40 results on '"Jarick, I."'
Search Results
2. Lack of synthetic association for the melanocortin 4 receptor gene in obesity: V 14
- Author
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Scherag, A., Jarick, I., Grothe, J., Biebermann, H., Scherag, S., Volckmar, A.-L., Vogel, C. I.G., Greene, B., Hebebrand, J., and Hinney, A.
- Published
- 2012
3. A NOVEL RARE NON-SYNONYMOUS, NON-CONSERVATIVE MUTATION IN THE SH2B1 GENE IN OVERWEIGHT AND OBESE INDIVIDUALS: 636 accepted poster
- Author
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Volckmar, A. L., Jarick, I., Knoll, N., Scherag, A., Reinehr, T., Illig, T., Grallert, H., Wichmann, H. E., Biebermann, H., Krude, H., Fischer-Posovszky, P., Rief, W., Bolze, F., Klingenspor, M., Wabitsch, M., Hebebrand, J., and Hinney, A.
- Published
- 2012
4. GENE SET OF NUCLEAR ENCODED MITOCHONDRIAL REGULATORS IS ENRICHED FOR INHERITED VARIATION IN OBESITY: 490 accepted poster
- Author
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Knoll, N., Jarick, I., Scherag, A., Volckmar, A. L., Scherag, S., Klingenspor, M., Illig, T., Grallert, H., Wichmann, H. E., Peters, A., Hebebrand, J., and Hinney, A.
- Published
- 2012
5. Quality control and conduct of genome-wide association meta-analyses
- Author
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Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis GR, Absher D, Alavere H, Albrecht E, Allen HL, Almgren P, Amin N, Amouyel P, Anderson D, Arnold AM, Arveiler D, Aspelund T, Asselbergs FW, Assimes TL, Atalay M, Attwood AP, Atwood LD, Bakker SJ, Balkau B, Balmforth AJ, Barlassina C, Barroso I, Basart H, Bauer S, Beckmann JS, Beilby JP, Bennett AJ, Ben Shlomo Y, Bergman RN, Bergmann S, Berndt SI, Biffar R, Di Blasio AM, Boehm BO, Boehnke M, Boeing H, Boerwinkle E, Bolton JL, Bonnefond A, Bonnycastle LL, Boomsma DI, Borecki IB, Bornstein SR, Bouatia Naji N, Boucher G, Bragg Gresham JL, BRAMBILLA, PAOLO, Bruinenberg M, Buchanan TA, Buechler C, Cadby G, Campbell H, Caulfield MJ, Cavalcanti Proença C, CESANA, GIANCARLO, Chanock SJ, Chasman DI, Chen YD, Chines PS, Clegg DJ, Coin L, Collins FS, Connell JM, Cookson W, Cooper MN, Croteau Chonka DC, Cupples LA, Cusi D, Day FR, Day IN, Dedoussis GV, Dei M, Deloukas P, Dermitzakis ET, Dimas AS, Dimitriou M, Dixon AL, Dörr M, van Duijn CM, Ebrahim S, Edkins S, Eiriksdottir G, Eisinger K, Eklund N, Elliott P, Erbel R, Erdmann J, Erdos MR, Eriksson JG, Esko T, Estrada K, Evans DM, de Faire U, Fall T, Farrall M, Feitosa MF, Ferrario MM, Ferreira T, Ferrières J, Fischer K, Fisher E, Fowkes G, Fox CS, Franke L, Franks PW, Fraser RM, Frau F, Frayling T, Freimer NB, Froguel P, Fu M, Gaget S, Ganna A, Gejman PV, Gentilini D, Geus EJ, Gieger C, Gigante B, Gjesing AP, Glazer NL, Goddard ME, Goel A, Grallert H, Gräßler J, Grönberg H, Groop LC, Groves CJ, Gudnason V, Guiducci C, Gustafsson S, Gyllensten U, Hall AS, Hall P, Hallmans G, Hamsten A, Hansen T, Haritunians T, Harris TB, van der Harst P, Hartikainen AL, Hassanali N, Hattersley AT, Havulinna AS, Hayward C, Heard Costa NL, Heath AC, Hebebrand J, Heid IM, den Heijer M, Hengstenberg C, Herzig KH, Hicks AA, Hingorani A, Hinney A, Hirschhorn JN, Hofman A, Holmes CC, Homuth G, Hottenga JJ, Hovingh KG, Hu FB, Hu YJ, Huffman JE, Hui J, Huikuri H, Humphries SE, Hung J, Hunt SE, Hunter D, Hveem K, Hyppönen E, Igl W, Illig T, Ingelsson E, Iribarren C, Isomaa B, Jackson AU, Jacobs KB, James AL, Jansson JO, Jarick I, Jarvelin MR, Jöckel KH, Johansson Å, Johnson T, Jolley J, Jørgensen T, Jousilahti P, Jula A, Justice AE, Kaakinen M, Kähönen M, Kajantie E, Kanoni S, Kao WH, Kaplan LM, Kaplan RC, Kaprio J, Kapur K, Karpe F, Kathiresan S, Kee F, Keinanen Kiukaanniemi SM, Ketkar S, Kettunen J, Khaw KT, Kiemeney LA, Kilpeläinen TO, Kinnunen L, Kivimaki M, Kivmaki M, Van der Klauw MM, Kleber ME, Knowles JW, Koenig W, Kolcic I, Kolovou G, König IR, Koskinen S, Kovacs P, Kraft P, Kraja AT, Kristiansson K, KrjutÅjkov K, Kroemer HK, Krohn JP, Krzelj V, Kuh D, Kulzer JR, Kumari M, Kutalik Z, Kuulasmaa K, Kuusisto J, Kvaloy K, Laakso M, Laitinen JH, Lakka TA, Lamina C, Langenberg C, Lantieri O, Lathrop GM, Launer LJ, Lawlor DA, Lawrence RW, Leach IM, Lecoeur C, Lee SH, Lehtimäki T, Leitzmann MF, Lettre G, Levinson DF, Li G, Li S, Liang L, Lin DY, Lind L, Lindgren CM, Lindström J, Liu J, Liuzzi A, Locke AE, Lokki ML, Loley C, Loos RJ, Lorentzon M, Luan J, Luben RN, Ludwig B, Madden PA, Mägi R, Magnusson PK, Mangino M, Manunta P, Marek D, Marre M, Martin NG, März W, Maschio A, Mathieson I, McArdle WL, McCaroll SA, McCarthy A, McCarthy MI, McKnight B, Medina Gomez C, Medland SE, Meitinger T, Metspalu A, van Meurs JB, Meyre D, Midthjell K, Mihailov E, Milani L, Min JL, Moebus S, Moffatt MF, Mohlke KL, Molony C, Monda KL, Montgomery GW, Mooser V, Morken MA, Morris AD, Morris AP, Mühleisen TW, Müller Nurasyid M, Munroe PB, Musk AW, Narisu N, Navis G, Neale BM, Nelis M, Nemesh J, Neville MJ, Ngwa JS, Nicholson G, Nieminen MS, Njølstad I, Nohr EA, Nolte IM, North KE, Nöthen MM, Nyholt DR, O'Connell JR, Ohlsson C, Oldehinkel AJ, van Ommen GJ, Ong KK, Oostra BA, Ouwehand WH, Palmer CN, Palmer LJ, Palotie A, Paré G, Parker AN, Paternoster L, Pawitan Y, Pechlivanis S, Peden JF, Pedersen NL, Pedersen O, Pellikka N, Peltonen L, Penninx B, Perola M, Perry JR, Person T, Peters A, Peters MJ, Pichler I, Pietiläinen KH, Platou CG, Polasek O, Pouta A, Power C, Pramstaller PP, Preuss M, Price JF, Prokopenko I, Province MA, Psaty BM, Purcell S, Pütter C, Qi L, Quertermous T, Radhakrishnan A, Raitakari O, Randall JC, Rauramaa R, Rayner NW, Rehnberg E, Rendon A, Ridderstråle M, Ridker PM, Ripatti S, Rissanen A, Rivadeneira F, Rivolta C, Robertson NR, Rose LM, Rudan I, Saaristo TE, Sager H, Salomaa V, Samani NJ, Sambrook JG, Sanders AR, Sandholt C, Sanna S, Saramies J, Schadt EE, Scherag A, Schipf S, Schlessinger D, Schreiber S, Schunkert H, Schwarz PE, Scott LJ, Shi J, Shin SY, Shuldiner AR, Shungin D, Signorini S, Silander K, Sinisalo J, Skrobek B, Smit JH, Smith AV, Smith GD, Snieder H, Soranzo N, Sørensen TI, Sovio U, Spector TD, Speliotes EK, Stančáková A, Stark K, Stefansson K, Steinthorsdottir V, Stephens JC, Stirrups K, Stolk RP, Strachan DP, Strawbridge RJ, Stringham HM, Stumvoll M, Surakka I, Swift AJ, Syvanen AC, Tammesoo ML, Teder Laving M, Teslovich TM, Teumer A, Theodoraki EV, Thomson B, Thorand B, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tönjes A, Tregouet DA, Tremoli E, Trip MD, Tuomi T, Tuomilehto J, Tyrer J, Uda M, Uitterlinden AG, Usala G, Uusitupa M, Valle TT, Vandenput L, Vatin V, Vedantam S, de Vegt F, Vermeulen SH, Viikari J, Virtamo J, Visscher PM, Vitart V, Van Vliet Ostaptchouk JV, Voight BF, Vollenweider P, Volpato CB, Völzke H, Waeber G, Waite LL, Wallaschofski H, Walters GB, Wang Z, Wareham NJ, Watanabe RM, Watkins H, Weedon MN, Welch R, Weyant RJ, Wheeler E, White CC, Wichmann HE, Widen E, Wild SH, Willemsen G, Willer CJ, Wilsgaard T, Wilson JF, van Wingerden S, Winkelmann BR, Winkler TW, Witte DR, Witteman JC, Wolffenbuttel BH, Wong A, Wood AR, Workalemahu T, Wright AF, Yang J, Yarnell JW, Zgaga L, Zhao JH, Zillikens MC, Zitting P, Zondervan KT, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis, G, Absher, D, Alavere, H, Albrecht, E, Allen, H, Almgren, P, Amin, N, Amouyel, P, Anderson, D, Arnold, A, Arveiler, D, Aspelund, T, Asselbergs, F, Assimes, T, Atalay, M, Attwood, A, Atwood, L, Bakker, S, Balkau, B, Balmforth, A, Barlassina, C, Barroso, I, Basart, H, Bauer, S, Beckmann, J, Beilby, J, Bennett, A, Ben Shlomo, Y, Bergman, R, Bergmann, S, Berndt, S, Biffar, R, Di Blasio, A, Boehm, B, Boehnke, M, Boeing, H, Boerwinkle, E, Bolton, J, Bonnefond, A, Bonnycastle, L, Boomsma, D, Borecki, I, Bornstein, S, Bouatia Naji, N, Boucher, G, Bragg Gresham, J, Brambilla, P, Bruinenberg, M, Buchanan, T, Buechler, C, Cadby, G, Campbell, H, Caulfield, M, Cavalcanti Proença, C, Cesana, G, Chanock, S, Chasman, D, Chen, Y, Chines, P, Clegg, D, Coin, L, Collins, F, Connell, J, Cookson, W, Cooper, M, Cupples, L, Cusi, D, Day, I, Dedoussis, G, Dei, M, Deloukas, P, Dermitzakis, E, Dimas, A, Dimitriou, M, Dixon, A, Dörr, M, van Duijn, C, Ebrahim, S, Edkins, S, Eiriksdottir, G, Eisinger, K, Eklund, N, Elliott, P, Erbel, R, Erdmann, J, Erdos, M, Eriksson, J, Estrada, K, Evans, D, de Faire, U, Farrall, M, Feitosa, M, Ferrario, M, Ferrières, J, Fischer, K, Fisher, E, Fowkes, G, Fox, C, Franke, L, Franks, P, Fraser, R, Frau, F, Frayling, T, Freimer, N, Froguel, P, Fu, M, Gaget, S, Ganna, A, Gejman, P, Gentilini, D, Geus, E, Gieger, C, Gigante, B, Gjesing, A, Glazer, N, Goddard, M, Goel, A, Grallert, H, Gräßler, J, Grönberg, H, Groop, L, Groves, C, Gudnason, V, Guiducci, C, Gyllensten, U, Hall, A, Hall, P, Hallmans, G, Hamsten, A, Hansen, T, Haritunians, T, Harris, T, van der Harst, P, Hartikainen, A, Hassanali, N, Hattersley, A, Havulinna, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, den Heijer, M, Hengstenberg, C, Herzig, K, Hicks, A, Hingorani, A, Hinney, A, Hirschhorn, J, Hofman, A, Holmes, C, Homuth, G, Hottenga, J, Hovingh, K, Hu, F, Hu, Y, Huffman, J, Hui, J, Huikuri, H, Humphries, S, Hung, J, Hunt, S, Hunter, D, Hveem, K, Hyppönen, E, Igl, W, Illig, T, Ingelsson, E, Iribarren, C, Isomaa, B, Jackson, A, Jacobs, K, James, A, Jansson, J, Jarick, I, Jarvelin, M, Jöckel, K, Johansson, Å, Johnson, T, Jolley, J, Jørgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kähönen, M, Kajantie, E, Kanoni, S, Kao, W, Kaplan, L, Kaplan, R, Kaprio, J, Kapur, K, Karpe, F, Kathiresan, S, Kee, F, Keinanen Kiukaanniemi, S, Ketkar, S, Kettunen, J, Khaw, K, Kiemeney, L, Kinnunen, L, Kivimaki, M, Kivmaki, M, Van der Klauw, M, Kleber, M, Knowles, J, Koenig, W, Kolcic, I, Kolovou, G, König, I, Koskinen, S, Kovacs, P, Kraft, P, Kraja, A, Kristiansson, K, Krjutåjkov, K, Kroemer, H, Krohn, J, Krzelj, V, Kuh, D, Kulzer, J, Kumari, M, Kuulasmaa, K, Kuusisto, J, Kvaloy, K, Laakso, M, Laitinen, J, Lakka, T, Lamina, C, Langenberg, C, Lantieri, O, Lathrop, G, Launer, L, Lawlor, D, Lawrence, R, Leach, I, Lecoeur, C, Lee, S, Lehtimäki, T, Leitzmann, M, Lettre, G, Levinson, D, Li, G, Li, S, Liang, L, Lin, D, Lind, L, Lindgren, C, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Loley, C, Lorentzon, M, Luben, R, Ludwig, B, Madden, P, Magnusson, P, Mangino, M, Manunta, P, Marek, D, Marre, M, Martin, N, März, W, Maschio, A, Mathieson, I, Mcardle, W, Mccaroll, S, Mccarthy, A, Mccarthy, M, Mcknight, B, Medina Gomez, C, Medland, S, Meitinger, T, Metspalu, A, van Meurs, J, Meyre, D, Midthjell, K, Mihailov, E, Milani, L, Min, J, Moebus, S, Moffatt, M, Mohlke, K, Molony, C, Monda, K, Montgomery, G, Mooser, V, Morken, M, Morris, A, Mühleisen, T, Müller Nurasyid, M, Munroe, P, Musk, A, Narisu, N, Navis, G, Neale, B, Nelis, M, Nemesh, J, Neville, M, Ngwa, J, Nicholson, G, Nieminen, M, Njølstad, I, Nohr, E, Nolte, I, North, K, Nöthen, M, Nyholt, D, O'Connell, J, Ohlsson, C, Oldehinkel, A, van Ommen, G, Ong, K, Oostra, B, Ouwehand, W, Palmer, C, Palmer, L, Palotie, A, Paré, G, Parker, A, Paternoster, L, Pawitan, Y, Pechlivanis, S, Peden, J, Pedersen, N, Pedersen, O, Pellikka, N, Peltonen, L, Penninx, B, Perola, M, Perry, J, Person, T, Peters, A, Peters, M, Pichler, I, Pietiläinen, K, Platou, C, Polasek, O, Pouta, A, Power, C, Pramstaller, P, Preuss, M, Price, J, Prokopenko, I, Province, M, Psaty, B, Purcell, S, Pütter, C, Qi, L, Quertermous, T, Radhakrishnan, A, Raitakari, O, Rauramaa, R, Rayner, N, Rehnberg, E, Rendon, A, Ridderstråle, M, Ridker, P, Ripatti, S, Rissanen, A, Rivadeneira, F, Rivolta, C, Robertson, N, Rose, L, Rudan, I, Saaristo, T, Sager, H, Salomaa, V, Samani, N, Sambrook, J, Sanders, A, Sandholt, C, Sanna, S, Saramies, J, Schadt, E, Schipf, S, Schlessinger, D, Schreiber, S, Schunkert, H, Schwarz, P, Scott, L, Shi, J, Shin, S, Shuldiner, A, Shungin, D, Signorini, S, Silander, K, Sinisalo, J, Skrobek, B, Smit, J, Smith, A, Smith, G, Snieder, H, Soranzo, N, Sørensen, T, Sovio, U, Spector, T, Speliotes, E, Stančáková, A, Stark, K, Stefansson, K, Steinthorsdottir, V, Stephens, J, Stirrups, K, Stolk, R, Strachan, D, Strawbridge, R, Stringham, H, Stumvoll, M, Surakka, I, Swift, A, Syvanen, A, Tammesoo, M, Teder Laving, M, Teslovich, T, Teumer, A, Theodoraki, E, Thomson, B, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Timpson, N, Tönjes, A, Tregouet, D, Tremoli, E, Trip, M, Tuomi, T, Tuomilehto, J, Tyrer, J, Uda, M, Uitterlinden, A, Usala, G, Uusitupa, M, Valle, T, Vandenput, L, Vatin, V, de Vegt, F, Vermeulen, S, Viikari, J, Virtamo, J, Visscher, P, Vitart, V, Van Vliet Ostaptchouk, J, Voight, B, Vollenweider, P, Volpato, C, Völzke, H, Waeber, G, Waite, L, Wallaschofski, H, Walters, G, Wang, Z, Wareham, N, Watanabe, R, Watkins, H, Weedon, M, Welch, R, Weyant, R, Wheeler, E, White, C, Wichmann, H, Widen, E, Wild, S, Willemsen, G, Willer, C, Wilsgaard, T, Wilson, J, van Wingerden, S, Winkelmann, B, Witte, D, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Yang, J, Yarnell, J, Zgaga, L, Zhao, J, Zillikens, M, Zitting, P, Zondervan, K, Psychiatry, EMGO - Mental health, Plastic, Reconstructive and Hand Surgery, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Biological Psychology, EMGO+ - Mental Health, Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Abecasis, GR., Absher, D., Alavere, H., Albrecht, E., Allen, HL., Almgren, P., Amin, N., Amouyel, P., Anderson, D., Arnold, AM., Arveiler, D., Aspelund, T., Asselbergs, FW., Assimes, TL., Atalay, M., Attwood, AP., Atwood, LD., Bakker, SJ., Balkau, B., Balmforth, AJ., Barlassina, C., Barroso£££Inês£££ I., Basart, H., Bauer, S., Beckmann, JS., Beilby, JP., Bennett, AJ., Ben-Shlomo, Y., Bergman, RN., Bergmann, S., Berndt, SI., Biffar, R., Di Blasio AM., Boehm, BO., Boehnke, M., Boeing, H., Boerwinkle, E., Bolton, JL., Bonnefond, A., Bonnycastle, LL., Boomsma, DI., Borecki, IB., Bornstein, SR., Bouatia-Naji, N., Boucher, G., Bragg-Gresham, JL., Brambilla, P., Bruinenberg, M., Buchanan, TA., Buechler, C., Cadby, G., Campbell, H., Caulfield, MJ., Cavalcanti-Proença, C., Cesana, G., Chanock, SJ., Chasman, DI., Chen, YD., Chines, PS., Clegg, DJ., Coin, L., Collins, FS., Connell, JM., Cookson, W., Cooper, MN., Croteau-Chonka, DC., Cupples, LA., Cusi, D., Day, FR., Day, IN., Dedoussis, GV., Dei, M., Deloukas, P., Dermitzakis, ET., Dimas, AS., Dimitriou, M., Dixon, AL., Dörr, M., van Duijn CM., Ebrahim, S., Edkins, S., Eiriksdottir, G., Eisinger, K., Eklund, N., Elliott, P., Erbel, R., Erdmann, J., Erdos, MR., Eriksson, JG., Esko£££Tõnu£££ T., Estrada, K., Evans, DM., de Faire, U., Fall, T., Farrall, M., Feitosa, MF., Ferrario, MM., Ferreira, T., Ferrières, J., Fischer, K., Fisher, E., Fowkes, G., Fox, CS., Franke, L., Franks, PW., Fraser, RM., Frau, F., Frayling, T., Freimer, NB., Froguel, P., Fu, M., Gaget, S., Ganna, A., Gejman, PV., Gentilini, D., Geus, EJ., Gieger, C., Gigante, B., Gjesing, AP., Glazer, NL., Goddard, ME., Goel, A., Grallert, H., Gräßler, J., Grönberg, H., Groop, LC., Groves, CJ., Gudnason, V., Guiducci, C., Gustafsson, S., Gyllensten, U., Hall, AS., Hall, P., Hallmans, G., Hamsten, A., Hansen, T., Haritunians, T., Harris, TB., van der Harst, P., Hartikainen, AL., Hassanali, N., Hattersley, AT., Havulinna, AS., Hayward, C., Heard-Costa, NL., Heath, AC., Hebebrand, J., Heid, IM., den