Aarno, Ripatti, Samuli, Widén, Elisabeth, Andreassen, Ole A, Espeseth, Thomas, Lundervold, Astri, Reinvang, Ivar, Steen, Vidar M, Le Hellard, Stephanie, Mattingsdal, Morten, Ntalla, Ioanna, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Navratilova, Marie, Gallinger, Steven, Pinto, Dalila, Scherer, Stephen, Aschauer, Harald, Carlberg, Laura, Schosser, Alexandra, Alfredsson, Lars, Ding, Bo, Klareskog, Lars, Padyukov, Leonid, Finan, Chris, Kalsi, Gursharan, Roberts, Marion, Logan, Darren W, Peltonen, Leena, Ritchie, Graham RS, Barrett, Jeffrey C, Estivill, Xavier, Hinney, Anke, Sullivan, Patrick F, Collier, David A, Zeggini, Eleftheria, and Bulik, Cynthia M

Subjects
anorexia nervosa, eating disorders, GWAS, genome-wide association study, body mass index, metabolic
Abstract

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10−7) in SOX2OT and rs17030795 (P=5.84×10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10−6) between CUL3 and FAM124B and rs1886797 (P=8.05×10−6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4×10−6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Published
2013
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37. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts

Author

Benjamin Voight, Guillaume Pare, Ruth Loos, Michael Preuss, Åsa Johansson, Eco De Geus, Michael Weedon, Marjo-Riitta Jarvelin, Joyce Van Meurs, Torben Jørgensen, Kirsi Pietiläinen, Nicole Glazer, Mattias Lorentzon, Braxton Mitchell, Nicole Soranzo, Patricia Munroe, Ozren Polasek, Elisabeth Thiering, Marika Kaakinen, Carla Vogel, Jennie Hui, Elina Hypponen, ROBERTO ELOSUA, Amanda Bennett, Michael Stumvoll, Andrew Hattersley, Peter P Pramstaller, Lambertus Kiemeney, Sophie Visvikis-Siest, Vilmundur Gudnason, John Whittaker, Aroon Hingorani, Thor Aspelund, Dale Nyholt, Mary Feitosa, Vimal Karani, Mika Kähönen, Lachlan Coin, Malcolm Dunlop, Josee Dupuis, Terho Lehtimäki, Peter Visscher, Katja Aben, Daniel Witte, Cyrus Cooper, Stefan Pilz, Willem Ouwehand, Eleanor Wheeler, Peter Kovacs, Debbie A Lawlor, Kevin Jacobs, Evropi Theodoratou, Hana Lango Allen, Rosanda Mulic, Rui Li, Stephen Kritchevsky, Philippe Froguel, Soumya Raychaudhuri, Cornelia Van Duijn, Andrew Wood, Chiara Lanzani, Tonu Esko, Sadaf Farooqi, Reedik Mägi, Gerard Waeber, Claes Ohlsson, André Scherag, Marcus Kleber, Thomas Meitinger, Lina Zgaga, Denise Houston, Karl Michaëlsson, Robert Weyant, Thomas Wang, Paul Elliott, Robert Luben, Albert Vernon Smith, MANUELA UDA, Gonneke Willemsen, Mark McCarthy, Cecilia Lindgren, Olle Melander, Igor Rudan, Maris Teder-Laving, Liesbeth Vandenput, Vimaleswaran, K, Berry, Dj, Lu, C, Tikkanen, E, Pilz, S, Hiraki, Lt, Cooper, Jd, Dastani, Z, Li, R, Houston, Dk, Wood, Ar, Michaëlsson, K, Vandenput, L, Zgaga, L, YERGES