Heijer, M., Hengstenberg, C., Herzig, KH., Hicks, AA., Hingorani, A., Hinney, A., Hirschhorn, JN., Hofman, A., Holmes, CC., Homuth, G., Hottenga, JJ., Hovingh, KG., Hu, FB., Hu, YJ., Huffman, JE., Hui, J., Huikuri, H., Humphries, SE., Hung, J., Hunt, SE., Hunter, D., Hveem, K., Hyppönen, E., Igl, W., Illig, T., Ingelsson, E., Iribarren, C., Isomaa, B., Jackson, AU., Jacobs, KB., James, AL., Jansson, JO., Jarick, I., Jarvelin, MR., Jöckel, KH., Johansson£££Åsa£££ Å., Johnson, T., 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Locke, AE., Lokki, ML., Loley, C., Loos, RJ., Lorentzon, M., Luan£££Jian'an£££ J., Luben, RN., Ludwig, B., Madden, PA., Mägi, R., Magnusson, PK., Mangino, M., Manunta, P., Marek, D., Marre, M., Martin, NG., März, W., Maschio, A., Mathieson, I., McArdle, WL., McCaroll, SA., McCarthy, A., McCarthy, MI., McKnight, B., Medina-Gomez, C., Medland, SE., Meitinger, T., Metspalu, A., van Meurs JB., Meyre, D., Midthjell, K., Mihailov, E., Milani, L., Min, JL., Moebus, S., Moffatt, MF., Mohlke, KL., Molony, C., Monda, KL., Montgomery, GW., Mooser, V., Morken, MA., Morris, AD., Morris, AP., Mühleisen, TW., Müller-Nurasyid, M., Munroe, PB., Musk, AW., Narisu, N., Navis, G., Neale, BM., Nelis, M., Nemesh, J., Neville, MJ., Ngwa, JS., Nicholson, G., Nieminen, MS., Njølstad, I., Nohr, EA., Nolte, IM., North, KE., Nöthen, MM., Nyholt, DR., O'Connell, JR., Ohlsson, C., Oldehinkel, AJ., van Ommen GJ., Ong, KK., Oostra, BA., Ouwehand, WH., Palmer, CN., Palmer, LJ., Palotie, A., Paré, G., Parker, AN., Paternoster, L., Pawitan, Y., Pechlivanis, S., Peden, JF., Pedersen, NL., Pedersen, O., Pellikka, N., Peltonen, L., Penninx, B., Perola, M., Perry, JR., Person, T., Peters, A., Peters, MJ., Pichler, I., Pietiläinen, KH., Platou, CG., Polasek, O., Pouta, A., Power, C., Pramstaller, PP., Preuss, M., Price, JF., Prokopenko, I., Province, MA., Psaty, BM., Purcell, S., Pütter, C., Qi, L., Quertermous, T., Radhakrishnan, A., Raitakari, O., Randall, JC., Rauramaa, R., Rayner, NW., Rehnberg, E., Rendon, A., Ridderstråle, M., Ridker, PM., Ripatti, S., Rissanen, A., Rivadeneira, F., Rivolta, C., Robertson, NR., Rose, LM., Rudan, I., Saaristo, TE., Sager, H., Salomaa, V., Samani, NJ., Sambrook, JG., Sanders, AR., Sandholt, C., Sanna, S., Saramies, J., Schadt, EE., Scherag, A., Schipf, S., Schlessinger, D., Schreiber, S., Schunkert, H., Schwarz, PE., Scott, LJ., Shi, J., Shin, SY., Shuldiner, AR., Shungin, D., Signorini, S., Silander, K., Sinisalo, J., Skrobek, B., Smit, JH., Smith, AV., Smith, GD., Snieder, H., Soranzo, N., Sørensen, TI., Sovio, U., Spector, TD., Speliotes, EK., Stančáková, A., Stark, K., Stefansson, K., Steinthorsdottir, V., Stephens, JC., Stirrups, K., Stolk, RP., Strachan, DP., Strawbridge, RJ., Stringham, HM., Stumvoll, M., Surakka, I., Swift, AJ., Syvanen, AC., Tammesoo, ML., Teder-Laving, M., Teslovich, TM., Teumer, A., Theodoraki, EV., Thomson, B., Thorand, B., Thorleifsson, G., Thorsteinsdottir, U., Timpson, NJ., Tönjes, A., Tregouet, DA., Tremoli, E., Trip, MD., Tuomi, T., Tuomilehto, J., Tyrer, J., Uda, M., Uitterlinden, AG., Usala, G., Uusitupa, M., Valle, TT., Vandenput, L., Vatin, V., Vedantam, S., de Vegt, F., Vermeulen, SH., Viikari, J., Virtamo, J., Visscher, PM., Vitart, V., Van Vliet-Ostaptchouk JV., Voight, BF., Vollenweider, P., Volpato, CB., Völzke, H., Waeber, G., Waite, LL., Wallaschofski, H., Walters, GB., Wang, Z., Wareham, NJ., Watanabe, RM., Watkins, H., Weedon, MN., Welch, R., Weyant, RJ., Wheeler, E., White, CC., Wichmann, HE., Widen, E., Wild, SH., Willemsen, G., Willer, CJ., Wilsgaard, T., Wilson, JF., van Wingerden, S., Winkelmann, BR., Winkler, TW., Witte, DR., Witteman, JC., Wolffenbuttel, BH., Wong, A., Wood, AR., Workalemahu, T., Wright, AF., Yang, J., Yarnell, JW., Zgaga, L., Zhao, JH., Zillikens, MC., Zitting, P., and Zondervan, KT.
- Subjects
Quality Control ,Netherlands Twin Register (NTR) ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,media_common.quotation_subject ,quality control, GWAMAS ,Control (management) ,Medizin ,Genome-wide association study ,Biology ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Software ,SDG 17 - Partnerships for the Goals ,Meta-Analysis as Topic ,Comparable size ,Quality (business) ,030304 developmental biology ,media_common ,Protocol (science) ,0303 health sciences ,business.industry ,Software package ,Data science ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Genome-Wide Association Study/methods ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,quality control ,genome-wide association meta-analyses ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Item does not contain fulltext Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.
- Published
- 2014
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6. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index
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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
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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
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- 2017
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7. Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index
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Hoggart, C, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, J, Teumer, A, Winkler, T, Tšernikova, N, Luan, J, Mihailov, E, Ehret, G, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, P, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, D, Hayward, C, Lopez, M, Franke, L, Russo, A, Heid, I, Salvi, E, Vendantam, S, Arking, D, Boerwinkle, E, Chambers, J, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, J, Porteous, D, Berg, J, Blackwood, D, Campbell, H, Cavanagh, J, Connell, J, Connor, M, Cunningham Burley, S, Deary, I, Dominiczak, A, Ellis, P, Fitzpatrick, B, Ford, I, Gertz, R, Grau, A, Haddow, G, Jackson, C, Kerr, S, Lindsay, R, Mcgilchrist, M, Mcintyre, D, Morris, A, Morton, R, Muir, W, Murray, G, Palmer, C, Pell, J, Philp, A, Porteous, M, Procter, R, Ralston, S, Reid, D, Sinnott, R, Smith, B, St Clair, D, Sullivan, F, Sweetland, M, Ure, J, Watt, G, Wolf, R, Wright, A, de Bakker, P, Bültmann, U, Geleijnse, M, Harst, P, Koppelman, G, Rosmalen, J, van Rossum, L, Smidt, H, Swertz, M, Stolk, R, Alizadeh, B, de Boer, R, Boezen, H, Bruinenberg, M, van der Harst, P, Hillege, H, van der Klauw, M, Navis, G, Ormel, J, Postma, D, Slaets, J, Snieder, H, Wolffenbuttel, B, Wijmenga, C, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Randall, J, Vedantam, S, Willer, C, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Jarick, I, Johansson, A, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, BRAMBILLA, PAOLO, Chasman, D, Chines, P, Collins, F, Cookson, W, de Faire, U, de Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Farrall, M, Ferrario, M, Ferrières, J, Frau, F, Gejman, P, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Heard Costa, N, Heath, A, Hebebrand, J, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimaki, M, Koenig, W, Kraja, A, Kumari, M, Karikuulasmaa, N, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Leach, I, Mcknight, B, Medland, S, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stancakova, A, Stark, K, Stephens, J, Stirrups, K, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widen, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wong, A, Zillikens, M, Amouyel, P, Boehm, B, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Hunter, D, Kaplan, R, Karpe, F, Miriammoffatt, N, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, van Duijn, C, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Moradpour, D, Iranzo, A, Kemp, J, Lammers, G, Aubert, V, Heim, M, Peraita Adrados, R, Santamaria, J, Negro, F, Schmidt, C, Scott, R, Strauch, K, Völzke, H, Yuan, W, Bell, J, Chakravarti, A, Kooner, J, Matullo, G, Whitfield, J, Paccaud, F, Bergmann, S, Beckmann, J, Tafti, M, Hastie, N, Bochud, M, Da Smith, G, Rousson, V, Rivolta, C, Kutalik, Z., Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Hoggart, Clive J, Venturini, Giulia, Mangino, Massimo, Gomez, Felicia, Benyamin, Beben, Kutalik, Zoltan, Generation Scotland Consortium, GIANT Consortium, LifeLines Cohort study, Cardiology, Vascular Medicine, Plastic, Reconstructive and Hand Surgery, Amsterdam Cardiovascular Sciences, Medical Research Council (MRC), Psychiatry, EMGO - Lifestyle, overweight and diabetes, Haartman Institute (-2014), Transplantation Laboratory, Luan, Jian'an [0000-0003-3137-6337], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Hoggart, Cj, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, Jh, Teumer, A, Winkler, Tw, Tšernikova, N, Luan, J, Mihailov, E, Ehret, Gb, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, Py, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, Dm, Hayward, C, Lopez, Mf, Franke, L, Russo, A, Heid, Im, Salvi, E, Vendantam, S, Arking, De, Boerwinkle, E, Chambers, Jc, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, Je, Porteous, D, GENERATION SCOTLAND, Consortium, LIFELINES COHORT, Study, Giant, Consortium, Manunta, Paolo, Moradpour, D, Iranzo, A, Hebebrand, J, Kemp, Jp, Lammers, Gj, Aubert, V, Heim, Mh, Martin, Ng, Montgomery, Gw, PERAITA ADRADOS, R, Santamaria, J, Negro, F, Schmidt, Co, Scott, Ra, Spector, Td, Strauch, K, Völzke, H, Wareham, Nj, Yuan, W, Bell, Jt, Chakravarti, A, Kooner, J, Peters, A, Matullo, G, Wallaschofski, H, Whitfield, Jb, Paccaud, F, Vollenweider, P, Bergmann, S, Beckmann, J, Tafti, M, Hastie, Nd, Cusi, D, Bochud, M, Frayling, Tm, Metspalu, A, Jarvelin, Mr, Scherag, A, Smith, Gd, Borecki, Ib, Rousson, V, Hirschhorn, Jn, Rivolta, C, Loos, Rj, Kutalik, Z., Hoggart, C, Zhao, J, Winkler, T, Ehret, G, Bochud, P, Evans, D, Lopez, M, Heid, I, Arking, D, Chambers, J, Huffman, J, Berg, J, Blackwood, D, Campbell, H, Cavanagh, J, Connell, J, Connor, M, Cunningham Burley, S, Deary, I, Dominiczak, A, Ellis, P, Fitzpatrick, B, Ford, I, Gertz, R, Grau, A, Haddow, G, Jackson, C, Kerr, S, Lindsay, R, Mcgilchrist, M, Mcintyre, D, Morris, A, Morton, R, Muir, W, Murray, G, Palmer, C, Pell, J, Philp, A, Porteous, M, Procter, R, Ralston, S, Reid, D, Sinnott, R, Smith, B, St Clair, D, Sullivan, F, Sweetland, M, Ure, J, Watt, G, Wolf, R, Wright, A, de Bakker, P, Bültmann, U, Geleijnse, M, Harst, P, Koppelman, G, Rosmalen, J, van Rossum, L, Smidt, H, Swertz, M, Stolk, R, Alizadeh, B, de Boer, R, Boezen, H, Bruinenberg, M, van der Harst, P, Hillege, H, van der Klauw, M, Navis, G, Ormel, J, Postma, D, Slaets, J, Snieder, H, Wolffenbuttel, B, Wijmenga, C, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Randall, J, Vedantam, S, Willer, C, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Jarick, I, Johansson, A, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Chasman, D, Chines, P, Collins, F, Cookson, W, de Faire, U, de Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Farrall, M, Ferrario, M, Ferrières, J, Frau, F, Gejman, P, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Heard Costa, N, Heath, A, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimaki, M, Koenig, W, Kraja, A, Kumari, M, Karikuulasmaa, N, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Leach, I, Mcknight, B, Medland, S, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palotie, A, Peden, J, Pedersen, N, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stancakova, A, Stark, K, Stephens, J, Stirrups, K, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widen, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wong, A, Zillikens, M, Amouyel, P, Boehm, B, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Hunter, D, Kaplan, R, Karpe, F, Miriammoffatt, N, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, van Duijn, C, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Kemp, J, Lammers, G, Heim, M, Peraita Adrados, R, Schmidt, C, Scott, R, Bell, J, Whitfield, J, Hastie, N, and Da Smith, G
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Epigenomics ,Male ,Netherlands Twin Register (NTR) ,body mass index ,gene ,SNP ,Cancer Research ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Potassium Channels ,Glucose Transport Proteins, Facilitative ,Medizin ,Genome-wide association study ,CHILDREN ,ddc:616.07 ,FAMILIES ,Body Mass Index ,0302 clinical medicine ,Polymorphism (computer science) ,Genotype ,LifeLines Cohort study ,GENETICS & HEREDITY ,Tandem Pore Domain ,Genetics (clinical) ,ASSOCIATIONS ,ddc:616 ,Genetics ,0303 health sciences ,QUANTITATIVE TRAIT LOCI ,Ecology ,Genomics ,Single Nucleotide ,Generation Scotland Consortium ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,OBESITY ,Physical Sciences ,KCNK9 protein ,Epigenetics ,Female ,ALCOHOLISM ,Glucose Transport Proteins ,Life Sciences & Biomedicine ,Statistics (Mathematics) ,Human ,Research Article ,VARIANCES ,Adult ,PENETRANCE ,GENES ,lcsh:QH426-470 ,Evolution ,European Continental Ancestry Group ,Single-nucleotide polymorphism ,Biostatistics ,Biology ,Quantitative trait locus ,Polymorphism, Single Nucleotide ,White People ,03 medical and health sciences ,Genomic Imprinting ,Potassium Channels, Tandem Pore Domain ,Genetic ,Behavior and Systematics ,SDG 3 - Good Health and Well-being ,Genetic linkage ,GIANT Consortium ,Genome-Wide Association Studies ,Humans ,Genetic Predisposition to Disease ,Statistical Methods ,Allele ,Polymorphism ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Gene Expression Regulation ,Genome-Wide Association Study ,Obesity ,030304 developmental biology ,0604 Genetics ,Science & Technology ,LINKAGE ANALYSIS ,SLC2A10 protein ,Biology and Life Sciences ,Computational Biology ,Facilitative ,Genome Analysis ,Ecology, Evolution, Behavior and Systematic ,lcsh:Genetics ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,3111 Biomedicine ,Genomic imprinting ,Mathematics ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P, Author Summary Large genetic association studies have revealed many genetic factors influencing common traits, such as body mass index (BMI). These studies assume that the effect of genetic variants is the same regardless of whether they are inherited from the mother or the father. In our study, we have developed a new approach that allows us to investigate variants whose impact depends on their parental origin (parent-of-origin effects), in unrelated samples when the parental origin cannot be inferred. This is feasible because at genetic markers at which such effects occur there is increased variability of the trait among individuals who inherited different genetic codes from their mother and their father compared to individuals who inherited the same genetic code from both parents. We applied this methodology to discover genetic markers with parent-of-origin effects (POEs) on BMI. This resulted in six candidate markers showing strong POE association. We then attempted to replicate the POE effects of these markers in family studies (where one can infer the parental origin of the inherited variants). Two of our candidates showed significant association in the family studies, the paternal and maternal effects of these markers were in the opposite direction.