ARMSTRONG, Lm, Mccarthy, Mi, Dupuis, J, Kaakinen, M, Kleber, Me, Jameson, K, Arden, N, Raitakari, O, Viikari, J, Lohman, Kk, Ferrucci, L, Melhus, H, Ingelsson, E, Byberg, L, Lind, L, Lorentzon, M, Salomaa, V, Campbell, H, Dunlop, M, Mitchell, Bd, Herzig, Kh, Pouta, A, Hartikainen, Al, Manunta, Paolo, Streeten, Ea, Theodoratou, E, Jula, A, Wareham, Nj, Ohlsson, C, Frayling, Tm, Kritchevsky, Sb, Spector, Td, Richards, Jb, Lehtimäki, T, Ouwehand, Wh, Kraft, P, Cooper, C, März, W, Power, C, Loos, Rj, Wang, Tj, Järvelin, Mr, Whittaker, Jc, Hingorani, Ad, Hyppönen, E., Council, Medical Research, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Institute for Molecular Medicine Finland, Haartman Institute (-2014), Transplantation Laboratory, Vimaleswaran, Karani S, Berry, Diane J, Lu, Chen, Tikkanen, Emmi, Hyppönen, Elina, Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Hinney, Anke (Beitragende*r), Scherag, Susann (Beitragende*r), Hebebrand, Johannes (Beitragende*r), Epidemiology and Data Science, Psychiatry, EMGO - Lifestyle, overweight and diabetes, Genetic Investigation of Anthropometric Traits-GIANT Consortium, Speliotes, E.K., Willer, C.J., Berndt, S.I., Monda, K.L., Thorleifsson, G., Jackson, A.U., Allen, H.L., Lindgren, C.M., Jian'an, L., Mägi, R., Randall, J.C., Vedantam, S., Winkler, T.W., Qi, L., Workalemahu, T., Heid, I.M., Steinthorsdottir, V., Stringham, H.M., Weedon, M.N., Wheeler, E., Wood, A.R., Ferreira, T., Weyant, R.J., Segrè, A.V., Estrada, K., Liang, L., Nemesh, J., Park, J.H., Gustafsson, S., Kilpeläinen, T.O., Yang, J., Bouatia-Naji, N., Tõnu, E., Feitosa, M.F., Kutalik, Z., Mangino, M., Raychaudhuri, S., Scherag, A., Smith, A.V., Welch, R., Zhao, J.H., Aben, K.K., Absher, D.M., Amin, N., Dixon, A.L., Fisher, E., Glazer, N.L., Goddard, M.E., Heard-Costa, N.L., Hoesel, V., Hottenga, J.J., Johansson, Å., Johnson, T., Ketkar, S., Lamina, C., Li, S., Moffatt, M.F., Myers, R.H., Narisu, N., Perry, J.R., Peters, M.J., Preuss, M., Ripatti, S., Rivadeneira, F., Sandholt, C., Scott, L.J., Timpson, N.J., Tyrer, J.P., van Wingerden, S., Watanabe, R.M., White, C.C., Wiklund, F., Barlassina, C., Chasman, D.I., Cooper, M.N., Jansson, J.O., Lawrence, R.W., Pellikka, N., Prokopenko, I., Shi, J., Thiering, E., Alavere, H., Alibrandi, M.T., Almgren, P., Arnold, A.M., Aspelund, T., Atwood, L.D., Balkau, B., Balmforth, A.J., Bennett, A.J., Ben-Shlomo, Y., Bergman, R.N., Bergmann, S., Biebermann, H., Blakemore, A.I., Boes, T., Bonnycastle, L.L., Bornstein, S.R., Brown, M.J., Buchanan, T.A., Busonero, F., Campbell, H., Cappuccio, F.P., Cavalcanti-Proença, C., Chen, Y.D., Chen, C.M., Chines, P.S., Clarke, R., Coin, L., Connell, J., Day, I.N., Heijer, M., Duan, J., Ebrahim, S., Elliott, P., Elosua, R., Eiriksdottir, G., Erdos, M.R., Eriksson, J.G., Facheris, M.F., Felix, S.B., Fischer-Posovszky, P., Folsom, A.R., Friedrich, N., Freimer, N.B., Fu, M., Gaget, S., Gejman, P.V., Geus, E.J., Gieger, C., Gjesing, A.P., Goel, A., Goyette, P., Grallert, H., Gräßler, J., Greenawalt, D.M., Groves, C.J., Gudnason, V., Guiducci, C., Hartikainen, A.L., Hassanali, N., Hall, A.S., Havulinna, A.S., Hayward, C., Heath, A.C., Hengstenberg, C., Hicks, A.A., Hinney, A., Hofman, A., Homuth, G., Hui, J., Igl, W., Iribarren, C., Isomaa, B., Jacobs, K.B., Jarick, I., Jewell, E., John, U., Jørgensen, T., Jousilahti, P., Jula, A