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- 2014
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8. Beneficial Metabolic Effects of Duodenal Jejunal Bypass Liner for the Treatment of Adipose Patients with Type 2 Diabetes Mellitus: Analysis of Responders and Non-Responders
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Stratmann, B., additional, Krepak, Y., additional, Schiffer, E., additional, Jarick, I., additional, Hauber, M., additional, Lee-Barkey, Y., additional, Fischer, M., additional, and Tschoepe, D., additional
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- 2016
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9. Метаанализ геномных ассоциаций выявил новые локусы, ассоциированные с ожирением у детей
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Bradfield, Jp, Taal, Hr, Timpson, Nj, Scherag, A., Lecoeur, C., Warrington, Nm, Hypponen, E., Holst, C., Valcarcel, B., Thiering, E., Salem, Rm, Schumacher, Fr, Cousminer, Dl, Sleiman, Pm, Zhao, J., Berkowitz, Ri, Vimaleswaran, Ks, Jarick, I., Pennell, Ce, Evans, Dm, St, Pourcain, Berry, Dj, Mook-kanamori, Do, Hofman, A., Rivadeneira, F., Uitterlinden, Ag, Van, Duijn, VAN DER VALK RJ, De, Jongste, Postma, Ds, Boomsma, Di, Gauderman, Wj, Hassanein, Mt, Lindgren, Cm, Mägi, R., Boreham, Ca, Neville, Ce, Moreno, La, Elliott, P., Pouta, A., Hartikainen, Al, Li, M., Raitakari, O., Lehtimäki, T., Eriksson, Jg, Palotie, A., Dallongeville, J., Das, S., Deloukas, P., Mcmahon, G., Ring, Sm, Kemp, Jp, Buxton, Jl, Blakemore, Ai, Bustamante, M., Guxens, M., Hirschhorn, Jn, Gillman, Mw, Kreiner-møller, E., Bisgaard, H., Gilliland, Fd, Heinrich, J., Wheeler, E., Barroso, I., O'rahilly, S., Meirhaeghe, A., Sørensen, Ti, Power, C., Palmer, Lj, Hinney, A., Widen, E., Farooqi, Is, Mccarthy, Mi, Froguel, P., Meyre, D., Hebebrand, J., Jarvelin, Mr, Jaddoe, Vw, Smith, Gd, Hakonarson, H., and Grant, Sf
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- 2012
10. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes
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Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, Bouatia Naji, N, Dimas, As, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, Cs, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, Kerr Conte, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, Martínez Larrad MT, Narisu, N, Nastase Mannila, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, van 't Hooft FM, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, Serrano Ríos, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, Fs, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, Voight BF, Florez J. C., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Bengtsson Boström, K, Bravenboer, B, Bumpstead, S, Burtt, P, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Franklin, Cs, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Nilsson, P, Owen, Kr, Perry, Jr, Petersen, K, Platou, C, Proença, C, Rathmann, W, William Rayner, N, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Thorand, B, Tichet, J, van Dam RM, van Haeften TW, van Herpt, T, van Vliet JV, Bragi Walters, G, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Pankow, Js, Pedersen, O, Wichmann, E, Florez, Jc, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Stefansson, K, Altshuler, D, Speliotes, Ek, Berndt, Si, Monda, Kl, Allen, Hl, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Workalemahu, T, Heid, Im, Wood, Ar, Weyant, Rj, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Kilpeläinen, To, Yang, J, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, Heard Costa NL, Hoesel, V, Hottenga, Jj, Johansson, Å, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Timpson, Nj, Tyrer, Jp, van Wingerden, S, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Arnold, Am, Aspelund, T, Atwood, Ld, Balmforth, Aj, Ben Shlomo, Y, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Cappuccio, Fp, Cavalcanti Proença, C, Ida Chen YD, Chen, Cm, Coin, L, Connell, J, Day, In, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Facheris, Mf, Felix, Sb, Fischer Posovszky, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gjesing, Ap, Goyette, P, Grässler, J, Greenawalt, Dm, Gudnason, V, Hartikainen, Al, Hall, As, Havulinna, As, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jousilahti, P, Jula, A, Kaakinen, M, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Terho, L, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, P, Marek, D, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Melander, O, Meyre, D, Montgomery, Gw, 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, 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, Tammesoo, Ml, Tardif, Jc, Teder Laving, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, van Meurs JB, van Ommen GJ, Vatin, V, Viikari, J, Visvikis Siest, S, Vitart, V, Vogel, Ci, 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, Dorret, I. B., Caulfield, Mj, Chanock, Sj, Cupples, La, Smith, Gd, Erdmann, J, Grönberg, H, Hall, P, Harris, Tb, Hayes, Rb, Heinrich, J, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Penninx, Bw, Peters, A, Quertermous, T, Reinehr, T, Rissanen, A, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Uda, M, Valle, Tt, Wabitsch, M, Waeber, G, Shaun, P, Eric, E. S., Peter, M. V., Assimes, Tl, Borecki, Ib, Groop, Lc, Haritunians, T, Kaplan, Rc, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, van Duijn CM, Barroso, H, North, Ke, Hirschhorn, Jn, Nica, Ac, Parts, L, Glass, D, Nisbet, J, Barrett, A, Sekowska, M, Travers, M, Potter, S, Grundberg, E, Small, K, Hedman, Åk, Bataille, V, Bell, Jt, Surdulescu, G, Ingle, C, Nestle, Fo, di Meglio, P, Min, Jl, Wilk, A, Hammond, Cj, Yang, Tp, Montgomery, Sb, Zondervan, Kt, Durbin, R, Ahmadi, K, Reilly, Mp, Holm, H, Stewart, Af, Barbalic, M, Absher, D, Aherrahrou, Z, Allayee, H, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Braund, Ps, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, El Mokhtari NE, Ellis, Sg, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Horne, Bd, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kastelein, Jj, Kolovou, G, Laaksonen, R, Lambrechts, D, Leander, K, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Sampietro, Ml, Schadt, E, Schäfer, A, Schillert, A, Schrezenmeir, J, Schwartz, Sm, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Spertus, Ja, Stark, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Wright, Bj, Ye, S, Zeller, T, Cambien, F, Goodall, Ah, März, W, Blankenberg, S, Roberts, R, Mcpherson, R, Nilesh, J. S., Medical Research Council (MRC), Nica, Alexandra, Ongen, Halit, Dermitzakis, Emmanouil, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Vascular Medicine, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Scherag, Andre (Beitragende*r), Hinney, Anke (Beitragende*r), Scherag, S. (Beitragende*r), Vogel, C (Beitragende*r), Hebebrand, Johannes (Beitragende*r), University of Groningen, Wheeler, Eleanor [0000-0002-8616-6444], Barnes, Daniel [0000-0002-3781-7570], Luan, Jian'an [0000-0003-3137-6337], Johnson, Kathleen [0000-0002-6823-3252], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository
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Male ,Netherlands Twin Register (NTR) ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Medizin ,Genome-wide association study ,Type 2 diabetes ,CORONARY HEART-DISEASE ,Fasting/blood ,0302 clinical medicine ,Insulin ,Glucose homeostasis ,ddc:576.5 ,Genome-wide ,Diabetes Mellitus, Type 2/blood/genetics/metabolism ,CARDIoGRAM Consortium ,POPULATION ,Proinsulin ,RISK ,Genetics ,0303 health sciences ,INSULIN SENSITIVITY ,11 Medical And Health Sciences ,Fasting ,Polymorphism, Single Nucleotide/genetics ,OBESITY ,Female ,type 2 diabetes ,Life Sciences & Biomedicine ,hormones, hormone substitutes, and hormone antagonists ,Insulin processing ,Adult ,medicine.medical_specialty ,endocrine system ,ENDOCRINOLOGY & METABOLISM ,SUSCEPTIBILITY LOCI ,Genotype ,030209 endocrinology & metabolism ,DIAGRAM Consortium ,Biology ,C4D Consortium ,Polymorphism, Single Nucleotide ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,Insulin resistance ,BETA-CELL FUNCTION ,SDG 3 - Good Health and Well-being ,Internal medicine ,GIANT Consortium ,Internal Medicine ,medicine ,Humans ,METAANALYSIS ,030304 developmental biology ,Science & Technology ,Genome, Human ,Hormonal regulation [IGMD 6] ,Genetic Variation ,nutritional and metabolic diseases ,proinsulin ,medicine.disease ,Proinsulin/blood ,TCF7L2 ,Endocrinology ,Diabetes Mellitus, Type 2 ,MuTHER Consortium ,GLUCOSE-HOMEOSTASIS ,Insulin/blood - Abstract
OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.
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- 2011
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11. Evaluating the role of reference models in copy number variation analyses
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Jarick, I, Hinney, A, Hebebrand, J, and Schäfer, H
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ddc: 610 ,endocrine system diseases ,mental disorders ,610 Medical sciences ,Medicine - Abstract
Besides single nucleotide polymorphisms (SNPs), copy number variations (CNVs) as another important component of genomic variation have gained much attention with regard to human phenotypic diversity. CNVs, being defined as segments of DNA that are larger than 1 kb in size and that are present at variable[for full text, please go to the a.m. URL], Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi)
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- 2011
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12. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes
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Strawbridge, R.J. Dupuis, J. Prokopenko, I. Barker, A. Ahlqvist, E. Rybin, D. Petrie, J.R. Travers, M.E. Bouatia-Naji, N. Dimas, A.S. Nica, A.C. Wheeler, E. Chen, H. Voight, B.F. Taneera, J. Kanoni, S. Peden, J.F. Turrini, F. Gustafsson, S. Zabena, C. Almgren, P. Barker, D.J.P. Barnes, D. Dennison, E.M. Eriksson, J.G. Eriksson, P. Eury, E. Folkersen, L. Fox, C.S. Frayling, T.M. Goel, A. Gu, H.F. Horikoshi, M. Isomaa, B. Jackson, A.U. Jameson, K.A. Kajantie, E. Kerr-Conte, J. Kuulasmaa, T. Kuusisto, J. Loos, R.J.F. Luan, J. Makrilakis, K. Manning, A.K. Martínez-Larrad, M.T. Narisu, N. Mannila, M.N. Öhrvik, J. Osmond, C. Pascoe, L. Payne, F. Sayer, A.A. Sennblad, B. Silveira, A. Stančcáková, A. Stirrups, K. Swift, A.J. Syvänen, A.-C. Tuomi, T. Van't Hooft, F.M. Walker, M. Weedon, M.N. Xie, W. Zethelius, B. Scott, L.J. Steinthorsdottir, V. Morris, A.P. Dina, C. Welch, R.P. Zeggini, E. Huth, C. Aulchenko, Y.S. Thorleifsson, G. Mcculloch, L.J. Ferreira, T. Grallert, H. Amin, N. Wu, G. Willer, C.J. Raychaudhuri, S. McCarroll, S.A. Hofmann, O.M. Qi, L. Segre, A.V. Van Hoek, M. Navarro, P. Ardlie, K. Balkau, B. Benediktsson, R. Bennett, A.J. Blagieva, R. Boerwinkle, E. Bonnycastle, L.L. Bostrom, K.B. Bravenboer, B. Bumpstead, S. Burtt, N.P. Charpentier, G. Chines, P.S. Cornelis, M. Couper, D.J. Crawford, G. Doney, A.S.F. Elliott, K.S. Elliott, A.L. Erdos, M.R. Franklin, C.S. Ganser, M. Gieger, C. Grarup, N. Green, T. Griffin, S. Groves, C.J. Guiducci, C. Hadjadj, S. Hassanali, N. Herder, C. Johnson, P.R.V. Jorgensen, T. Kao, W.H.L. Klopp, N. Kong, A. Kraft, P. Lauritzen, T. Li, M. Lieverse, A. Lindgren, C.M. Lyssenko, V. Marre, M. Meitinger, T. Midthjell, K. Morken, M.A. Nilsson, P. Owen, K.R. Perry, J.R.B. Petersen, A.-K. Platou, C. Proenca, C. Rathmann, W. Rayner, N.W. Robertson, N.R. Rocheleau, G. Roden, M. Sampson, M.J. Saxena, R. Shields, B.M. Shrader, P. Sigurdsson, G. Sparso, T. Strassburger, K. Stringham, H.M. Sun, Q. Thorand, B. Tichet, J. Van Dam, R.M. Van Haeften, T.W. Van Herpt, T. Van Vliet-Ostaptchouk, J.V. Walters, G.B. Wijmenga, C. Witteman, J.C.M. Bergman, R.N. Cauchi, S. Collins, F.S. Gloyn, A.L. Gyllensten, U. Hansen, T. Hide, W.A. Hitman, G.A. Hofman, A. Hunter, D.J. Hveem, K. Laakso, M. Mohlke, K.L. Morris, A.D. Palmer, C.N.A. Pramstaller, P.P. Rudan, I. Sijbrands, E. Stein, L.D. Tuomilehto, J. Uitterlinden, A.G. Wareham, N.J. Watanabe, R.M. Abecasis, G.R. Boehm, B.O. Campbell, H. Daly, M.J. Hattersley, A.T. Hu, F.B. Meigs, J.B. Pankow, J.S. Pedersen, O. Wichmann, H.-E. Barroso, I. Groop, L. Sladek, R. Thorsteinsdottir, U. Wilson, J.F. Illig, T. Froguel, P. Van Duijn, C.M. Stefansson, K. Altshuler, D. Boehnke, M. McCarthy, M.I. Speliotes, E.K. Berndt, S.I. Monda, K.L. Allen, H.L. Magi, R. Randall, J.C. Vedantam, S. Winkler, T.W. Workalemahu, T. Heid, I.M. Wood, A.R. Weyant, R.J. Estrada, K. Liang, L. Nemesh, J. Park, J.-H. Kilpelainen, T.O. Yang, J. Esko, T. Feitosa, M.F. Kutalik, Z. Mangino, M. Scherag, A. Smith, A.V. Zhao, J.H. Aben, K.K. Absher, D.M. Dixon, A.L. Fisher, E. Glazer, N.L. Goddard, M.E. Heard-Costa, N.L. Hoesel, V. Hottenga, J.-J. Johansson, A. Johnson, T. Ketkar, S. Lamina, C. Li, S. Moffatt, M.F. Myers, R.H. Peters, M.J. Preuss, M. Ripatti, S. Rivadeneira, F. Sandholt, C. Timpson, N.J. Tyrer, J.P. Van Wingerden, S. White, C.C. Wiklund, F. Barlassina, C. Chasman, D.I. Cooper, M.N. Jansson, J.-O. Lawrence, R.W. Pellikka, N. Shi, J. Thiering, E. Alavere, H. Alibrandi, M.T.S. Arnold, A.M. Aspelund, T. Atwood, L.D. Balmforth, A.J. Ben-Shlomo, Y. Bergmann, S. Biebermann, H. Blakemore, A.I.F. Boes, T. Bornstein, S.R. Brown, M.J. Buchanan, T.A. Busonero, F. Cappuccio, F.P. Cavalcanti-Proenca, C. Chen, Y.-D.I. Chen, C.-M. Clarke, R. Coin, L. Connell, J. Day, I.N.M. Den Heijer, M. Duan, J. Ebrahim, S. Elliott, P. Elosua, R. Eiriksdottir, 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.C. Gjesing, A.P. Goyette, P. Grasler, J. Greenawalt, D.M. Gudnason, V. Hartikainen, A.-L. Hall, A.S. Havulinna, A.S. Hayward, C. Heath, A.C. Hengstenberg, C. Hicks, A.A. Hinney, A. Homuth, G. Hui, J. Igl, W. Iribarren, C. Jacobs, K.B. Jarick, I. Jewell, E. John, U. Jousilahti, P. Jula, A. Kaakinen, M. Kaplan, L.M. Kathiresan, S. Kettunen, J. Kinnunen, L. Knowles, J.W. Kolcic, I. König, I.R. Koskinen, S. Kovacs, P. Kvaloy, K. Laitinen, J. Lantieri, O. Lanzani, C. Launer, L.J. Lecoeur, C. Lehtimaki, T. Lettre, G. Liu, J. Lokki, M.-L. Lorentzon, M. Luben, R.N. Ludwig, B. Manunta, P. Marek, D. Martin, N.G. McArdle, W.L. McCarthy, A. McKnight, B. Melander, O. Meyre, D. Montgomery, G.W. 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. Pare, G. Parker, A.N. Perola, M. Pichler, I. Pietilainen, K.H. Platou, C.G.P. Polasek, O. Pouta, A. Rafelt, S. Raitakari, O. Rayner, N.W. Ridderstrale, M. Rief, W. Ruokonen, A. 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. Tammesoo, M.-L. Tardif, J.-C. Teder-Laving, M. Teslovich, T.M. Thompson, J.R. Thomson, B. Tonjes, A. Van Meurs, J.B.J. Van Ommen, G.-J. Vatin, V. Viikari, J. Visvikis-Siest, S. Vitart, V. Vogel, C.I.G. Waite, L.L. Wallaschofski, H. Widen, E. Wiegand, S. Wild, S.H. Willemsen, G. Witte, D.R. Xu, J. Zhang, Q. Zgaga, L. Ziegler, A. Zitting, P. Beilby, J.P. Farooqi, I.S. Hebebrand, J. Huikuri, H.V. James, A.L. Kahonen, M. Levinson, D.F. Macciardi, F. Nieminen, M.S. Ohlsson, C. Palmer, L.J. Ridker, P.M. Stumvoll, M. Beckmann, J.S. Boeing, H. Boomsma, D.I. Caulfield, M.J. Chanock, S.J. Cupples, L.A. Smith, G.D. Erdmann, J. Gronberg, H. Hall, P. Harris, T.B. Hayes, R.B. Heinrich, J. Jarvelin, M.-R. Kaprio, J. Karpe, F. Khaw, K.-T. Kiemeney, L.A. Krude, H. Lawlor, D.A. Metspalu, A. Munroe, P.B. Ouwehand, W.H. Penninx, B.W. Peters, A. Quertermous, T. Reinehr, T. Rissanen, A. Samani, N.J. Schwarz, P.E.H. Shuldiner, A.R. Spector, T.D. Uda, M. Valle, T.T. Wabitsch, M. Waeber, G. Watkins, H. Wright, A.F. Zillikens, M.C. Chatterjee, N. Purcell, S. Schadt, E.E. Visscher, P.M. Assimes, T.L. Borecki, I.B. Deloukas, P. Haritunians, T. Kaplan, R.C. O'Connell, J.R. Peltonen, L. Schlessinger, D. Strachan, D.P. North, K.E. Hirschhorn, J.N. Ingelsson, E. Parts, L. Glass, D. Nisbet, J. Barrett, A. Sekowska, M. Potter, S. Grundberg, E. Small, K. Hedman, A.K. Bataille, V. Bell, J.T. Surdulescu, G. Ingle, C. Nestle, F.O. Di Meglio, P. Min, J.L. Wilk, A. Hammond, C.J. Yang, T.-P. Montgomery, S.B. Zondervan, K.T. Durbin, R. Ahmadi, K. Dermitzakis, E.T. Reilly, M.P. Holm, H. Stewart, A.F.R. Barbalic, M. Aherrahrou, Z. Allayee, H. Anand, S.S. Andersen, K. Anderson, J.L. Ardissino, D. Ball, S.G. Barnes, T.A. Becker, D.M. Becker, L.C. Berger, K. Bis, J.C. Boekholdt, S.M. Braund, P.S. Burnett, M.S. Buysschaert, I. Carlquist, J.F. Chen, L. Codd, V. Davies, R.W. Cichon, S. Dedoussis, G.V. Demissie, S. Dehghan, A. Devaney, J.M. Diemert, P. Do, R. Doering, A. Eifert, S. El Mokhtari, N.E. Ellis, S.G. Engert, J.C. Epstein, S.E. De Faire, U. Fischer, M. Freyer, J. Gigante, B. Girelli, D. Gretarsdottir, S. Gulcher, J.R. Halperin, E. Hammond, N. Hazen, S.L. Horne, B.D. Jones, G.T. Jukema, J.W. Kaiser, M.A. Kastelein, J.J.P. Kolovou, G. Laaksonen, R. Lambrechts, D. Leander, K. Li, M. Lieb, W. Loley, C. Lotery, A.J. Mannucci, P.M. Maouche, S. Martinelli, N. McKeown, P.P. Meisinger, C. Merlini, P.A. Mooser, V. Morgan, T. Mühleisen, T.W. Muhlestein, J.B. Münzel, T. Musunuru, K. Nahrstaedt, J. Nelson, C.P. Nöthen, M.M. Olivieri, O. Patel, R.S. Patterson, C.C. Peyvandi, F. Qu, L. Quyyumi, A.A. Rader, D.J. Rallidis, L.S. Rice, C. Rosendaal, F.R. Rubin, D. Sampietro, M.L. Sandhu, M.S. Schadt, E. Schäfer, A. Schillert, A. Schrezenmeir, J. Schwartz, S.M. Sivananthan, M. Sivapalaratnam, S. Smith, T.B. Snoep, J.D. Spertus, J.A. Stark, K. Stoll, M. Wilson Tang, W.H. Tennstedt, S. Thorgeirsson, G. Tomaszewski, M. Van Rij, A.M. Wells, G.A. Wild, P.S. Willenborg, C. Wright, B.J. Ye, S. Zeller, T. Cambien, F. Goodall, A.H. Marz, W. Blankenberg, S. Roberts, R. McPherson, R. Hopewell, J.C. Parish, S. Offer, A. Bowman, L. Sleight, P. Armitage, J. Peto, R. Collins, R. Chambers, J.C. Ahmed, N. Donnelly, P. Kooner, A.S. Scott, J. Sehmi, J. Zhang, W. Kooner, J. Sabater-Lleal, M. Mälarstig, A. Hellénius, M.-L. Olsson, G. Rust, S. Assmann, G. Seedorf, U. Barlera, S. Tognoni, G. Franzosi, M.G. Linksted, P. Ongen, H. Kyriakou, T. Green, F. Farrall, M. Saleheen, D. Rasheed, A. Zaidi, M. Shah, N. Samuel, M. Mallick, N. Azhar, M. Zaman, K. Samad, A. Ishaq, M. Gardezi, A. Memon, F.-U.-R. Frossard, P. Danesh, J. Östenson, C.-G. Lind, L. Cooper, C.C. Serrano-Ríos, M. Ferrannini, E. Forsen, T.J. Pattou, F. Langenberg, C. Hamsten, A. Florez, J.C.
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endocrine system ,endocrine system diseases ,nutritional and metabolic diseases - Abstract
OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10-8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/ C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 3 10-4), improved b-cell function (P = 1.1 × 10-5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10-6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS - We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis. © 2011 by the American Diabetes Association.