., Kaakinen, M., Kajantie, E., Kaplan, L.M., Kathiresan, S., Kettunen, J., Kinnunen, L., Knowles, J.W., Kolcic, I., König, I.R., Koskinen, S., Kovacs, P., Kuusisto, J., Kraft, P., Kvaløy, K., Laitinen, J., Lantieri, O., Lanzani, C., Launer, L.J., Lecoeur, C., Lehtimäki, T., Lettre, G., Liu, J., Lokki, M.L., Lorentzon, M., Luben, R.N., Ludwig, B., Manunta, P., Marek, D., Marre, M., Martin, N.G., McArdle, W.L., McCarthy, A., McKnight, B., Meitinger, T., Melander, O., Meyre, D., Midthjell, K., Montgomery, G.W., Morken, M.A., Morris, A.P., Mulic, R., Ngwa, J.S., Nelis, M., Neville, M.J., Nyholt, D.R., O'Donnell, C.J., O'Rahilly, S., Ong, K.K., Oostra, B., Paré, G., Parker, A.N., Perola, M., Pichler, I., Pietiläinen, K.H., Platou, C.G., Polasek, O., Pouta, A., Rafelt, S., Raitakari, O., Rayner, N.W., Ridderstråle, M., Rief, W., Ruokonen, A., Robertson, N.R., Rzehak, P., Salomaa, V., Sanders, A.R., Sandhu, M.S., Sanna, S., Saramies, J., Savolainen, M.J., Scherag, S., Schipf, S., Schreiber, S., Schunkert, H., Silander, K., Sinisalo, J., Siscovick, D.S., Smit, J.H., Soranzo, N., Sovio, U., Stephens, J., Surakka, I., Swift, AJ., Tammesoo, M.L., Tardif, J.C., Teder-Laving, M., Teslovich, T.M., Thompson, J.R., Thomson, B., Tönjes, A., Tuomi, T., van Meurs, J.B., van Ommen, G.J., Vatin, V., Viikari, J., Visvikis-Siest, S., Vitart, V., Vogel, C.I., Voight, B.F., Waite, L.L., Wallaschofski, H., Walters, G.B., Widen, E., Wiegand, S., Wild, S.H., Willemsen, G., Witte, D.R., Witteman, J.C., Xu, J., Zhang, Q., Zgaga, L., Ziegler, A., Zitting, P., Beilby, J.P., Farooqi, I.S., Hebebrand, J., Huikuri, H.V., James, AL., Kähönen, M., Levinson, D.F., Macciardi, F., Nieminen, M.S., Ohlsson, C., Palmer, L.J., Ridker, P.M., Stumvoll, M., Beckmann, J.S., Boeing, H., Boerwinkle, E., Boomsma, D.I., Caulfield, M.J., Chanock, S.J., Collins, F.S., Cupples, L.A., Smith, G.D., Erdmann, J., Froguel, P., Grönberg, H., Gyllensten, U., Hall, P., Hansen, T., Harris, T.B., Hattersley, A.T., Hayes, R.B., Heinrich, J., Hu, F.B., Hveem, K., Illig, T., Jarvelin, M.R., Kaprio, J., Karpe, F., Khaw, K.T., Kiemeney, L.A., Krude, H., Laakso, M., Lawlor, D.A., Metspalu, A., Munroe, P.B., Ouwehand, W.H., Pedersen, O., Penninx, B.W., Peters, A., Pramstaller, P.P., Quertermous, T., Reinehr, T., Rissanen, A., Rudan, I., Samani, N.J., Schwarz, P.E., Shuldiner, A.R., Spector, T.D., Tuomilehto, J., Uda, M., Uitterlinden, A., Valle, T.T., Wabitsch, M., Waeber, G., Wareham, N.J., Watkins, H., Wilson, J.F., Wright, A.F., Zillikens, M.C., Chatterjee, N., McCarroll, S.A., Purcell, S., Schadt, E.E., Visscher, P.M., Assimes, T.L., Borecki, I.B., Deloukas, P., Fox, C.S., Groop, L.C., Haritunians, T., Hunter, D.J., Kaplan, R.C., Mohlke, K.L., O'Connell, J.R., Peltonen, L., Schlessinger, D., Strachan, D.P., van Duijn, C.M., Wichmann, H.E., Frayling, T.M., Thorsteinsdottir, U., Abecasis, G.R., Barroso, I., Boehnke, M., Stefansson, K., North, K.E., McCarthy, M.I., Hirschhorn, J.N., Ingelsson, E., Loos, R.J., Medical Research Council (MRC), and National Institute for Health Research