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- 2011
13. Addressing Genomic Imprinting in a Family-based Genome-wide Association Study
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Scherag, Andre, Jarick, I., Pütter, Carolin, Hinney, Anke, Horsthemke, Bernhard, Jöckel, Karl-Heinz, and Hebebrand, Johannes
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Medizin - Published
- 2010
14. The performance of conditional tests in associated regions derived from genome-wide association studies
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Greene, B, Jarick, I, Hinney, A, Hebebrand, J, and Schäfer, H
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Genome-wide association studies (GWAS) have been used successfully to identify genetic loci associated with complex diseases and phenotypes. So far this association often takes the form of several significant signals (such as small p-values) in a univariate analysis at various markers within a single[for full text, please go to the a.m. URL], 54. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds)
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- 2009
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15. Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder
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Jarick, I., Volckmar, A-L, Puetter, C., Pechlivanis, S., Nguyen, T. T., Dauvermann, M. R., Beck, S., Albayrak, Oe, Scherag, S., Gilsbach, S., Cichon, S., Hoffmann, P., Degenhardt, F., Noethen, M. M., Schreiber, S., Wichmann, H-E, Joeckel, K-H, Heinrich, J., Tiesler, C. M. T., Faraone, S. V., Walitza, S., Sinzig, J., Freitag, C., Meyer, J., Herpertz-Dahlmann, B., Lehmkuhl, G., Renner, T. J., Warnke, A., Romanos, M., Lesch, K-P, Reif, A., Schimmelmann, B. G., Hebebrand, J., Scherag, A., Hinney, A., Jarick, I., Volckmar, A-L, Puetter, C., Pechlivanis, S., Nguyen, T. T., Dauvermann, M. R., Beck, S., Albayrak, Oe, Scherag, S., Gilsbach, S., Cichon, S., Hoffmann, P., Degenhardt, F., Noethen, M. M., Schreiber, S., Wichmann, H-E, Joeckel, K-H, Heinrich, J., Tiesler, C. M. T., Faraone, S. V., Walitza, S., Sinzig, J., Freitag, C., Meyer, J., Herpertz-Dahlmann, B., Lehmkuhl, G., Renner, T. J., Warnke, A., Romanos, M., Lesch, K-P, Reif, A., Schimmelmann, B. G., Hebebrand, J., Scherag, A., and Hinney, A.
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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 (> 500kb) 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 x 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 x 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 x 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.
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- 2014
16. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- Author
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Berndt, S.I., Gustafsson, S., Magi, 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., Ferreira, T., Gentilini, D., Jackson, A.U., Luan, J., Randall, J.C., Vedantam, S., Willer, C.J., Winkler, T.W., Wood, A.R., Workalemahu, T., Hu, Y.J., Lee, S., Liang, L., Lin, D.Y., Min, J.L., Neale, B.M., Thorleifsson, G., Yang, J., Albrecht, E., Amin, N., Bragg-Gresham, J.L., Cadby, G., Heijer, M. den, Eklund, N., Fischer, K., Goel, A., Hottenga, J.J., Huffman, J.E., Jarick, I., Johansson, A, Johnson, T., Kanoni, S., Kleber, M.E., Konig, I.R., Kristiansson, K., Kutalik, Z., Lamina, C., Lecoeur, C., Li, G., Mangino, M., McArdle, W.L., Medina-Gomez, C., Muller-Nurasyid, M., Ngwa, J.S., Nolte, I.M., Paternoster, L., Pechlivanis, S., Perola, M., Peters, M.J., Preuss, M., Rose, L.M., Shi, J., Shungin, D., Smith, A.V., Strawbridge, R.J., Surakka, I., Teumer, A., Trip, M.D., Tyrer, J., Vliet-Ostaptchouk, J.V. Van, 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., Bonnycastle, L.L., Brambilla, P., Bruinenberg, M., Campbell, H., Chasman, D.I., Chines, P.S., Collins, F.S., Connell, J.M., Cookson, W.O., Faire, U. de, Vegt, F. de, Dei, M., Dimitriou, M., Edkins, S., Estrada, K., Evans, D.M., Farrall, M., Ferrario, M.M., Vermeulen, S., Kiemeney, L.A.L.M., et al., Berndt, S.I., Gustafsson, S., Magi, 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., Ferreira, T., Gentilini, D., Jackson, A.U., Luan, J., Randall, J.C., Vedantam, S., Willer, C.J., Winkler, T.W., Wood, A.R., Workalemahu, T., Hu, Y.J., Lee, S., Liang, L., Lin, D.Y., Min, J.L., Neale, B.M., Thorleifsson, G., Yang, J., Albrecht, E., Amin, N., Bragg-Gresham, J.L., Cadby, G., Heijer, M. den, Eklund, N., Fischer, K., Goel, A., Hottenga, J.J., Huffman, J.E., Jarick, I., Johansson, A, Johnson, T., Kanoni, S., Kleber, M.E., Konig, I.R., Kristiansson, K., Kutalik, Z., Lamina, C., Lecoeur, C., Li, G., Mangino, M., McArdle, W.L., Medina-Gomez, C., Muller-Nurasyid, M., Ngwa, J.S., Nolte, I.M., Paternoster, L., Pechlivanis, S., Perola, M., Peters, M.J., Preuss, M., Rose, L.M., Shi, J., Shungin, D., Smith, A.V., Strawbridge, R.J., Surakka, I., Teumer, A., Trip, M.D., Tyrer, J., Vliet-Ostaptchouk, J.V. Van, 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., Bonnycastle, L.L., Brambilla, P., Bruinenberg, M., Campbell, H., Chasman, D.I., Chines, P.S., Collins, F.S., Connell, J.M., Cookson, W.O., Faire, U. de, Vegt, F. de, Dei, M., Dimitriou, M., Edkins, S., Estrada, K., Evans, D.M., Farrall, M., Ferrario, M.M., Vermeulen, S., Kiemeney, L.A.L.M., and et al.
- Abstract
Item does not contain fulltext, Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
- Published
- 2013
17. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- Author
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Berndt, S.I. (Sonja), Gustafsson, S. (Stefan), Mägi, R. (Reedik), Ganna, A. (Andrea), Wheeler, E. (Eleanor), Feitosa, M.F. (Mary Furlan), Justice, A.E. (Anne), Monda, K.L. (Keri), Croteau-Chonka, D.C. (Damien), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Ferreira, T. (Teresa), Gentilini, D. (Davide), Jackson, A.U. (Anne), Luan, J., Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Willer, C.J. (Cristen), Winkler, T.W. (Thomas), Wood, A.R. (Andrew), Workalemahu, T. (Tsegaselassie), Hu, Y.-J. (Yi-Juan), Lee, S.H. (Sang Hong), Liang, L. (Liming), Lin, D.Y. (Dan), Min, J. (Josine), Neale, B.M. (Benjamin), Thorleifsson, G. (Gudmar), Yang, J. (Jian), Albrecht, E. (Eva), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Heijer, M. (Martin) den, Eklund, N. (Niina), Fischer, K. (Krista), Goel, A. (Anuj), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jarick, I. (Ivonne), Johansson, A. (Åsa), Johnson, T. (Toby), Kanoni, S. (Stavroula), Kleber, M.E. (Marcus), König, I.R. (Inke), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lamina, C. (Claudia), Lecoeur, C. (Cécile), Li, G. (Guo), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Medina-Gomez, M.C. (Carolina), Müller-Nurasyid, M. (Martina), Ngwa, J.S., Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Pechlivanis, S. (Sonali), Perola, M. (Markus), Peters, M.J. (Marjolein), Preuss, M. (Michael), Rose, L.M. (Lynda), Shi, J. (Jianxin), Shungin, D. (Dmitry), Smith, A.V. (Davey), Strawbridge, R.J. (Rona), Surakka, I. (Ida), Teumer, A. (Alexander), Trip, M.D. (Mieke), Tyrer, J.P. (Jonathan), Vliet-Ostaptchouk, J.V. (Jana) van, Vandenput, L. (Liesbeth), Waite, L. (Lindsay), Zhao, J.H. (Jing Hua), Absher, D. (Devin), Asselbergs, F.W. (Folkert), Atalay, M. (Mustafa), Attwood, A.P. (Antony), Balmforth, A.J. (Anthony), Basart, D.C.G. (Dick), Beilby, J.P. (John), Bonnycastle, L.L. (Lori), Brambilla, P. (Paolo), Bruinenberg, M. (M.), Campbell, H. (Harry), Chasman, D.I. (Daniel), Chines, P.S. (Peter), Collins, F.S. (Francis), Connell, J. (John), Cookson, W.O. (William), Faire, U. (Ulf) de, Vegt, F. (Femmie) de, Dei, M. (Mariano), Dimitriou, M. (Maria), Edkins, T. (Ted), Estrada Gil, K. (Karol), Evans, D.M. (David), Farrall, M. (Martin), Ferrario, F. (Franco), Ferrières, J. (Jean), Franke, L. (Lude), Frau, F. (Francesca), Gejman, P.V. (Pablo), Grallert, H. (Harald), Grönberg, H. (Henrik), Gudnason, V. (Vilmundur), Hall, A. (Anne), Hall, A.S. (Alistair), Hartikainen, A.L., Hayward, C. (Caroline), Heard-Costa, N.L. (Nancy), Heath, A.C. (Andrew), Hebebrand, J. (Johannes), Homuth, G. (Georg), Hu, F.B. (Frank), Hunt, S.E. (Sarah), Hyppönen, E. (Elina), Iribarren, C. (Carlos), Jacobs, K.B. (Kevin), Jansson, J.-O. (John-Olov), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Kee, F. (F.), Khaw, K-T. (Kay-Tee), Kivimaki, M. (Mika), Koenig, W. (Wolfgang), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lind, L. (Lars), Lindstrom, J. (Jaana), Liu, J. (Jianjun), Liuzzi, A. (Antonio), Lokki, M.L., Lorentzon, M. (Mattias), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Manunta, P. (Paolo), Marek, D. (Diana), März, W. (Winfried), Leach, I.M. (Irene Mateo), McKnight, B. (Barbara), Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milani, L. (Lili), Montgomery, G.W. (Grant), Mooser, V. (Vincent), Mühleisen, T.W. (Thomas), Munroe, P. (Patricia), Musk, A.W. (Arthur), Narisu, N. (Narisu), Navis, G. (Gerjan), Nicholson, G. (Ggeorge), Nohr, C. (Christian), Ong, K. (Ken), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Palotie, A. (Aarno), Peden, J. (John), Pedersen, N.L. (Nancy), Peters, A. (Annette), Polasek, O. (Ozren), Pouta, A. (Anneli), Pramstaller, P.P. (Peter Paul), Prokopenko, I. (Inga), Pütter, C. (Carolin), Radhakrishnan, A. (Aparna), Raitakari, O. (Olli), Rendon, A. (Augusto), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Saaristo, T. (Timo), Sambrook, J.G. (Jennifer), Sanders, A.R. (Alan), Sanna, S. (Serena), Saramies, J. (Jouko), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Shin, S.-Y., Signorini, S. (Stefano), Sinisalo, J. (Juha), Skrobek, B. (Boris), Soranzo, N. (Nicole), Stancáková, A. (Alena), Stark, K. (Klaus), Stephens, J. (Jonathan), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Stumvoll, M. (Michael), Swift, A.J. (Amy), Theodoraki, E.V. (Eirini), Thorand, B. (Barbara), Tregouet, D.-A. (David-Alexandre), Tremoli, E. (Elena), Klauw, M.M. (Melanie) van der, Meurs, J.B.J. (Joyce) van, Vermeulen, S.H.H.M. (Sita), Viikari, J. (Jorma), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Waeber, G. (Gérard), Wang, Z. (Zhaoming), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Winkelmann, B., Witteman, J.C.M. (Jacqueline), Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Amouyel, P. (Philippe), Boehm, B.O. (Bernhard), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Cupples, L.A. (Adrienne), Cusi, D. (Daniele), Dedoussis, G.V. (George), Erdmann, J. (Jeanette), Eriksson, J.G. (Johan), Franks, P.W. (Paul), Froguel, P. (Philippe), Gieger, C. (Christian), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hinney, A. (Anke), Hofman, A. (Albert), Hovingh, G.K. (Kees), Hveem, K. (Kristian), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Jöckel, K.-H. (Karl-Heinz), Keinanen-Kiukaanniemi, S. (Sirkka), Kiemeney, L.A.L.M. (Bart), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Levinson, D.F. (Douglas), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Morris, A.D. (Andrew), Nieminen, M.S. (Markku), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ouwehand, W.H. (Willem), Palmer, C. (Cameron), Penninx, B.W.J.H. (Brenda), Power, C. (Christopher), Province, M.A. (Mike), Psaty, B.M. (Bruce), Qi, L. (Lu), Rauramaa, R. (Rainer), Ridker, P.M. (Paul), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Snieder, H. (Harold), Sorensen, H.G., Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Tönjes, A. (Anke), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Vollenweider, P. (Peter), Wallaschofski, H. (Henri), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Wilson, J.F. (James F), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C. (Craig), Frayling, T.M. (Timothy), Groop, L. (Leif), Haritunian, T. (Talin), Heid, I.M. (Iris), Hunter, D. (David), Kaplan, R.C. (Robert), Karpe, F. (Fredrik), Moffatt, M.F. (Miriam), Mohlke, K.L. (Karen), O´Connell, J.R., Pawitan, Y. (Yudi), Schadt, E.E. (Eric), Schlessinger, D. (David), Steinthorsdottir, V. (Valgerdur), Strachan, D.P. (David), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Di Blasio, A.M. (Anna Maria), Hirschhorn, J.N. (Joel), Lindgren, C.M. (Cecilia), Meyre, D. (David), Scherag, A. (Andre), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Loos, R.J.F. (Ruth), Ingelsson, E. (Erik), Berndt, S.I. (Sonja), Gustafsson, S. (Stefan), Mägi, R. (Reedik), Ganna, A. (Andrea), Wheeler, E. (Eleanor), Feitosa, M.F. (Mary Furlan), Justice, A.E. (Anne), Monda, K.L. (Keri), Croteau-Chonka, D.C. (Damien), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Ferreira, T. (Teresa), Gentilini, D. (Davide), Jackson, A.U. (Anne), Luan, J., Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Willer, C.J. (Cristen), Winkler, T.W. (Thomas), Wood, A.R. (Andrew), Workalemahu, T. (Tsegaselassie), Hu, Y.-J. (Yi-Juan), Lee, S.H. (Sang Hong), Liang, L. (Liming), Lin, D.Y. (Dan), Min, J. (Josine), Neale, B.M. (Benjamin), Thorleifsson, G. (Gudmar), Yang, J. (Jian), Albrecht, E. (Eva), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Heijer, M. (Martin) den, Eklund, N. (Niina), Fischer, K. (Krista), Goel, A. (Anuj), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jarick, I. (Ivonne), Johansson, A. (Åsa), Johnson, T. (Toby), Kanoni, S. (Stavroula), Kleber, M.E. (Marcus), König, I.R. (Inke), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lamina, C. (Claudia), Lecoeur, C. (Cécile), Li, G. (Guo), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Medina-Gomez, M.C. (Carolina), Müller-Nurasyid, M. (Martina), Ngwa, J.S., Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Pechlivanis, S. (Sonali), Perola, M. (Markus), Peters, M.J. (Marjolein), Preuss, M. (Michael), Rose, L.M. (Lynda), Shi, J. (Jianxin), Shungin, D. (Dmitry), Smith, A.V. (Davey), Strawbridge, R.J. (Rona), Surakka, I. (Ida), Teumer, A. (Alexander), Trip, M.D. (Mieke), Tyrer, J.P. (Jonathan), Vliet-Ostaptchouk, J.V. (Jana) van, Vandenput, L. (Liesbeth), Waite, L. (Lindsay), Zhao, J.H. (Jing Hua), Absher, D. (Devin), Asselbergs, F.W. (Folkert), Atalay, M. (Mustafa), Attwood, A.P. (Antony), Balmforth, A.J. (Anthony), Basart, D.C.G. (Dick), Beilby, J.P. (John), Bonnycastle, L.L. (Lori), Brambilla, P. (Paolo), Bruinenberg, M. (M.), Campbell, H. (Harry), Chasman, D.I. (Daniel), Chines, P.S. (Peter), Collins, F.S. (Francis), Connell, J. (John), Cookson, W.O. (William), Faire, U. (Ulf) de, Vegt, F. (Femmie) de, Dei, M. (Mariano), Dimitriou, M. (Maria), Edkins, T. (Ted), Estrada Gil, K. (Karol), Evans, D.M. (David), Farrall, M. (Martin), Ferrario, F. (Franco), Ferrières, J. (Jean), Franke, L. (Lude), Frau, F. (Francesca), Gejman, P.V. (Pablo), Grallert, H. (Harald), Grönberg, H. (Henrik), Gudnason, V. (Vilmundur), Hall, A. (Anne), Hall, A.S. (Alistair), Hartikainen, A.L., Hayward, C. (Caroline), Heard-Costa, N.L. (Nancy), Heath, A.C. (Andrew), Hebebrand, J. (Johannes), Homuth, G. (Georg), Hu, F.B. (Frank), Hunt, S.E. (Sarah), Hyppönen, E. (Elina), Iribarren, C. (Carlos), Jacobs, K.B. (Kevin), Jansson, J.-O. (John-Olov), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Kee, F. (F.), Khaw, K-T. (Kay-Tee), Kivimaki, M. (Mika), Koenig, W. (Wolfgang), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lind, L. (Lars), Lindstrom, J. (Jaana), Liu, J. (Jianjun), Liuzzi, A. (Antonio), Lokki, M.L., Lorentzon, M. (Mattias), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Manunta, P. (Paolo), Marek, D. (Diana), März, W. (Winfried), Leach, I.M. (Irene Mateo), McKnight, B. (Barbara), Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milani, L. (Lili), Montgomery, G.W. (Grant), Mooser, V. (Vincent), Mühleisen, T.W. (Thomas), Munroe, P. (Patricia), Musk, A.W. (Arthur), Narisu, N. (Narisu), Navis, G. (Gerjan), Nicholson, G. (Ggeorge), Nohr, C. (Christian), Ong, K. (Ken), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Palotie, A. (Aarno), Peden, J. (John), Pedersen, N.L. (Nancy), Peters, A. (Annette), Polasek, O. (Ozren), Pouta, A. (Anneli), Pramstaller, P.P. (Peter Paul), Prokopenko, I. (Inga), Pütter, C. (Carolin), Radhakrishnan, A. (Aparna), Raitakari, O. (Olli), Rendon, A. (Augusto), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Saaristo, T. (Timo), Sambrook, J.G. (Jennifer), Sanders, A.R. (Alan), Sanna, S. (Serena), Saramies, J. (Jouko), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Shin, S.-Y., Signorini, S. (Stefano), Sinisalo, J. (Juha), Skrobek, B. (Boris), Soranzo, N. (Nicole), Stancáková, A. (Alena), Stark, K. (Klaus), Stephens, J. (Jonathan), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Stumvoll, M. (Michael), Swift, A.J. (Amy), Theodoraki, E.V. (Eirini), Thorand, B. (Barbara), Tregouet, D.-A. (David-Alexandre), Tremoli, E. (Elena), Klauw, M.M. (Melanie) van der, Meurs, J.B.J. (Joyce) van, Vermeulen, S.H.H.M. (Sita), Viikari, J. (Jorma), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Waeber, G. (Gérard), Wang, Z. (Zhaoming), Widen, E. (Elisabeth), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Winkelmann, B., Witteman, J.C.M. (Jacqueline), Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Amouyel, P. (Philippe), Boehm, B.O. (Bernhard), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Cupples, L.A. (Adrienne), Cusi, D. (Daniele), Dedoussis, G.V. (George), Erdmann, J. (Jeanette), Eriksson, J.G. (Johan), Franks, P.W. (Paul), Froguel, P. (Philippe), Gieger, C. (Christian), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hinney, A. (Anke), Hofman, A. (Albert), Hovingh, G.K. (Kees), Hveem, K. (Kristian), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Jöckel, K.-H. (Karl-Heinz), Keinanen-Kiukaanniemi, S. (Sirkka), Kiemeney, L.A.L.M. (Bart), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Levinson, D.F. (Douglas), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Morris, A.D. (Andrew), Nieminen, M.S. (Markku), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ouwehand, W.H. (Willem), Palmer, C. (Cameron), Penninx, B.W.J.H. (Brenda), Power, C. (Christopher), Province, M.A. (Mike), Psaty, B.M. (Bruce), Qi, L. (Lu), Rauramaa, R. (Rainer), Ridker, P.M. (Paul), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Snieder, H. (Harold), Sorensen, H.G., Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Tönjes, A. (Anke), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Vollenweider, P. (Peter), Wallaschofski, H. (Henri), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Wilson, J.F. (James F), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C. (Craig), Frayling, T.M. (Timothy), Groop, L. (Leif), Haritunian, T. (Talin), Heid, I.M. (Iris), Hunter, D. (David), Kaplan, R.C. (Robert), Karpe, F. (Fredrik), Moffatt, M.F. (Miriam), Mohlke, K.L. (Karen), O´Connell, J.R., Pawitan, Y. (Yudi), Schadt, E.E. (Eric), Schlessinger, D. (David), Steinthorsdottir, V. (Valgerdur), Strachan, D.P. (David), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Di Blasio, A.M. (Anna Maria), Hirschhorn, J.N. (Joel), Lindgren, C.M. (Cecilia), Meyre, D. (David), Scherag, A. (Andre), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Loos, R.J.F. (Ruth), and Ingelsson, E. (Erik)
- Abstract
Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
- Published
- 2013
- Full Text
- View/download PDF
18. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- Author
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Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Berndt, SI, Feitosa, MF, Justice, AE, Monda, KL, Croteau Chonka, DC, Day, FR, Jackson, AU, Randall, JC, Willer, CJ, Winkler, TW, Wood, AR, Hu, YJ, Lee, SH, Lin, DY, Min, JL, Neale, BM, Bragg Gresham, JL, Hottenga, JJ, Huffman, JE, Kleber, ME, König, IR, McArdle, WL, Ngwa, JS, Nolte, IM, Peters, MJ, Rose, LM, Smith, AV, Strawbridge, RJ, Trip, MD, Van Vliet Ostaptchouk, JV, Waite, LL, Zhao, JH, Asselbergs, FW, Attwood, AP, Balmforth, AJ, Bonnycastle, LL, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de, Faire, U, de, Evans, DM, Ferrario, MM, Gejman, PV, Hall, AS, Hartikainen, AL, Heard Costa, NL, Heath, AC, Hu, FB, Hunt, SE, Jacobs, KB, Jansson, JO, Khaw, KT, Kraja, AT, Laitinen, JH, Lakka, TA, Launer, LJ, Lokki, ML, Madden, PA, Magnusson, PK, McKnight, B, Medland, SE, Montgomery, GW, Mühleisen, TW, Munroe, PB, Musk, AW, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CN, Peden, JF, Pramstaller, PP, Saaristo, TE, Sambrook, JG, Sanders, AR, Shin, SY, Stephens, JC, Stolk, RP, Swift, AJ, Theodoraki, EV, Tregouet, DA, Van der Klauw, MM, van Meurs, JB, Vermeulen, SH, Wild, SH, Winkelmann, BR, Witteman, JC, Wolffenbuttel, BH, Wright, AF, Zillikens, MC, Boehm, BO, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, LA, Dedoussis, GV, Eriksson, JG, Franks, PW, Harris, TB, Hicks, AA, Hovingh, KG, Jarvelin, MR, Jöckel, KH, Keinanen Kiukaanniemi, SM, Kiemeney, LA, Levinson, DF, Martin, NG, Morris, AD, Nieminen, MS, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Province, MA, Psaty, BM, Ridker, PM, Samani, NJ, Sørensen, TI, Spector, TD, Uitterlinden, AG, Wareham, NJ, Wichmann, HE, Wilson, JF, Abecasis, GR, Assimes, TL, Borecki, IB, Fox, CS, Groop, LC, Heid, IM, Kaplan, RC, Moffatt, MF, Mohlke, KL, O'Connell, JR, Schadt, EE, Strachan, DP, van, Duijn, CM, Visscher, PM, Di Blasio, AM, Hirschhorn, JN, Lindgren, CM, Morris, AP, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJ, Ingelsson, E., BRAMBILLA, PAOLO, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Berndt, SI, Feitosa, MF, Justice, AE, Monda, KL, Croteau Chonka, DC, Day, FR, Jackson, AU, Randall, JC, Willer, CJ, Winkler, TW, Wood, AR, Hu, YJ, Lee, SH, Lin, DY, Min, JL, Neale, BM, Bragg Gresham, JL, Hottenga, JJ, Huffman, JE, Kleber, ME, König, IR, McArdle, WL, Ngwa, JS, Nolte, IM, Peters, MJ, Rose, LM, Smith, AV, Strawbridge, RJ, Trip, MD, Van Vliet Ostaptchouk, JV, Waite, LL, Zhao, JH, Asselbergs, FW, Attwood, AP, Balmforth, AJ, Bonnycastle, LL, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de, Faire, U, de, Evans, DM, Ferrario, MM, Gejman, PV, Hall, AS, Hartikainen, AL, Heard Costa, NL, Heath, AC, Hu, FB, Hunt, SE, Jacobs, KB, Jansson, JO, Khaw, KT, Kraja, AT, Laitinen, JH, Lakka, TA, Launer, LJ, Lokki, ML, Madden, PA, Magnusson, PK, McKnight, B, Medland, SE, Montgomery, GW, Mühleisen, TW, Munroe, PB, Musk, AW, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CN, Peden, JF, Pramstaller, PP, Saaristo, TE, Sambrook, JG, Sanders, AR, Shin, SY, Stephens, JC, Stolk, RP, Swift, AJ, Theodoraki, EV, Tregouet, DA, Van der Klauw, MM, van Meurs, JB, Vermeulen, SH, Wild, SH, Winkelmann, BR, Witteman, JC, Wolffenbuttel, BH, Wright, AF, Zillikens, MC, Boehm, BO, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, LA, Dedoussis, GV, Eriksson, JG, Franks, PW, Harris, TB, Hicks, AA, Hovingh, KG, Jarvelin, MR, Jöckel, KH, Keinanen Kiukaanniemi, SM, Kiemeney, LA, Levinson, DF, Martin, NG, Morris, AD, Nieminen, MS, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Province, MA, Psaty, BM, Ridker, PM, Samani, NJ, Sørensen, TI, Spector, TD, Uitterlinden, AG, Wareham, NJ, Wichmann, HE, Wilson, JF, Abecasis, GR, Assimes, TL, Borecki, IB, Fox, CS, Groop, LC, Heid, IM, Kaplan, RC, Moffatt, MF, Mohlke, KL, O'Connell, JR, Schadt, EE, Strachan, DP, van, Duijn, CM, Visscher, PM, Di Blasio, AM, Hirschhorn, JN, Lindgren, CM, Morris, AP, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJ, Ingelsson, E., and BRAMBILLA, PAOLO
- Abstract
Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups
- Published
- 2013
19. Genome-wide association study in German patients with attention deficit/hyperactivity disorder
- Author
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Hinney, A., Scherag, A., Jarick, I., Albayrak, O., Putter, C. de, Pechlivanis, S., Dauvermann, M.R., Beck, S., Weber, H., Scherag, S., Nguyen, T.T., Volckmar, A.L., Knoll, N., Faraone, S.V., Neale, B.M., Franke, B., Cichon, S., Hoffmann, P., Nothen, Markus, Schreiber, S., Jockel, K.H., Wichmann, H.E., Freitag, C., Lempp, T., Meyer, J., Gilsbach, S., Herpertz-Dahlmann, B., Sinzig, J., Lehmkuhl, G., Renner, T.J., Warnke, A., Romanos, M., Lesch, K.P., Reif, A., Schimmelmann, B.G., Hebebrand, J., Hinney, A., Scherag, A., Jarick, I., Albayrak, O., Putter, C. de, Pechlivanis, S., Dauvermann, M.R., Beck, S., Weber, H., Scherag, S., Nguyen, T.T., Volckmar, A.L., Knoll, N., Faraone, S.V., Neale, B.M., Franke, B., Cichon, S., Hoffmann, P., Nothen, Markus, Schreiber, S., Jockel, K.H., Wichmann, H.E., Freitag, C., Lempp, T., Meyer, J., Gilsbach, S., Herpertz-Dahlmann, B., Sinzig, J., Lehmkuhl, G., Renner, T.J., Warnke, A., Romanos, M., Lesch, K.P., Reif, A., Schimmelmann, B.G., and Hebebrand, J.
- Abstract
Item does not contain fulltext, The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome-wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM-IV criteria; Human660W-Quadv1; Illumina, San Diego, CA) and on 1,300 population-based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P-values (best P-value: 8.38 x 10(-7) ) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P-values (P-values = 7.57 x 10(-5) ) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect-size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta-analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect-size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome-wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P-values compared to SNPs within random sets of genes of the same size. We did not find genome-wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD. (c) 2011 Wiley Periodicals, Inc.
- Published
- 2011
20. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- Author
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Speliotes, E.K. (Elizabeth), Willer, C.J. (Cristen), Berndt, S.I. (Sonja), Monda, K.L. (Keri), Thorleifsson, G. (Gudmar), Jackson, A.U. (Anne), Allen, H.L., Lindgren, C.M. (Cecilia), Luan, J., Mägi, R. (Reedik), Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Winkler, T.W. (Thomas), Qi, L. (Lu), Workalemahu, T. (Tsegaselassie), Heid, I.M. (Iris), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Wheeler, E. (Eleanor), Wood, A.R. (Andrew), Ferreira, T. (Teresa), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Eestrada, K. (Karol), Liang, L. (Liming), Nemesh, J. (James), Park, J.H., Gustafsson, S. (Stefan), Kilpeläinen, T.O. (Tuomas), Yang, J. (Joanna), Bouatia-Naji, N. (Nabila), Eesko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Kutalik, Z. (Zoltán), Mangino, M. (Massimo), Raychaudhuri, S. (Soumya), Scherag, A. (Andre), Smith, A.V. (Albert Vernon), Welch, R.P. (Ryan), Zhao, J.H. (Jing Hua), Aben, K.K.H. (Katja), Absher, D. (Devin), Amin, N. (Najaf), Dixon, A.L. (Anna), Fisher, E. (Eeva), Glazer, N.L. (Nicole), Goddard, M.E. (Michael), Heard-Costa, N.L. (Nancy), Hoesel, V. (Volker), Hottenga, J.J. (Jouke Jan), Johansson, A. (Åsa), Johnson, T. (Toby), Ketkar, S. (Shamika), Lamina, C. (Claudia), Li, S. (Shengxu), Moffatt, M.F. (Miriam), Myers, R.H. (Richard), Narisu, N. (Narisu), Perry, J.R.B. (John), Peters, M.J. (Marjolein), Preuss, M. (Michael), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Sandholt, C. (Camilla), Scott, L.J. (Laura), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Wingerden, S. (Sophie) van, White, C.C. (Charles), Wiklund, F. (Fredrik), Barlassina, C. (Christina), Chasman, D.I. (Daniel), Cooper, M.N. (Matthew), Jansson, J.O., Lawrence, R.W. (Robert), Pellikka, N. (Niina), Prokopenko, I. (Inga), Shi, J. (Jianxin), Thiering, E. (Eelisabeth), Alavere, H. (Helene), Alibrandi, M.T.S. (Maria), Almgren, P. (Peter), Arnold, A.M. (Alice), Aspelund, T. (Thor), Atwood, L.D. (Larry), Balkau, B. (Beverley), Balmforth, A.J. (Anthony), Bennett, A.J. (Amanda), Ben-Shlomo, Y., Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Biebermann, H. (Heike), Blakemore, A.I.F. (Alexandra), Boes, T. (Tanja), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Buchanan, T.A. (Thomas), Busonero, F., Campbell, H. (Harry), Cappuccio, F.P. (Francesco), Cavalcanti-Proença, C. (Christine), Chen, Y.D.I. (Yii-Der Ida), Chen, C.-M. (Chih-Mei), Chines, P.S. (Peter), Clarke, R., Coin, L. (Lachlan), Connell, J. (John), Day, I.N.M. (Ian), Heijer, M. (Martin) den, Duan, J. (Jubao), Eebrahim, S. (Shah), Eelliott, P. (Paul), Eelosua, R. (Roberto), Eeiriksdottir, G. (Gudny), Eerdos, M.R. (Micheal), Eeriksson, J.G. (Johan), Facheris, M.F. (Maurizio), Felix, S.B. (Stephan), Fischer-Posovszky, P. (Pamela), Folsom, A.R. (Aaron), Friedrich, N. (Nele), Freimer, N.B. (Nelson), Fu, M. (Mao), Gaget, S. (Stefan), Gejman, P.V. (Pablo), Geus, E.J.C. (Eco) de, Gieger, C. (Christian), Gjesing, A.P. (Anette), Goel, A. (Anuj), Goyette, P. (Philippe), Grallert, H. (Harald), Gräßler, J. (Jürgen), Greenawalt, D. (Danielle), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Guiducci, C. (Candace), Hartikainen, A.L., Hassanali, N. (Neelam), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Heath, A.C. (Andrew), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hinney, A. (Anke), Hofman, A. (Albert), Homuth, G. (Georg), Hui, J. (Jennie), Igl, W. (Wilmar), Iribarren, C. (Carlos), Isomaa, B. (Bo), Jacobs, K.B. (Kevin), Jarick, I. (Ivonne), Jewell, E. (Eelizabeth), John, U. (Ulrich), Jørgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaakinen, M. (Marika), Kajantie, E. (Eero), Kaplan, R.C. (Robert), Kathiresan, S. (Sekar), Kettunen, J. (Johannes), Kinnunen, L. (Leena), Knowles, J.W. (Joshua), Kolcic, I. (Ivana), König, I.R. (Inke), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kusisto, J. (Johanna), Kraft, P. (Peter), Kvaløy, K. (Kirsti), Laitinen, J. (Jaana), Lantieri, O. (Olivier), Lanzani, C. (Chiara), Launer, L.J. (Lenore), Lecoeur, C. (Cécile), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Liu, J. (Jianjun), Lokki, M.L., Lorentzon, M. (Mattias), Luben, R.N. (Robert), Ludwig, B. (Barbara), Manunta, P. (Paolo), Marek, D. (Diana), Marre, M. (Michel), Martin, N.G. (Nicholas), McArdle, W.L. (Wendy), McCarthy, M.I. (Mark), McKnight, B. (Barbara), Meitinger, T. (Thomas), Melander, O. (Olle), Meyre, D. (David), Midthjell, K. (Kristian), Montgomery, G.W. (Grant), Morken, M.A. (Mario), Morris, A.D. (Andrew), Mulic, R. (Rosanda), Ngwa, J.S., Nelis, M. (Mari), Neville, M.J. (Matthew), Nyholt, D.R. (Dale), O'Ddonnell, C.J. (Christopher), O'Rahilly, S. (Stephen), Ong, K. (Ken), Oostra, B.A. (Ben), Paré, G. (Guillaume), Parker, A.N. (Alex), Perola, M. (Markus), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Platou, C.P. (Carl), Polasek, O. (Ozren), Pouta, A. (Anneli), Rafelt, S. (Suzanne), Raitakari, O. (Olli), Rayner, N.W. (Nigel William), Ridderstråle, M. (Martin), Rief, W. (Winfried), Ruokonen, A. (Aimo), Robertson, N.R. (Neil), Rzehak, P. (Peter), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Saramies, J. (Jouko), Savolainen, M.J. (Markku), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Silander, K. (Kaisa), Sinisalo, J. (Juha), Siscovick, D.S. (David), Smit, J.H. (Jan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Stephens, J. (Jonathan), Surakka, I. (Ida), Swift, A.J. (Amy), Tammesoo, M.L., Tardif, J.