Subjects
Male, Netherlands Twin Register (NTR), Medicin och hälsovetenskap, obesity, 25-HYDROXYVITAMIN D, D INSUFFICIENCY, Epidemiology, Medizin, vitamin D, Aetiology, screening and detection [ONCOL 5], Medical and Health Sciences, Gastroenterology, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, GENETIC-VARIANTS, Medicine, 030212 general & internal medicine, Vitamin D, 2. Zero hunger, Genetics, Aged, 80 and over, Evidence-Based Medicine, Confounding, 11 Medical And Health Sciences, General Medicine, Middle Aged, 3. Good health, PREVALENCE, Europe, Phenotype, Genetic Epidemiology, Biological Markers, Female, Life Sciences & Biomedicine, Research Article, Vitamin, Adult, medicine.medical_specialty, vitamin D deficiency, genetic variants, Genetic Investigation of Anthropometric Traits-GIANT Consortium, European Continental Ancestry Group, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, body mass index, Polymorphism, Single Nucleotide, Risk Assessment, White People, COMMON OBESITY, 03 medical and health sciences, D DEFICIENCY, Medicine, General & Internal, SDG 3 - Good Health and Well-being, General & Internal Medicine, Internal medicine, Mendelian randomization, Vitamin D and neurology, INSTRUMENTAL VARIABLES, Humans, Genetic Predisposition to Disease, Obesity, GENOME-WIDE ASSOCIATION, Biology, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], Aged, Science & Technology, Population Biology, business.industry, CARDIOVASCULAR-DISEASE RISK, ta3121, Mendelian Randomization Analysis, medicine.disease, Vitamin D Deficiency, BODY-MASS INDEX, chemistry, Genetic epidemiology, 3121 General medicine, internal medicine and other clinical medicine, Multivariate Analysis, North America, Genetic Polymorphism, Linear Models, business, Body mass index, Population Genetics, Biomarkers
Abstract