-C. (Jean-Claude), Teder-Laving, M. (Maris), Teslovich, T.M. (Tanya), Thompson, J.R. (John), Thomson, B. (Brian), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Meurs, J.B.J. (Joyce) van, OMen, G.J. van, Vatin, V. (Vincent), Viikari, J. (Jorma), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogel, C.I. (Carla), Voight, B.F. (Benjamin), Waite, L. (Lindsay), Wallaschofski, H. (Henri), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wiegand, S. (Susanna), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witte, D.R. (Deniel), Witteman, J.C.M. (Jacqueline), Xu, J. (Jianfeng), Zhang, Q. (Qunyuan), Zgaga, L. (Lina), Ziegler, A. (Andreas), Zitting, P. (Paavo), Beilby, J.P. (John), FarOqi, I.S. (Ssadaf), Hebebrand, J. (Johannes), Huikuri, H.V. (Heikki), James, A. (Alan), Kähönen, M. (Mika), Levinson, D.F. (Douglas), MacCiardi, F. (Fabio), Nieminen, M.S. (Markku), Ohlsson, C. (Claes), Palmer, C. (Cameron), Ridker, P.M. (Paul), Stumvoll, M. (Michael), Beckmann, J.S. (Jacques), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Collins, F.S. (Francis), Cupples, L.A. (Adrienne), Eerdmann, J. (Jeanette), Frogue, P. (Philippe), Grönberg, H. (Henrik), Gyllensten, U. (Ulf), Hansen, T. (Torben), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayes, R.B. (Richard), Heinrich, J. (Joachim), Hu, F.B. (Frank), Hveem, K. (Kristian), Illig, T. (Thomas), Järvelin, M.R., Kaprio, J. (Jaakko), Karpe, F. (Fredrik), Khaw, K-T. (Kay-Tee), Kiemeney, L.A.L.M. (Bart), Krude, H., Laakso, M. (Markku), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Reinehr, T. (Thomas), Rissanen, A. (Aila), Rudan, I. (Igor), Samani, N.J. (Nilesh), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Spector, T.D. (Timothy), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Valle, T.T. (Timo), Wabitsch, M. (Martin), Waeber, G. (Gérard), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Wright, A.F. (Alan), Zillikens, M.C. (Carola), ChatterjE, N. (Nilanjan), McCarroll, S.A. (Steve), Purcell, S. (Shaun), Schadt, E.E. (Eric), Visscher, P.M. (Peter), Assimes, T.L. (Themistocles), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D.J. (David), Mohlke, K.L. (Karen), O'ConneL, J.R. (Jeffrey), Peltonen, L. (Leena Johanna), SchleSinger, D. (David), Strachan, D.P. (David), Watanabe, R.M. (Richard), Duijn, C.M. (Cornelia) van, Wichmann, H.E. (Heinz Erich), Frayling, T.M. (Timothy), Thorsteinsdottir, U. (Unnur), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), StefanSon, K. (Kari), North, K.E. (Kari), McArthy, M.I. (Mark), Hirschhorn, J.N. (Joel), IngelSon, E. (Erik), Loos, R.J.F. (Ruth), Weedon, M.N. (Michael), Speliotes, E.K. (Elizabeth), Willer, C.J. (Cristen), Berndt, S.I. (Sonja), Monda, K.L. (Keri), Thorleifsson, G. (Gudmar), Jackson, A.U. (Anne), Allen, H.L., Lindgren, C.M. (Cecilia), Luan, J., Mägi, R. (Reedik), Randall, J.C. (Joshua), Vedantam, S. (Sailaja), Winkler, T.W. (Thomas), Qi, L. (Lu), Workalemahu, T. (Tsegaselassie), Heid, I.M. (Iris), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Wheeler, E. (Eleanor), Wood, A.R. (Andrew), Ferreira, T. (Teresa), Weyant, R.J. (Robert), Segrè, A.V. (Ayellet), Eestrada, K. (Karol), Liang, L. (Liming), Nemesh, J. (James), Park, J.H., Gustafsson, S. (Stefan), Kilpeläinen, T.O. (Tuomas), Yang, J. (Joanna), Bouatia-Naji, N. (Nabila), Eesko, T. (Tõnu), Feitosa, M.F. (Mary Furlan), Kutalik, Z. (Zoltán), Mangino, M. (Massimo), Raychaudhuri, S. (Soumya), Scherag, A. (Andre), Smith, A.V. (Albert Vernon), Welch, R.P. (Ryan), Zhao, J.H. (Jing Hua), Aben, K.K.H. (Katja), Absher, D. (Devin), Amin, N. (Najaf), Dixon, A.L. (Anna), Fisher, E. (Eeva), Glazer, N.L. (Nicole), Goddard, M.E. (Michael), Heard-Costa, N.L. (Nancy), Hoesel, V. (Volker), Hottenga, J.J. (Jouke Jan), Johansson, A. (Åsa), Johnson, T. (Toby), Ketkar, S. (Shamika), Lamina, C. (Claudia), Li, S. (Shengxu), Moffatt, M.F. (Miriam), Myers, R.H. (Richard), Narisu, N. (Narisu), Perry, J.R.B. (John), Peters, M.J. (Marjolein), Preuss, M. (Michael), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Sandholt, C. (Camilla), Scott, L.J. (Laura), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Wingerden, S. (Sophie) van, White, C.C. (Charles), Wiklund, F. (Fredrik), Barlassina, C. (Christina), Chasman, D.I. (Daniel), Cooper, M.N. (Matthew), Jansson, J.O., Lawrence, R.W. (Robert), Pellikka, N. (Niina), Prokopenko, I. (Inga), Shi, J. (Jianxin), Thiering, E. (Eelisabeth), Alavere, H. (Helene), Alibrandi, M.T.S. (Maria), Almgren, P. (Peter), Arnold, A.M. (Alice), Aspelund, T. (Thor), Atwood, L.D. (Larry), Balkau, B. (Beverley), Balmforth, A.J. (Anthony), Bennett, A.J. (Amanda), Ben-Shlomo, Y., Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Biebermann, H. (Heike), Blakemore, A.I.F. (Alexandra), Boes, T. (Tanja), Bonnycastle, L.L. (Lori), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Buchanan, T.A. (Thomas), Busonero, F., Campbell, H. (Harry), Cappuccio, F.P. (Francesco), Cavalcanti-Proença, C. (Christine), Chen, Y.D.I. (Yii-Der Ida), Chen, C.-M. (Chih-Mei), Chines, P.S. (Peter), Clarke, R., Coin, L. (Lachlan), Connell, J. (John), Day, I.N.M. (Ian), Heijer, M. (Martin) den, Duan, J. (Jubao), Eebrahim, S. (Shah), Eelliott, P. (Paul), Eelosua, R. (Roberto), Eeiriksdottir, G. (Gudny), Eerdos, M.R. (Micheal), Eeriksson, J.G. (Johan), Facheris, M.F. (Maurizio), Felix, S.B. (Stephan), Fischer-Posovszky, P. (Pamela), Folsom, A.R. (Aaron), Friedrich, N. (Nele), Freimer, N.B. (Nelson), Fu, M. (Mao), Gaget, S. (Stefan), Gejman, P.V. (Pablo), Geus, E.J.C. (Eco) de, Gieger, C. (Christian), Gjesing, A.P. (Anette), Goel, A. (Anuj), Goyette, P. (Philippe), Grallert, H. (Harald), Gräßler, J. (Jürgen), Greenawalt, D. (Danielle), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Guiducci, C. (Candace), Hartikainen, A.L., Hassanali, N. (Neelam), Hall, A.S. (Alistair), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Heath, A.C. (Andrew), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hinney, A. (Anke), Hofman, A. (Albert), Homuth, G. (Georg), Hui, J. (Jennie), Igl, W. (Wilmar), Iribarren, C. (Carlos), Isomaa, B. (Bo), Jacobs, K.B. (Kevin), Jarick, I. (Ivonne), Jewell, E. (Eelizabeth), John, U. (Ulrich), Jørgensen, T. (Torben), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaakinen, M. (Marika), Kajantie, E. (Eero), Kaplan, R.C. (Robert), Kathiresan, S. (Sekar), Kettunen, J. (Johannes), Kinnunen, L. (Leena), Knowles, J.W. (Joshua), Kolcic, I. (Ivana), König, I.R. (Inke), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kusisto, J. (Johanna), Kraft, P. (Peter), Kvaløy, K. (Kirsti), Laitinen, J. (Jaana), Lantieri, O. (Olivier), Lanzani, C. (Chiara), Launer, L.J. (Lenore), Lecoeur, C. (Cécile), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Liu, J. (Jianjun), Lokki, M.L., Lorentzon, M. (Mattias), Luben, R.N. (Robert), Ludwig, B. (Barbara), Manunta, P. (Paolo), Marek, D. (Diana), Marre, M. (Michel), Martin, N.G. (Nicholas), McArdle, W.L. (Wendy), McCarthy, M.I. (Mark), McKnight, B. (Barbara), Meitinger, T. (Thomas), Melander, O. (Olle), Meyre, D. (David), Midthjell, K. (Kristian), Montgomery, G.W. (Grant), Morken, M.A. (Mario), Morris, A.D. (Andrew), Mulic, R. (Rosanda), Ngwa, J.S., Nelis, M. (Mari), Neville, M.J. (Matthew), Nyholt, D.R. (Dale), O'Ddonnell, C.J. (Christopher), O'Rahilly, S. (Stephen), Ong, K. (Ken), Oostra, B.A. (Ben), Paré, G. (Guillaume), Parker, A.N. (Alex), Perola, M. (Markus), Pichler, I. (Irene), Pietilainen, K.H. (Kirsi Hannele), Platou, C.P. (Carl), Polasek, O. (Ozren), Pouta, A. (Anneli), Rafelt, S. (Suzanne), Raitakari, O. (Olli), Rayner, N.W. (Nigel William), Ridderstråle, M. (Martin), Rief, W. (Winfried), Ruokonen, A. (Aimo), Robertson, N.R. (Neil), Rzehak, P. (Peter), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Saramies, J. (Jouko), Savolainen, M.J. (Markku), Schipf, S. (Sabine), Schreiber, S. (Stefan), Schunkert, H. (Heribert), Silander, K. (Kaisa), Sinisalo, J. (Juha), Siscovick, D.S. (David), Smit, J.H. (Jan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Stephens, J. (Jonathan), Surakka, I. (Ida), Swift, A.J. (Amy), Tammesoo, M.L., Tardif, J.-C. (Jean-Claude), Teder-Laving, M. (Maris), Teslovich, T.M. (Tanya), Thompson, J.R. (John), Thomson, B. (Brian), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Meurs, J.B.J. (Joyce) van, OMen, G.J. van, Vatin, V. (Vincent), Viikari, J. (Jorma), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogel, C.I. (Carla), Voight, B.F. (Benjamin), Waite, L. (Lindsay), Wallaschofski, H. (Henri), Walters, G.B. (Bragi), Widen, E. (Elisabeth), Wiegand, S. (Susanna), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witte, D.R. (Deniel), Witteman, J.C.M. (Jacqueline), Xu, J. (Jianfeng), Zhang, Q. (Qunyuan), Zgaga, L. (Lina), Ziegler, A. (Andreas), Zitting, P. (Paavo), Beilby, J.P. (John), FarOqi, I.S. (Ssadaf), Hebebrand, J. (Johannes), Huikuri, H.V. (Heikki), James, A. (Alan), Kähönen, M. (Mika), Levinson, D.F. (Douglas), MacCiardi, F. (Fabio), Nieminen, M.S. (Markku), Ohlsson, C. (Claes), Palmer, C. (Cameron), Ridker, P.M. (Paul), Stumvoll, M. (Michael), Beckmann, J.S. (Jacques), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Caulfield, M. (Mark), Chanock, S.J. (Stephen), Collins, F.S. (Francis), Cupples, L.A. (Adrienne), Eerdmann, J. (Jeanette), Frogue, P. (Philippe), Grönberg, H. (Henrik), Gyllensten, U. (Ulf), Hansen, T. (Torben), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayes, R.B. (Richard), Heinrich, J. (Joachim), Hu, F.B. (Frank), Hveem, K. (Kristian), Illig, T. (Thomas), Järvelin, M.R., Kaprio, J. (Jaakko), Karpe, F. (Fredrik), Khaw, K-T. (Kay-Tee), Kiemeney, L.A.L.M. (Bart), Krude, H., Laakso, M. (Markku), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Munroe, P. (Patricia), Ouwehand, W.H. (Willem), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Pramstaller, P.P. (Peter Paul), Quertermous, T. (Thomas), Reinehr, T. (Thomas), Rissanen, A. (Aila), Rudan, I. (Igor), Samani, N.J. (Nilesh), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Spector, T.D. (Timothy), Tuomilehto, J. (Jaakko), Uda, M. (Manuela), Uitterlinden, A.G. (André), Valle, T.T. (Timo), Wabitsch, M. (Martin), Waeber, G. (Gérard), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wilson, J.F. (James), Wright, A.F. (Alan), Zillikens, M.C. (Carola), ChatterjE, N. (Nilanjan), McCarroll, S.A. (Steve), Purcell, S. (Shaun), Schadt, E.E. (Eric), Visscher, P.M. (Peter), Assimes, T.L. (Themistocles), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Haritunians, T. (Talin), Hunter, D.J. (David), Mohlke, K.L. (Karen), O'ConneL, J.R. (Jeffrey), Peltonen, L. (Leena Johanna), SchleSinger, D. (David), Strachan, D.P. (David), Watanabe, R.M. (Richard), Duijn, C.M. (Cornelia) van, Wichmann, H.E. (Heinz Erich), Frayling, T.M. (Timothy), Thorsteinsdottir, U. (Unnur), Abecasis, G.R. (Gonçalo), Boehnke, M. (Michael), StefanSon, K. (Kari), North, K.E. (Kari), McArthy, M.I. (Mark), Hirschhorn, J.N. (Joel), IngelSon, E. (Erik), Loos, R.J.F. (Ruth), and Weedon, M.N. (Michael)
- Abstract
Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS 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 aSociated loci may provide new insights into human body weight regulation.
- Published
- 2010
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21. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- Author
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Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, 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, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, 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, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, 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, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, 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, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, 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, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, 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, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, 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, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, 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, Kaehoenen, 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, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, 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, PEH, 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, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, Loos, RJF, Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, 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, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, 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, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, 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, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, 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, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, 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, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, 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, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, 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, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, 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, Kaehoenen, 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, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, 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, PEH, 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, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, and Loos, RJF
- 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
22. Molecular genetics of obesity
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Hinney, A, Scherag, A, Friedel, S, Ganz Vogel, CI, Jarick, I, Schäfer, H, Hebebrand, J, Hinney, A, Scherag, A, Friedel, S, Ganz Vogel, CI, Jarick, I, Schäfer, H, and Hebebrand, J
- Published
- 2009
23. Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder
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Jarick, I, primary, Volckmar, A-L, additional, Pütter, C, additional, Pechlivanis, S, additional, Nguyen, T T, additional, Dauvermann, M R, additional, Beck, S, additional, Albayrak, Ö, additional, Scherag, S, additional, Gilsbach, S, additional, Cichon, S, additional, Hoffmann, P, additional, Degenhardt, F, additional, Nöthen, M M, additional, Schreiber, S, additional, Wichmann, H-E, additional, Jöckel, K-H, additional, Heinrich, J, additional, Tiesler, C M T, additional, Faraone, S V, additional, Walitza, S, additional, Sinzig, J, additional, Freitag, C, additional, Meyer, J, additional, Herpertz-Dahlmann, B, additional, Lehmkuhl, G, additional, Renner, T J, additional, Warnke, A, additional, Romanos, M, additional, Lesch, K-P, additional, Reif, A, additional, Schimmelmann, B G, additional, Hebebrand, J, additional, Scherag, A, additional, and Hinney, A, additional
- Published
- 2012
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24. A genome-wide association meta-analysis identifies new childhood obesity loci
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Bradfield JP, -, primary, Taal HR, -, additional, Timpson NJ, -, additional, Scherag A, -, additional, Lecoeur C, -, additional, Warrington NM, -, additional, Hypponen E, -, additional, Holst C, -, additional, Valcarcel B, -, additional, Thiering E, -, additional, Salem RM, -, additional, Schumacher FR, -, additional, Cousminer DL, -, additional, Sleiman PM, -, additional, Zhao J, -, additional, Berkowitz RI, -, additional, Vimaleswaran KS, -, additional, Jarick I, -, additional, Pennell CE, -, additional, Evans DM, -, additional, St Pourcain B, -, additional, Berry DJ, -, additional, Mook-Kanamori DO, -, additional, Hofman A, -, additional, Rivadeneira F, -, additional, Uitterlinden AG, -, additional, Van Duijn CM, -, additional, Van der Valk RJ, -, additional, De Jongste JC, -, additional, Postma DS, -, additional, Boomsma DI, -, additional, Gauderman WJ, -, additional, Hassanein MT, -, additional, Lindgren CM, -, additional, Mägi R, -, additional, Boreham CA, -, additional, Neville CE, -, additional, Moreno LA, -, additional, Elliott P, -, additional, Pouta A, -, additional, Hartikainen AL, -, additional, Li M, -, additional, Raitakari O, -, additional, Lehtimäki T, -, additional, Eriksson JG, -, additional, Palotie A, -, additional, Dallongeville J, -, additional, Das S, -, additional, Deloukas P, -, additional, McMahon G, -, additional, Ring SM, -, additional, Kemp JP, -, additional, Buxton JL, -, additional, Blakemore AI, -, additional, Bustamante M, -, additional, Guxens M, -, additional, Hirschhorn JN, -, additional, Gillman MW, -, additional, Kreiner-Møller E, -, additional, Bisgaard H, -, additional, Gilliland FD, -, additional, Heinrich J, -, additional, Wheeler E, -, additional, Barroso I, -, additional, O'Rahilly S, -, additional, Meirhaeghe A, -, additional, Sørensen TI, -, additional, Power C, -, additional, Palmer LJ, -, additional, Hinney A, -, additional, Widen E, -, additional, Farooqi IS, -, additional, McCarthy MI, -, additional, Froguel P, -, additional, Meyre D, -, additional, Hebebrand J, -, additional, Jarvelin MR, -, additional, Jaddoe VW, -, additional, Smith GD, -, additional, Hakonarson H, -, additional, and Grant, SF, additional
- Published
- 2012
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25. Addendum: Genome-wide association study in German patients with attention deficit/hyperactivity disorder
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Hinney, Anke, Scherag, Andre, Jarick, I., Albayrak, Özgür, Putter, C., Pechlivanis, Sonali, Dauvermann, M. R., Beck, S., Weber, H., Scherag, S., Nguyen, T. T., Volckmar, A. L., Knoll, N., Faraone, S. V., Neale, B. M., Franke, B., Cichon, S., Hoffmann, P., Nothen, M. M., Schreiber, S., Jöckel, Karl-Heinz, Wichmann, H. E., Freitag, C., Lempp, T., Meyer, J., Gilsbach, S., Herpertz-Dahlmann, B., Sinzig, J., Lehmkuhl, G., Renner, T. J., Warnke, A., Romanos, M., Lesch, K. P., Reif, A., von Schimmelmann, Benno, Hebebrand, Johannes, and Psychiat GWAS Consortium, xxx
- Subjects
Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Medizin ,Genetics (clinical) - Published
- 2012
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- View/download PDF
26. Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder
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Volckmar, A-L, Dauvermann, M R, Schimmelmann, B G, Schreiber, S, Walitza, S, Tiesler, C M T, Cichon, S, Scherag, A, Freitag, C, Jarick, I, Herpertz-Dahlmann, B, Reif, A, Heinrich, J, Beck, S, Hinney, A, Albayrak, O, Degenhardt, F, Lesch, K-P, Sinzig, J, Wichmann, H-E, Nguyen, T T, Lehmkuhl, G, Pechlivanis, S, Gilsbach, S, Scherag, S, Warnke, A, Meyer, J, Hebebrand, J, Pütter, C, Nöthen, M M, Renner, T J, Faraone, S V, Romanos, M, Hoffmann, P, and Jöckel, K-H
- Subjects
mental disorders ,3. Good health - 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.Molecular Psychiatry advance online publication, 20 November 2012; doi:10.1038/mp.2012.161.
27. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- Author
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Zhaoming Wang, André Scherag, James F. Wilson, Nancy L. Heard-Costa, Ingrid B. Borecki, Sang Hong Lee, Veronique Vitart, Zoltán Kutalik, Jeffrey R. O'Connell, Mieke D. Trip, Lu Qi, Peter Vollenweider, Jennifer L. Bragg-Gresham, Davide Gentilini, Kees Hovingh, Lynda M. Rose, Carolin Pütter, Martin Farrall, Albert V. Smith, Nicholas G. Martin, Tõnu Esko, David J. Hunter, Georg Homuth, Liming Liang, Yudi Pawitan, Winfried März, George Dedoussis, Irene Mateo Leach, Nicholas J. Wareham, Lars Lind, Thomas Illig, Andrew P. Morris, Daniele Cusi, Jouke-Jan Hottenga, Tove Fall, Themistocles L. Assimes, Massimo Mangino, Dmitry Shungin, Kari Stefansson, Anne U. Jackson, Inês Barroso, Sarah E. Medland, Lude Franke, Karen L. Mohlke, Folkert W. Asselbergs, Sarah E. Hunt, Gudmar Thorleifsson, Pablo V. Gejman, Serena Sanna, Mark I. McCarthy, David M. Evans, Joel N. Hirschhorn, Alan F. Wright, Sarah H. Wild, Patricia B. Munroe, Marcel Bruinenberg, Gonneke Willemsen, Ulf de Faire, Markku Laakso, Marja-Liisa Lokki, Andrew C. Heath, Jing Hua Zhao, Lavinia Paternoster, Jana V. van Vliet-Ostaptchouk, Sailaja Vedantam, Danyu Lin, Eric E. Schadt, Stefano Signorini, Harald Grallert, Tsegaselassie Workalemahu, Jonathan Tyrer, Albert Hofman, George Nicholson, Patrik K. E. Magnusson, Arthur W. Musk, Jian Yang, Vilmundur Gudnason, Robert C. Kaplan, Panos Deloukas, Nilesh J. Samani, Inke R. König, Frank B. Hu, Paul M. Ridker, Tamara B. Harris, Bruce H. R. Wolffenbuttel, Ellen A. Nohr, Sarah Edkins, Lambertus A. Kiemeney, Anke Hinney, Eric Boerwinkle, Klaus Stark, Ben A. Oostra, Barbara Thorand, Unnur Thorsteinsdottir, Meena Kumari, Evelin Mihailov, Caroline S. Fox, Michael Boehnke, Aroon D. Hingorani, Jonathan Stephens, Kathleen Stirrups, Inga Prokopenko, Anke Tönjes, Lili Milani, John Beilby, Carlos Iribarren, Kari E. North, Cécile Lecoeur, So-Youn Shin, Marjo-Riitta Järvelin, Matti Uusitupa, Åsa Johansson, Nancy L. Pedersen, Krista Fischer, Fernando Rivadeneira, Wolfgang Koenig, Fredrik Karpe, Antti Jula, Lindsay L. Waite, Gérard Waeber, Mustafa Atalay, Heribert Schunkert, Narisu Narisu, Sita H. Vermeulen, Bernhard R. Winkelmann, Guo Li, Anders Hamsten, Elizabeth K. Speliotes, Ivonne Jarick, Sirkka Keinänen-Kiukaanniemi, L. Adrienne Cupples, Ruth J. F. Loos, Martina Müller-Nurasyid, David-Alexandre Trégouët, Claudia Langenberg, Willem H. Ouwehand, Julius S. Ngwa, Jennifer E. Huffman, H-Erich Wichmann, Amy J. Swift, Marco M Ferrario, Leif Groop, Henrik Grönberg, Peter M. Visscher, Claes Ohlsson, Markku S. Nieminen, Aparna Radhakrishnan, Harold Snieder, Devin Absher, Albertine J. Oldehinkel, Erik Ingelsson, Anna Maria Di Blasio, M. Carola Zillikens, Veikko Salomaa, Colin N. A. Palmer, Lori L. Bonnycastle, Teresa Ferreira, Ronald P. Stolk, Annette Peters, Philippe Froguel, Michael Stumvoll, David Schlessinger, Maria Dimitriou, Timo Saaristo, Cristen J. Willer, Jarmo Virtamo, Jorma Viikari, Alena Stančáková, Mika Kivimäki, Paolo Brambilla, Jaakko Tuomilehto, Dorret I. Boomsma, Harry Campbell, Jianjun Liu, Daniel I. Chasman, Gonçalo R. Abecasis, Ilja M. Nolte, Karl-Heinz Jöckel, Reedik Mägi, Pamela A. F. Madden, Jaana Laitinen, Sonja I. Berndt, Frank Kee, Marcus E. Kleber, Jacqueline C.M. Witteman, Jouko Saramies, Francis S. Collins, Johan G. Eriksson, Melanie M. van der Klauw, Yi-Juan Hu, John F. Peden, Markus Perola, Henri Wallaschofski, Jean Ferrières, Elena Tremoli, Marjolein J. Peters, Olli T. Raitakari, Claudia Lamina, Sekar Kathiresan, Mary F. Feitosa, Diana Kuh, Tim D. Spector, Paul W. Franks, Gerjan Navis, Martin den Heijer, Christian Gieger, Kevin B. Jacobs, Andrea Ganna, Timothy M. Frayling, Iris M. Heid, Bernhard O. Boehm, Eleanor Wheeler, Sonali Pechlivanis, Miriam F. Moffatt, Brenda W.J.H. Penninx, Anna-Liisa Hartikainen, Augusto Rendon, Stefan Schreiber, Stephen J. Chanock, Andrew R. Wood, Jianxin Shi, Najaf Amin, Lenore J. Launer, Michael A. Province, Jeanette Erdmann, Mattias Lorentzon, Hugh Watkins, Johanna Kuusisto, John-Olov Jansson, David P. Strachan, Anne E. Justice, Toby Johnson, Cornelia M. van Duijn, Niina Eklund, Samuli Ripatti, Aarno Palotie, Aldi T. Kraja, Michael Preuss, Rona J. Strawbridge, Ozren Polasek, Elisabeth Widen, Barbara McKnight, Mariano Dei, Vincent Mooser, Josine L. Min, Caroline Hayward, Mika Kähönen, Peter P. Pramstaller, Femmie de Vegt, Rainer Rauramaa, Douglas F. Levinson, Diana Marek, Antonio Liuzzi, Stefan Gustafsson, Andrew A. Hicks, Gemma Cadby, Damien C. Croteau-Chonka, Mark J. Caulfield, Boris Skrobek, Lyle J. Palmer, Alexander Teumer, Ken K. Ong, Ulf Gyllensten, Anneli Pouta, Anuj Goel, Eva Albrecht, Kristian Hveem, Inger Njølstad, David Meyre, Ida Surakka, Francesca Frau, Paolo Manunta, Sabine Schipf, Carolina Medina-Gomez, Kay-Tee Khaw, Alan R. Sanders, Thorkild I. A. Sørensen, André G. Uitterlinden, Alistair S. Hall, Felix R. Day, Karol Estrada, Jennifer G. Sambrook, Eirini V. Theodoraki, Valgerdur Steinthorsdottir, Cecilia M. Lindgren, Talin Haritunian, Benjamin M. Neale, Juha Sinisalo, Kati Kristiansson, Thomas W. Winkler, Pim van der Harst, Peter S. Chines, Joyce B. J. van Meurs, Wendy L. McArdle, Andrew Wong, Grant W. Montgomery, Terho Lehtimäki, Igor Rudan, Keri L. Monda, John M. C. Connell, Jian'an Luan, Per Hall, Joshua C. Randall, Anthony J. Balmforth, Chris Power, Philippe Amouyel, Andres Metspalu, Johannes Hebebrand, Andrew D. Morris, Jaana Lindström, Liesbeth Vandenput, William O.C.M. Cookson, Hanneke Basart, Stavroula Kanoni, Elina Hyppönen, Christian Hengstenberg, Thomas W. Mühleisen, Kari Kuulasmaa, Timo A. Lakka, Nicole Soranzo, Bruce M. Psaty, Antony P. Attwood, Epidemiology, Clinical Genetics, Surgery, Erasmus School of Social and Behavioural Sciences, Public Health, Internal Medicine, Immunology, Child and Adolescent Psychiatry / Psychology, Internal medicine, Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Lifestyle, overweight and diabetes, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Other departments, Vascular Medicine, Biological Psychology, Cognitive Psychology, AIMMS, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Life Course Epidemiology (LCE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Medical Research Council (MRC), Berndt, Sonja I, Gustafsson, Stefan, Mägi, Reedik, Ganna, Andrea, Lee, Sang Hong, Hyppönen, Elina Tuulikki, Ingelsson, Erik, Berndt, Si, Feitosa, Mf, Justice, Ae, Monda, Kl, CROTEAU CHONKA, Dc, Day, Fr, Jackson, Au, Randall, Jc, Willer, Cj, Winkler, Tw, Wood, Ar, Hu, Yj, Lee, Sh, Lin, Dy, Min, Jl, Neale, Bm, BRAGG GRESHAM, Jl, DEN HEIJER, M, Hottenga, Jj, Huffman, Je, Johansson, A, Kleber, Me, König, Ir, Mcardle, Wl, MEDINA GOMEZ, C, MÜLLER NURASYID, M, Nolte, Im, Peters, Mj, Rose, Lm, Smith, Av, Strawbridge, Rj, Trip, Md, VAN VLIET OSTAPTCHOUK, Jv, Waite, Ll, Zhao, Jh, Asselbergs, Fw, Attwood, Ap, Balmforth, Aj, Bonnycastle, Ll, Chasman, Di, Connell, Jm, Cookson, Wo, DE FAIRE, U, DE VEGT, F, Evans, Dm, Ferrario, Mm, Gejman, Pv, Hartikainen, Al, HEARD COSTA, Nl, Heath, Ac, Hu, Fb, Hunt, Se, Jacobs, Kb, Jansson, Jo, Khaw, Kt, Kraja, At, Laitinen, Jh, Lakka, Ta, Launer, Lj, Lokki, Ml, Madden, Pa, Magnusson, Pk, Manunta, Paolo, MATEO LEACH, I, Medland, Se, Montgomery, Gw, Mühleisen, Tw, Munroe, Pb, Musk, Aw, Nohr, Ea, Ong, Kk, Oostra, Ba, Palmer, Cn, Peden, Jf, Pramstaller, Pp, Saaristo, Te, Sambrook, Jg, Sanders, Ar, Shin, Sy, Stephens, Jc, Stolk, Rp, Swift, Aj, Theodoraki, Ev, Tregouet, Da, VAN DER KLAUW, Mm, VAN MEURS, Jb, Vermeulen, Sh, Wild, Sh, Winkelmann, Br, Witteman, Jc, Wolffenbuttel, Bh, Wright, Af, Zillikens, Mc, Boehm, Bo, Boomsma, Di, Caulfield, Mj, Chanock, Sj, Cupples, La, Dedoussis, Gv, Eriksson, Jg, Franks, Pw, Harris, Tb, Hicks, Aa, Hovingh, Kg, Jarvelin, Mr, Jöckel, Kh, KEINANEN KIUKAANNIEMI, Sm, Kiemeney, La, Levinson, Df, Martin, Ng, Morris, Ad, Oldehinkel, Aj, Ouwehand, Wh, Palmer, Lj, Province, Ma, Psaty, Bm, Ridker, Pm, Samani, Nj, Sørensen, Ti, Spector, Td, Uitterlinden, Ag, VAN DER HARST, P, Wareham, Nj, Wichmann, He, Wilson, Jf, Abecasis, Gr, Assimes, Tl, Borecki, Ib, Groop, Lc, Heid, Im, Kaplan, Rc, Moffatt, Mf, Mohlke, Kl, O'Connell, Jr, Schadt, Ee, Strachan, Dp, VAN DUIJN, Cm, Visscher, Pm, DI BLASIO, Am, Hirschhorn, Jn, Lindgren, Cm, Morris, Ap, Mccarthy, Mi, Speliotes, Ek, North, Ke, Loos, Rj, and Ingelsson, E.
- Subjects
Netherlands Twin Register (NTR) ,Linkage disequilibrium ,SORTILIN ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Medizin ,Genome-wide association study ,Aetiology, screening and detection [ONCOL 5] ,polymorphism ,Body Mass Index ,0302 clinical medicine ,Missing heritability problem ,MISSING HERITABILITY ,EXTREME OBESITY ,CONFER RISK ,POPULATION ,Genetics & Heredity ,2. Zero hunger ,Genetics ,Medical And Health Sciences ,0303 health sciences ,education.field_of_study ,Anthropometry ,COMMON VARIANTS ,Single Nucleotide ,ASSOCIATION ,Biological Sciences ,Anthropometry, Body Height ,genetics, Body Mass Index, Case-Control Studies, European Continental Ancestry Group ,genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Obesity ,genetics, Phenotype, Polymorphism ,genetics, Quantitative Trait Loci, Waist-Hip Ratio ,Phenotype ,Life Sciences & Biomedicine ,EXPRESSION ,Genotype ,Missing heritabillity ,Population ,European Continental Ancestry Group ,Quantitative Trait Loci ,EARLY-ONSET ,Genomics ,Biology ,Quantitative trait locus ,Polymorphism, Single Nucleotide ,Article ,White People ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,Meta-Analysis as Topic ,SDG 3 - Good Health and Well-being ,Humans ,Genetic Predisposition to Disease ,Obesity ,body height/genetics ,Polymorphism ,Allele ,Genetik ,education ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,030304 developmental biology ,Science & Technology ,Waist-Hip Ratio ,BMI, height, WHR, obesity, GWS ,ta3121 ,Genetic architecture ,Body Height ,BODY-MASS INDEX ,Case-Control Studies ,gene ,stature ,height ,030217 neurology & neurosurgery ,Developmental Biology ,Genome-Wide Association Study - Abstract
Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups. © 2013 Nature America, Inc. All rights reserved.
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28. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts
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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
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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
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29. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
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Fredrik Karpe, Ivonne Jarick, Julius S. Ngwa, Alan F. Wright, Robert Luben, Aaron R. Folsom, Sailaja Vedantam, Veikko Salomaa, Markku J. Savolainen, Robert Clarke, Shah Ebrahim, Thomas A. Buchanan, Mao Fu, Albert Hofman, Philippe Goyette, Camilla H. Sandholt, Fabio Macciardi, Elizabeth K. Speliotes, Barbara McKnight, Anne McCarthy, Mika Kaehoenen, Christian Gieger, Jorma S. A. Viikari, Nicholas J. Timpson, Kirsti Kvaløy, Douglas F. Levinson, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Andrew A. Hicks, Niina Pellikka, Charles C. White, Leena Peltonen, Reedik Maegi, John-Olov Jansson, Qunyuan Zhang, Claudia Lamina, Robert C. Kaplan, Peter M. Visscher, Laura J. Scott, Claes Ohlsson, Brian Thomson, Jubao Duan, Heikki V. Huikuri, Stephen O'Rahilly, Anette P. Gjesing, David P. Strachan, Caroline S. Fox, Sekar Kathiresan, Anna-Liisa Hartikainen, Johannes Kettunen, Maris Teder-Laving, Erik Ingelsson, Mario A. Morken, Peter Kovacs, Elisabeth Widen, Caroline Hayward, Eleanor Wheeler, Jing Hua Zhao, Vilmundur Gudnason, Panos Deloukas, Jacqueline C. M. Witteman, Gert-Jan B. van Ommen, Eric Boerwinkle, Martin Wabitsch, Christian Hengstenberg, Beverley Balkau, Thor Aspelund, Neelam Hassanali, Paul M. Ridker, Nicole L. Glazer, Joyce B. J. van Meurs, Michel Marre, Alan James, Ben A. Oostra, David Meyre, Ida Surakka, Stefan Schreiber, Nigel W. Rayner, Heribert Schunkert, Thomas Quertermous, Stefan Gustafsson, Peter Kraft, Benjamin F. Voight, Irene Pichler, Olle Melander, Ozren Polasek, Antti Jula, Alan R. Sanders, Andrew R. Wood, Yoav Ben-Shlomo, Thomas Illig, Jianjun Liu, Gerard Waeber, André G. Uitterlinden, Torben Hansen, Helene Alavere, André Scherag, Paolo Manunta, Johannes Hebebrand, Themistocles L. Assimes, Stefan R. Bornstein, Jaakko Tuomilehto, Morris Brown, Jianfeng Xu, Yii-Der Ida Chen, Nancy L. Heard-Costa, Cristen J. Willer, Henrik Greonberg, Guillaume Lettre, John R. Thompson, Inês Barroso, John R. B. Perry, Andreas Ziegler, James F. Wilson, Christopher J. O'Donnell, Maurizio F. Facheris, Robert Lawrence, Jan Smit, Lyle J. Palmer, Ulf Gyllensten, Richard B. Hayes, Shengxu Li, Barbara Ludwig, Larry D. Atwood, Valgerdur Steinthorsdottir, Sabine Schipf, Jouko Saramies, Tanja Boes, Martin Ridderstråle, Jennie Hui, Lina Zgaga, Susann Scherag, Alexandra I. F. Blakemore, Marjolein Peters, Timo T. Valle, Nelson B. Freimer, Kay-Tee Khaw, Amy J. Swift, Michael Stumvoll, Miriam F. Moffatt, Cecilia M. Lindgren, Ayellet V. Segrè, Neil Robertson, Richard N. Bergman, Francis S. Collins, Ryan P. Welch, Mari-Liis Tammesoo, Devin Absher, Tamara B. Harris, Kari E. North, Manuela Uda, Karen L. Mohlke, Inga Prokopenko, Per Hall, Gudmar Thorleifsson, Marjo-Riitta Järvelin, Guillaume Paré, Stefan Gaget, G. Bragi Walters, Michael N. Weedon, Jean-Claude Tardif, Mary F. Feitosa, Anke Toenjes, Ken K. Ong, Cécile Lecoeur, Paavo Zitting, David S. Siscovick, Chih-Mei Chen, Peter Almgren, Anneli Pouta, Philippe Froguel, Pekka Jousilahti, Jaakko Kaprio, Maria Teresa Sciarrone Alibrandi, Sophie van Wingerden, Steven A. McCarroll, Oluf Pedersen, Shaun Purcell, Veronique Vitart, Leena Kinnunen, Markus Perola, Jacques S. Beckmann, Vincent Vatin, Christopher J. Groves, Zoltán Kutalik, Lu Qi, Volker Hoesel, Seppo Koskinen, Suzanne Rafelt, Anke Hinney, Annette Peters, David Schlessinger, Eero Kajantie, Jian Yang, Nicholas G. Martin, Joshua W. Knowles, Kristian Midthjell, Olivier Lantieri, Dorret I. Boomsma, Harry Campbell, Ulrich John, Kirsi H. Pietilaeinen, George Davey Smith, Carl G. P. Platou, Sarah H. Wild, Patricia B. Munroe, Iris M. Heid, Diana Marek, Michael Boehnke, Andres Metspalu, Hana Lango Allen, Peter Rzehak, Christine Cavalcanti-Proença, M. Carola Zillikens, Åsa Johansson, Anuj Goel, Andrew T. Hattersley, Massimo Mangino, Michael E. Goddard, Tim D. Spector, Winfried Rief, Jonathan Tyrer, Lachlan J. M. Coin, Peter P. Pramstaller, Narisu Narisu, John Beilby, Jonathan Stephens, Christina Barlassina, Pamela Fischer-Posovszky, Brenda W.J.H. Penninx, Kaisa Silander, Richard H. Myers, Jouke-Jan Hottenga, Eric E. Schadt, Francesco P. Cappuccio, Martin den Heijer, Fernando Rivadeneira, Lindsay L. Waite, Wilmar Igl, Igor Rudan, Manjinder S. Sandhu, Debbie A Lawlor, Kristian Hveem, Susanna Wiegand, Mari Nelis, Thomas Reinehr, Elisabeth Thiering, Inke R. Koenig, Stephan B. Felix, Fredrik Wiklund, Ian N. M. Day, Willem H. Ouwehand, Peter Schwarz, Richard M. Watanabe, Keri L. Monda, Kari Stefansson, Gudny Eiriksdottir, H-Erich Wichmann, Jianxin Shi, Najaf Amin, Carlos Iribarren, Heiko Krude, Dale R. Nyholt, Lenore J. Launer, Stephen J. Chanock, Harald Grallert, Hugh Watkins, Juergen Graessler, Tsegaselassie Workalemahu, Jeanette Erdmann, Mattias Lorentzon, Leif Groop, Teresa Ferreira, Chiara Lanzani, Johanna Kuusisto, Johan G. Eriksson, Tõnu Esko, Torben Jørgensen, Robert J. Weyant, Michael Preuss, Lambertus A. Kiemeney, Daniel I. Chasman, Daniel R. Witte, Kevin B. Jacobs, Nicole Soranzo, John M. C. Connell, Soumya Raychaudhuri, Jian'an Luan, Joshua C. Randall, Joachim Heinrich, Anthony J. Balmforth, Eva Fisher, Elizabeth S. Jewell, Alice M. Arnold, Nele Friedrich, Olli T. Raitakari, Henri Wallaschofski, Jeffrey R. O'Connell, Terho Lehtimaeki, Marika Kaakinen, Heather M. Stringham, Bo Isomaa, I. Sadaf Farooqi, Anna L. Dixon, Anne U. Jackson, Mark I. McCarthy, Lori L. Bonnycastle, Aila Rissanen, Joel N. Hirschhorn, Nilesh J. Samani, Aimo Ruokonen, Frank B. Hu, L. Adrienne Cupples, Amanda J. Bennett, Shamika Ketkar, Ruth J. F. Loos, Nicholas J. Wareham, Tiinamaija Tuomi, Timothy M. Frayling, Ulla Sovio, Georg Homuth, Liming Liang, Heiner Boeing, Unnur Thorsteinsdottir, Ingrid B. Borecki, Danielle M. Greenawalt, Rosanda Mulić, Ivana Kolcic, Talin Haritunians, Mark J. Caulfield, Marja-Liisa Lokki, Tanya M. Teslovich, Paul Elliott, Matt Neville, Nilanjan Chatterjee, Albert V. Smith, Andrew P. Morris, Fabio Busonero, Gonçalo R. Abecasis, Jaana Laitinen, Michael R. Erdos, Candace Guiducci, Lee M. Kaplan, Aki S. Havulinna, Pablo V. Gejman, Alan R. Shuldiner, Serena Sanna, David J. Hunter, Sonja I. Berndt, Carla I. G. Vogel, Alistair S. Hall, Karol Estrada, Sven Bergmann, Thomas Meitinger, Gonneke Willemsen, Andrew C. Heath, Katja K.H. Aben, Markku Laakso, Juha Sinisalo, Tuomas O. Kilpelaenen, Mark E. Cooper, Heike Biebermann, Eco J. C. de Geus, Grant W. Montgomery, Sophie Visvikis-Siest, Thomas W. Winkler, Ju-Hyun Park, Alex N. Parker, Peter S. Chines, James Nemesh, Nabila Bouatia-Naji, Wendy L. McArdle, Roberto Elosua, Markku S. Nieminen, Psychiatry, NCA - Anxiety & Depression, EMGO - Mental health, Epidemiology, Internal Medicine, Clinical Genetics, Radiology & Nuclear Medicine, Erasmus MC other, Public Health, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, MAGIC, Procardis Consortium, Medical Research Council (MRC), Speliotes, Ek, Willer, Cj, Berndt, Si, Monda, Kl, Thorleifsson, G, Jackson, Au, Allen, Hl, 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, P, 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, A, Havulinna, A, 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, Magic, Manunta, Paolo, 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, J, 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, M, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, D, 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, I, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, M, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, J, Boeing, H, Boerwinkle, E, Boomsma, Di, Caulfield, Mj, Chanock, Sj, Collins, F, 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, Procardis, Consortium, Wilson, Jf, Wright, Af, Zillikens, Mc, Chatterjee, N, Mccarroll, Sa, Purcell, S, Schadt, Ee, Visscher, Pm, Assimes, Tl, Borecki, Ib, Deloukas, P, Fox, C, 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
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Netherlands Twin Register (NTR) ,Medizin ,Genome-wide association study ,Aetiology, screening and detection [ONCOL 5] ,FTO gene ,Body Mass Index ,0302 clinical medicine ,SH2B1 ,GASTRIC-INHIBITORY POLYPEPTIDE ,ADULT OBESITY ,Glucose homeostasis ,Body Size ,GENETICS & HEREDITY ,2. Zero hunger ,Genetics ,Genetics & Heredity ,RISK ,0303 health sciences ,Neuronal growth regulator 1 ,Genetics of obesity ,COMMON VARIANTS ,Chromosome Mapping ,11 Medical And Health Sciences ,Body Height/genetics ,Body Size/genetics ,Body Weight/genetics ,European Continental Ancestry Group/genetics ,Genetic Predisposition to Disease/genetics ,Genome-Wide Association Study ,Humans ,Obesity/genetics ,Polymorphism, Single Nucleotide ,FAT MASS ,Body Height/*genetics *Body Mass Index Body Size/genetics Body Weight/*genetics *Chromosome Mapping European Continental Ancestry Group/genetics Genetic Predisposition to Disease/genetics Genome-Wide Association Study Humans Obesity/genetics Polymorphism, Single Nucleotide ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,MELANOCORTIN-4 RECEPTOR GENE ,Life Sciences & Biomedicine ,European Continental Ancestry Group ,EARLY-ONSET ,030209 endocrinology & metabolism ,Locus (genetics) ,Biology ,Article ,White People ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,body mass index ,genome-wide association ,meta-analysis ,Genetic Predisposition to Disease ,Obesity ,GENOME-WIDE ASSOCIATION ,FTO GENE ,030304 developmental biology ,Science & Technology ,genome-wide association gastric-inhibitory polypeptide melanocortin-4 receptor gene glucose-homeostasis common variants adult obesity early-onset fat mass risk metaanalysis ,Body Weight ,06 Biological Sciences ,MAGIC ,Body Height ,GLUCOSE-HOMEOSTASIS ,Procardis Consortium ,Body mass index ,Developmental Biology - Abstract
Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS 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 aSociated loci may provide new insights into human body weight regulation. © 2010 Nature America, Inc. All rights reserved.