A mendelian randomization study based on data from multiple cohorts conducted by Karani Santhanakrishnan Vimaleswaran and colleagues re-examines the causal nature of the relationship between vitamin D levels and obesity., Background Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m2 higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10−27). The BMI allele score was associated both with BMI (p = 6.30×10−62) and 25(OH)D (−0.06% [95% CI −0.10 to −0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10−57 for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: −4.2 [95% CI −7.1 to −1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). Conclusions On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency. Please see later in the article for the Editors' Summary, Editors' Summary Background Obesity—having an unhealthy amount of body fat—is increasing worldwide. In the US, for example, a third of the adult population is now obese. Obesity is defined as having a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of more than 30.0 kg/m2. Although there is a genetic contribution to obesity, people generally become obese by consuming food and drink that contains more energy than they need for their daily activities. Thus, obesity can be prevented by having a healthy diet and exercising regularly. Compared to people with a healthy weight, obese individuals have an increased risk of developing diabetes, heart disease and stroke, and tend to die younger. They also have a higher risk of vitamin D deficiency, another increasingly common public health concern. Vitamin D, which is essential for healthy bones as well as other functions, is made in the skin after exposure to sunlight but can also be obtained through the diet and through supplements. Why Was This Study Done? Observational studies cannot prove that obesity causes vitamin D deficiency because obese individuals may share other characteristics that reduce their circulating 25-hydroxy vitamin D [25(OH)D] levels (referred to as confounding). Moreover, observational studies cannot indicate whether the larger vitamin D storage capacity of obese individuals (vitamin D is stored in fatty tissues) lowers their 25(OH)D levels or whether 25(OH)D levels influence fat accumulation (reverse causation). If obesity causes vitamin D deficiency, monitoring and treating vitamin D deficiency might alleviate some of the adverse health effects of obesity. Conversely, if low vitamin D levels cause obesity, encouraging people to take vitamin D supplements might help to control the obesity epidemic. Here, the researchers use bi-directional “Mendelian randomization” to examine the direction and causality of the relationship between BMI and 25(OH)D. In Mendelian randomization, causality is inferred from associations between genetic variants that mimic the influence of a modifiable environmental exposure and the outcome of interest. Because gene variants do not change over time and are inherited randomly, they are not prone to confounding and are free from reverse causation. Thus, if a lower vitamin D status leads to obesity, genetic variants associated with lower 25(OH)D concentrations should be associated with higher BMI, and if obesity leads to a lower vitamin D status, then genetic variants associated with higher BMI should be associated with lower 25(OH)D concentrations. What Did the Researchers Do and Find? The researchers created a “BMI allele score” based on 12 BMI-related gene variants and two “25(OH)D allele scores,” which are based on gene variants that affect either 25(OH)D synthesis or breakdown. Using information on up to 42,024 participants from 21 studies, the researchers showed that the BMI allele score was associated with both BMI and with 25(OH)D levels among the study participants. Based on this information, they calculated that each 10% increase in BMI will lead to a 4.2% decrease in 25(OH)D concentrations. By contrast, although both 25(OH)D allele scores were strongly associated with 25(OH)D levels, neither score was associated with BMI. This lack of an association between 25(OH)D allele scores and obesity was confirmed using data from more than 100,000 individuals involved in 46 studies that has been collected by the GIANT (Genetic Investigation of Anthropometric Traits) consortium. What Do These Findings Mean? These findings suggest that a higher BMI leads to a lower vitamin D status whereas any effects of low vitamin D status on BMI are likely to be small. That is, these findings provide evidence for obesity as a causal factor in the development of vitamin D deficiency but not for vitamin D deficiency as a causal factor in the development of obesity. These findings suggest that population-level interventions to reduce obesity should lead to a reduction in the prevalence of vitamin D deficiency and highlight the importance of monitoring and treating vitamin D deficiency as a means of alleviating the adverse influences of obesity on health. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001383. The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (in English and Spanish); a data brief provides information about the vitamin D status of the US population The World Health Organization provides information on obesity (in several languages) The UK National Health Service Choices website provides detailed information about obesity and a link to a personal story about losing weight; it also provides information about vitamin D The International Obesity Taskforce provides information about the global obesity epidemic The US Department of Agriculture's ChooseMyPlate.gov website provides a personal healthy eating plan; the Weight-control Information Network is an information service provided for the general public and health professionals by the US National Institute of Diabetes and Digestive and Kidney Diseases (in English and Spanish) The US Office of Dietary Supplements provides information about vitamin D (in English and Spanish) MedlinePlus has links to further information about obesity and about vitamin D (in English and Spanish) Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) Overview and details of the collaborative large-scale genetic association study (D-CarDia) provide information about vitamin D and the risk of cardiovascular disease, diabetes and related traits

Published
2013
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38. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

Author

Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Lango Allen H, Lindgren CM, Luan J, Mägi R, Randall JC, Vedantam S, Winkler TW, Qi L, Workalemahu T, Heid IM, Steinthorsdottir V, Stringham HM, Weedon MN, Wheeler E, Wood AR, Ferreira T, Weyant RJ, Segrè AV, Estrada K, Liang L, Nemesh J, Park JH, Gustafsson S, Kilpeläinen TO, Yang J, Bouatia-Naji N, Esko T, Feitosa MF, Kutalik Z, Mangino M, Raychaudhuri S, Scherag A, Smith AV, Welch R, Zhao JH, Aben KK, Absher DM, Amin N, Dixon AL, Fisher E, Glazer NL, Goddard ME, Heard-Costa NL, Hoesel V, Hottenga JJ, Johansson A, Johnson T, Ketkar S, Lamina C, Li S, Moffatt MF, Myers RH, Narisu N, Perry JR, Peters MJ, Preuss M, Ripatti S, Rivadeneira F, Sandholt C, Scott LJ, Timpson NJ, Tyrer JP, van Wingerden S, Watanabe RM, White CC, Wiklund F, Barlassina C, Chasman DI, Cooper MN, Jansson JO, Lawrence RW, Pellikka N, Prokopenko I, Shi J, Thiering E, Alavere H, Alibrandi MT, Almgren P, Arnold AM, Aspelund T, Atwood LD, Balkau B, Balmforth AJ, Bennett AJ, Ben-Shlomo Y, Bergman RN, Bergmann S, Biebermann H, Blakemore AI, Boes T, Bonnycastle LL, Bornstein SR, Brown MJ, Buchanan TA, Busonero F, Campbell H, Cappuccio FP, Cavalcanti-Proença C, Chen YD, Chen CM, Chines PS, Clarke R, Coin L, Connell J, Day IN, den Heijer M, Duan J, Ebrahim S, Elliott P, Elosua R, Eiriksdottir G, Erdos MR, Eriksson JG, Facheris MF, Felix SB, Fischer-Posovszky P, Folsom AR, Friedrich N, Freimer NB, Fu M, Gaget S, Gejman PV, Geus EJ, Gieger C, Gjesing AP, Goel A, Goyette P, Grallert H, Grässler J, Greenawalt DM, Groves CJ, Gudnason V, Guiducci C, Hartikainen AL, Hassanali N, Hall AS, Havulinna AS, Hayward C, Heath AC, Hengstenberg C, Hicks AA, Hinney A, Hofman A, Homuth G, Hui J, Igl W, Iribarren C, Isomaa B, Jacobs KB, Jarick I, Jewell E, John U, Jørgensen T, Jousilahti P, Jula A, Kaakinen M, Kajantie E, Kaplan LM, Kathiresan S, Kettunen J, Kinnunen L, Knowles JW, Kolcic I, König IR, Koskinen S, Kovacs P, Kuusisto J, Kraft P, Kvaløy K, Laitinen J, Lantieri O, Lanzani C, Launer LJ, Lecoeur C, Lehtimäki T, Lettre G, Liu J, Lokki ML, Lorentzon M, Luben RN, Ludwig B, Manunta P, Marek D, Marre M, Martin NG, McArdle WL, McCarthy A, McKnight B, Meitinger T, Melander O, Meyre D, Midthjell K, Montgomery GW, Morken MA, Morris AP, Mulic R, Ngwa JS, Nelis M, Neville MJ, Nyholt DR, O'Donnell CJ, O'Rahilly S, Ong KK, Oostra B, Paré G, Parker AN, Perola M, Pichler I, Pietiläinen KH, Platou CG, Polasek O, Pouta A, Rafelt S, Raitakari O, Rayner NW, Ridderstråle M, Rief W, Ruokonen A, Robertson NR, Rzehak P, Salomaa V, Sanders AR, Sandhu MS, Sanna S, Saramies J, Savolainen MJ, Scherag S, Schipf S, Schreiber S, Schunkert H, Silander K, Sinisalo J, Siscovick DS, Smit JH, Soranzo N, Sovio U, Stephens J, Surakka I, Swift AJ, Tammesoo ML, Tardif JC, Teder-Laving M, Teslovich TM, Thompson JR, Thomson B, Tönjes A, Tuomi T, van Meurs JB, van Ommen GJ, Vatin V, Viikari J, Visvikis-Siest S, Vitart V, Vogel CI, Voight BF, Waite LL, Wallaschofski H, Walters GB, Widen E, Wiegand S, Wild SH, Willemsen G, Witte DR, Witteman JC, Xu J, Zhang Q, Zgaga L, Ziegler A, Zitting P, Beilby JP, Farooqi IS, Hebebrand J, Huikuri HV, James AL, Kähönen M, Levinson DF, Macciardi F, Nieminen MS, Ohlsson C, Palmer LJ, Ridker PM, Stumvoll M, Beckmann JS, Boeing H, Boerwinkle E, Boomsma DI, Caulfield MJ, Chanock SJ, Collins FS, Cupples LA, Smith GD, Erdmann J, Froguel P, Grönberg H, Gyllensten U, Hall P, Hansen T, Harris TB, Hattersley AT, Hayes RB, Heinrich J, Hu FB, Hveem K, Illig T, Jarvelin MR, Kaprio J, Karpe F, Khaw KT, Kiemeney LA, Krude H, Laakso M, Lawlor DA, Metspalu A, Munroe PB, Ouwehand WH, Pedersen O, Penninx BW, Peters A, Pramstaller PP, Quertermous T, Reinehr T, Rissanen A, Rudan I, Samani NJ, Schwarz PE, Shuldiner AR, Spector TD, Tuomilehto J, Uda M, Uitterlinden A, Valle TT, Wabitsch M, Waeber G, Wareham NJ, Watkins H, Wilson JF, Wright AF, Zillikens MC, Chatterjee N, McCarroll SA, Purcell S, Schadt EE, Visscher PM, Assimes TL, Borecki IB, Deloukas P, Fox CS, Groop LC, Haritunians T, Hunter DJ, Kaplan RC, Mohlke KL, O'Connell JR, Peltonen L, Schlessinger D, Strachan DP, van Duijn CM, Wichmann HE, Frayling TM, Thorsteinsdottir U, Abecasis GR, Barroso I, Boehnke M, Stefansson K, North KE, McCarthy MI, Hirschhorn JN, Ingelsson E, and Loos RJ

Subjects
Body Size genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Humans, Obesity genetics, Polymorphism, Single Nucleotide, White People genetics, Body Height genetics, Body Mass Index, Body Weight genetics, Chromosome Mapping
Abstract

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Published
2010
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39. Genetic findings in anorexia and bulimia nervosa.

Author

Hinney A, Scherag S, and Hebebrand J

Subjects
Environment, Genome-Wide Association Study, Humans, Twin Studies as Topic, Anorexia genetics, Bulimia Nervosa genetics
Abstract

Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders associated with disordered eating behavior. Heritability estimates derived from twin and family studies are high, so that substantial genetic influences on the etiology can be assumed for both. As the monoaminergic neurotransmitter systems are involved in eating disorders (EDs), candidate gene studies have centered on related genes; additionally, genes relevant for body weight regulation have been considered as candidates. Unfortunately, this approach has yielded very few positive results; confirmed associations or findings substantiated in meta-analyses are scant. None of these associations can be considered unequivocally validated. Systematic genome-wide approaches have been performed to identify genes with no a priori evidence for their relevance in EDs. Family-based scans revealed linkage peaks in single chromosomal regions for AN and BN. Analyses of candidate genes in one of these regions led to the identification of genetic variants associated with AN. Currently, an international consortium is conducting a genome-wide association study for AN, which will hopefully lead to the identification of the first genome-wide significant markers., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Published
2010
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