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- 2010
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30. Analysis of Genes Involved in Body Weight Regulation by Targeted Re-Sequencing.
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Volckmar AL, Han CT, Pütter C, Haas S, Vogel CI, Knoll N, Struve C, Göbel M, Haas K, Herrfurth N, Jarick I, Grallert H, Schürmann A, Al-Hasani H, Hebebrand J, Sauer S, and Hinney A
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- Adolescent, Adult, Child, Computer Simulation, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Linkage Disequilibrium genetics, Male, Obesity genetics, Quality Control, Reproducibility of Results, Thinness genetics, Body Weight genetics, Gene Expression Regulation, High-Throughput Nucleotide Sequencing methods
- Abstract
Introduction: Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing., Methods: We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) ≥ 99th percentile and 176 lean adults (BMI ≤ 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults., Results and Conclusion: We detected 20 different non-synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (pTDT = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted.
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- 2016
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31. Fine Mapping of a GWAS-Derived Obesity Candidate Region on Chromosome 16p11.2.
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Volckmar AL, Song JY, Jarick I, Pütter C, Göbel M, Horn L, Struve C, Haas K, Knoll N, Grallert H, Illig T, Reinehr T, Wang HJ, Hebebrand J, and Hinney A
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- Adaptor Proteins, Signal Transducing genetics, Adolescent, Adult, Arylsulfotransferase genetics, Body Mass Index, Child, Chromosome Mapping, Female, Genotype, Humans, Linkage Disequilibrium, Male, Middle Aged, Mitochondrial Proteins genetics, Obesity pathology, Peptide Elongation Factor Tu genetics, Polymorphism, Single Nucleotide, Receptors, Lipoprotein genetics, Chromosomes, Human, Pair 16, Genome-Wide Association Study, Obesity genetics
- Abstract
Introduction: Large-scale genome-wide association studies (GWASs) have identified 97 chromosomal loci associated with increased body mass index in population-based studies on adults. One of these SNPs, rs7359397, tags a large region (approx. 1MB) with high linkage disequilibrium (r2>0.7), which comprises five genes (SH2B1, APOBR, sulfotransferases: SULT1A1 and SULT1A2, TUFM). We had previously described a rare mutation in SH2B1 solely identified in extremely obese individuals but not in lean controls., Methods: The coding regions of the genes APOBR, SULT1A1, SULT1A2, and TUFM were screened for mutations (dHPLC, SSCP, Sanger re-sequencing) in 95 extremely obese children and adolescents. Detected non-synonymous variants were genotyped (TaqMan SNP Genotyping, MALDI TOF, PCR-RFLP) in independent large study groups (up to 3,210 extremely obese/overweight cases, 485 lean controls and 615 obesity trios). In silico tools were used for the prediction of potential functional effects of detected variants., Results: Except for TUFM we detected non-synonymous variants in all screened genes. Two polymorphisms rs180743 (APOBR p.Pro428Ala) and rs3833080 (APOBR p.Gly369_Asp370del9) showed nominal association to (extreme) obesity (uncorrected p = 0.003 and p = 0.002, respectively). In silico analyses predicted a functional implication for rs180743 (APOBR p.Pro428Ala). Both APOBR variants are located in the repetitive region with unknown function., Conclusion: Variants in APOBR contributed as strongly as variants in SH2B1 to the association with extreme obesity in the chromosomal region chr16p11.2. In silico analyses implied no functional effect of several of the detected variants. Further in vitro or in vivo analyses on the functional implications of the obesity associated variants are warranted.
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- 2015
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32. Mitochondrial DNA variants in obesity.
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Knoll N, Jarick I, Volckmar AL, Klingenspor M, Illig T, Grallert H, Gieger C, Wichmann HE, Peters A, Wiegand S, Biebermann H, Fischer-Posovszky P, Wabitsch M, Völzke H, Nauck M, Teumer A, Rosskopf D, Rimmbach C, Schreiber S, Jacobs G, Lieb W, Franke A, Hebebrand J, and Hinney A
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- Adolescent, Adult, Aged, Case-Control Studies, Female, Haplotypes genetics, Humans, Male, Middle Aged, Sequence Analysis, DNA, Young Adult, DNA, Mitochondrial genetics, Genome-Wide Association Study, Obesity genetics, Polymorphism, Single Nucleotide
- Abstract
Heritability estimates for body mass index (BMI) variation are high. For mothers and their offspring higher BMI correlations have been described than for fathers. Variation(s) in the exclusively maternally inherited mitochondrial DNA (mtDNA) might contribute to this parental effect. Thirty-two to 40 mtDNA single nucleotide polymorphisms (SNPs) were available from genome-wide association study SNP arrays (Affymetrix 6.0). For discovery, we analyzed association in a case-control (CC) sample of 1,158 extremely obese children and adolescents and 435 lean adult controls. For independent confirmation, 7,014 population-based adults were analyzed as CC sample of n = 1,697 obese cases (BMI ≥ 30 kg/m2) and n = 2,373 normal weight and lean controls (BMI<25 kg/m2). SNPs were analyzed as single SNPs and haplogroups determined by HaploGrep. Fisher's two-sided exact test was used for association testing. Moreover, the D-loop was re-sequenced (Sanger) in 192 extremely obese children and adolescents and 192 lean adult controls. Association testing of detected variants was performed using Fisher's two-sided exact test. For discovery, nominal association with obesity was found for the frequent allele G of m.8994G/A (rs28358887, p = 0.002) located in ATP6. Haplogroup W was nominally overrepresented in the controls (p = 0.039). These findings could not be confirmed independently. For two of the 252 identified D-loop variants nominal association was detected (m.16292C/T, p = 0.007, m.16189T/C, p = 0.048). Only eight controls carried the m.16292T allele, five of whom belonged to haplogroup W that was initially enriched among these controls. m.16189T/C might create an uninterrupted poly-C tract located near a regulatory element involved in replication of mtDNA. Though follow-up of some D-loop variants still is conceivable, our hypothesis of a contribution of variation in the exclusively maternally inherited mtDNA to the observed larger correlations for BMI between mothers and their offspring could not be substantiated by the findings of the present study.
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- 2014
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33. Gene set of nuclear-encoded mitochondrial regulators is enriched for common inherited variation in obesity.
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Knoll N, Jarick I, Volckmar AL, Klingenspor M, Illig T, Grallert H, Gieger C, Wichmann HE, Peters A, Hebebrand J, Scherag A, and Hinney A
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- Animals, Case-Control Studies, Disease Models, Animal, Genetic Linkage, Humans, Linkage Disequilibrium, Mitochondria genetics, Oxidative Phosphorylation, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mitochondria metabolism, Obesity genetics, Obesity metabolism
- Abstract
There are hints of an altered mitochondrial function in obesity. Nuclear-encoded genes are relevant for mitochondrial function (3 gene sets of known relevant pathways: (1) 16 nuclear regulators of mitochondrial genes, (2) 91 genes for oxidative phosphorylation and (3) 966 nuclear-encoded mitochondrial genes). Gene set enrichment analysis (GSEA) showed no association with type 2 diabetes mellitus in these gene sets. Here we performed a GSEA for the same gene sets for obesity. Genome wide association study (GWAS) data from a case-control approach on 453 extremely obese children and adolescents and 435 lean adult controls were used for GSEA. For independent confirmation, we analyzed 705 obesity GWAS trios (extremely obese child and both biological parents) and a population-based GWAS sample (KORA F4, n = 1,743). A meta-analysis was performed on all three samples. In each sample, the distribution of significance levels between the respective gene set and those of all genes was compared using the leading-edge-fraction-comparison test (cut-offs between the 50(th) and 95(th) percentile of the set of all gene-wise corrected p-values) as implemented in the MAGENTA software. In the case-control sample, significant enrichment of associations with obesity was observed above the 50(th) percentile for the set of the 16 nuclear regulators of mitochondrial genes (p(GSEA,50) = 0.0103). This finding was not confirmed in the trios (p(GSEA,50) = 0.5991), but in KORA (p(GSEA,50) = 0.0398). The meta-analysis again indicated a trend for enrichment (p(MAGENTA,50) = 0.1052, p(MAGENTA,75) = 0.0251). The GSEA revealed that weak association signals for obesity might be enriched in the gene set of 16 nuclear regulators of mitochondrial genes.
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- 2013
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34. Mutation screen in the GWAS derived obesity gene SH2B1 including functional analyses of detected variants.
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Volckmar AL, Bolze F, Jarick I, Knoll N, Scherag A, Reinehr T, Illig T, Grallert H, Wichmann HE, Wiegand S, Biebermann H, Krude H, Fischer-Posovszky P, Rief W, Wabitsch M, Klingenspor M, Hebebrand J, and Hinney A
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- Adolescent, Adult, Binding Sites genetics, Child, Computational Biology, DNA Mutational Analysis, Female, Gene Frequency genetics, Glycosylation, Humans, Leptin metabolism, Luciferases metabolism, Male, Middle Aged, Phenotype, RNA Splice Sites genetics, Receptors, Leptin genetics, STAT3 Transcription Factor metabolism, Signal Transduction genetics, Transcription Factors metabolism, Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Genetic Predisposition to Disease, Genome-Wide Association Study, Mutation genetics, Obesity genetics, Polymorphism, Single Nucleotide genetics
- Abstract
Background: The SH2B1 gene (Src-homology 2B adaptor protein 1 gene) is a solid candidate gene for obesity. Large scale GWAS studies depicted markers in the vicinity of the gene; animal models suggest a potential relevance for human body weight regulation., Methods: We performed a mutation screen for variants in the SH2B1 coding sequence in 95 extremely obese children and adolescents. Detected variants were genotyped in independent childhood and adult study groups (up to 11,406 obese or overweight individuals and 4,568 controls). Functional implications on STAT3 mediated leptin signalling of the detected variants were analyzed in vitro., Results: We identified two new rare mutations and five known SNPs (rs147094247, rs7498665, rs60604881, rs62037368 and rs62037369) in SH2B1. Mutation g.9483C/T leads to a non-synonymous, non-conservative exchange in the beta (βThr656Ile) and gamma (γPro674Ser) splice variants of SH2B1. It was additionally detected in two of 11,206 (extremely) obese or overweight children, adolescents and adults, but not in 4,506 population-based normal-weight or lean controls. The non-coding mutation g.10182C/A at the 3' end of SH2B1 was only detected in three obese individuals. For the non-synonymous SNP rs7498665 (Thr484Ala) we observed nominal over-transmission of the previously described risk allele in 705 obesity trios (nominal p = 0.009, OR = 1.23) and an increased frequency of the same allele in 359 cases compared to 429 controls (nominal p = 0.042, OR = 1.23). The obesity risk-alleles at Thr484Ala and βThr656Ile/γPro674Ser had no effect on STAT3 mediated leptin receptor signalling in splice variants β and γ., Conclusion: The rare coding mutation βThr656Ile/γPro674Ser (g.9483C/T) in SH2B1 was exclusively detected in overweight or obese individuals. Functional analyzes did not reveal impairments in leptin signalling for the mutated SH2B1.
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- 2012
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35. A genome-wide association meta-analysis identifies new childhood obesity loci.
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Bradfield JP, Taal HR, Timpson NJ, Scherag A, Lecoeur C, Warrington NM, Hypponen E, Holst C, Valcarcel B, Thiering E, Salem RM, Schumacher FR, Cousminer DL, Sleiman PM, Zhao J, Berkowitz RI, Vimaleswaran KS, Jarick I, Pennell CE, Evans DM, St Pourcain B, Berry DJ, Mook-Kanamori DO, Hofman A, Rivadeneira F, Uitterlinden AG, van Duijn CM, van der Valk RJ, de Jongste JC, Postma DS, Boomsma DI, Gauderman WJ, Hassanein MT, Lindgren CM, Mägi R, Boreham CA, Neville CE, Moreno LA, Elliott P, Pouta A, Hartikainen AL, Li M, Raitakari O, Lehtimäki T, Eriksson JG, Palotie A, Dallongeville J, Das S, Deloukas P, McMahon G, Ring SM, Kemp JP, Buxton JL, Blakemore AI, Bustamante M, Guxens M, Hirschhorn JN, Gillman MW, Kreiner-Møller E, Bisgaard H, Gilliland FD, Heinrich J, Wheeler E, Barroso I, O'Rahilly S, Meirhaeghe A, Sørensen TI, Power C, Palmer LJ, Hinney A, Widen E, Farooqi IS, McCarthy MI, Froguel P, Meyre D, Hebebrand J, Jarvelin MR, Jaddoe VW, Smith GD, Hakonarson H, and Grant SF
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- Adolescent, Adult, Body Mass Index, Case-Control Studies, Genetic Predisposition to Disease, Humans, Young Adult, Genetic Loci, Genetic Markers, Genome-Wide Association Study, Obesity genetics, Polymorphism, Single Nucleotide genetics
- Abstract
Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).
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- 2012
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36. Genome-wide association study in German patients with attention deficit/hyperactivity disorder.
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Hinney A, Scherag A, Jarick I, Albayrak Ö, Pütter C, Pechlivanis S, Dauvermann MR, Beck S, Weber H, Scherag S, Nguyen TT, Volckmar AL, Knoll N, Faraone SV, Neale BM, Franke B, Cichon S, Hoffmann P, Nöthen MM, Schreiber S, Jöckel KH, Wichmann HE, Freitag C, Lempp T, Meyer J, Gilsbach S, Herpertz-Dahlmann B, Sinzig J, Lehmkuhl G, Renner TJ, Warnke A, Romanos M, Lesch KP, Reif A, Schimmelmann BG, and Hebebrand J
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- Adolescent, Adult, Child, Female, Genetic Markers, Genotype, Germany, Humans, Male, Receptor, Metabotropic Glutamate 5, Receptors, Metabotropic Glutamate genetics, Attention Deficit Disorder with Hyperactivity genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide
- Abstract
The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome-wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM-IV criteria; Human660W-Quadv1; Illumina, San Diego, CA) and on 1,300 population-based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P-values (best P-value: 8.38 × 10(-7)) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P-values (P-values ≤ 7.57 × 10(-5) ) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect-size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta-analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect-size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome-wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P-values compared to SNPs within random sets of genes of the same size. We did not find genome-wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD., (Copyright © 2011 Wiley Periodicals, Inc.)
- Published
- 2011
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37. Genetic variation of the ghrelin activator gene ghrelin O-acyltransferase (GOAT) is associated with anorexia nervosa.
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Müller TD, Tschöp MH, Jarick I, Ehrlich S, Scherag S, Herpertz-Dahlmann B, Zipfel S, Herzog W, de Zwaan M, Burghardt R, Fleischhaker C, Klampfl K, Wewetzer C, Herpertz S, Zeeck A, Tagay S, Burgmer M, Pfluger PT, Scherag A, Hebebrand J, and Hinney A
- Subjects
- Body Mass Index, Female, Gene Frequency, Genome-Wide Association Study, Genotype, Humans, Male, Odds Ratio, Acyltransferases genetics, Anorexia Nervosa genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics
- Abstract
The gastrointestinal peptide hormone ghrelin promotes food intake and increases body weight and adiposity through activation of the growth hormone secretagogue receptor (GHSR1a). To promote its biological action ghrelin is acylated at its serine 3 residue by the recently discovered ghrelin O-acyltransferase (GOAT, a.k.a. membrane-bound O-acyltransferase 4, MBOAT4). Plasma levels of total and acyl-ghrelin are negatively correlated with body-mass-index (BMI); as lower the BMI as higher plasma levels of total and acylated ghrelin and vice versa. Accordingly, plasma levels of total and acyl-ghrelin are elevated in patients with anorexia nervosa (AN) and decline upon weight regain. The importance of the endogenous Goat/ghrelin system in the neuroendocrine adaptation to fasting was recently highlighted by the observation that acyl-ghrelin mediated elevation of growth hormone (GH) release prevents starvation induced hypoglycemia in Goat(-/-) mice. The aim of this study was to test if genetic variation of GOAT is implicated in the etiology of AN. We therefore assessed association of 6 tagging single nucleotide polymorphisms (tagSNPs), which were predicted to cover 96% the common genetic variability of GOAT plus 50 kb of the 5' and 3' flanking region, in 543 German patients with AN and 612 German normal and underweight healthy controls. Based on a recessive mode of inheritance we observed some evidence for association of the G/G genotype at SNP rs10096097 with AN (nominal two-sided p = 0.031). Based on our results we conclude that genetic variation in GOAT might be implicated in the etiology of AN., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
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- 2011
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38. Novel common copy number variation for early onset extreme obesity on chromosome 11q11 identified by a genome-wide analysis.
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Jarick I, Vogel CI, Scherag S, Schäfer H, Hebebrand J, Hinney A, and Scherag A
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- Adolescent, Adult, Age of Onset, Algorithms, Alleles, Body Mass Index, Child, Female, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Young Adult, Chromosomes, Human, Pair 11 genetics, DNA Copy Number Variations genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Obesity genetics
- Abstract
Heritability of obesity is substantial and recent meta-analyses of genome-wide association studies (GWASs) have been successful in detecting several robustly associated genomic regions for obesity using single-nucleotide polymorphisms (SNPs). However, taken together, the SNPs explain only a small proportion of the overall heritability. Copy number variations (CNVs) might contribute to the 'missing heritability'. We searched genome-wide for association between common CNVs and early-onset extreme obesity. Four hundred and twenty-four case-parents obesity trios and an independent sample of 453 extremely obese children and adolescents and 435 normal-weight and lean adult controls were genotyped by the Affymetrix Genome-Wide Human SNP Array 6.0. We detected 20 common copy number variable regions (CNVRs) which were associated with obesity. The most promising CNVRs were followed-up in an independent sample of 365 obesity trios, confirming the association for two candidate CNVRs. We identified a common CNVR exclusively covering the three olfactory receptor genes OR4P4, OR4S2 and OR4C6 to be associated with obesity (combined P-value = 0.015 in a total of 789 families; odds ratio for the obesity effect allele = 1.19; 95% confidence interval = 1.016-1.394). We also replicated two common deletions (near NEGR1 and at chromosome 10q11.22) that have previously been reported to be associated with body weight. Additionally, we support a rare CNV on chromosome 16 that has recently been reported by two independent groups. However, rare CNVs had not been the focus of our study. We conclude that common CNVs are unlikely to contribute substantially to the genetic basis of early-onset extreme obesity.
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- 2011
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39. Investigation of a genome wide association signal for obesity: synthetic association and haplotype analyses at the melanocortin 4 receptor gene locus.
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Scherag A, Jarick I, Grothe J, Biebermann H, Scherag S, Volckmar AL, Vogel CI, Greene B, Hebebrand J, and Hinney A
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- 3' Flanking Region genetics, 5' Flanking Region genetics, Adolescent, Child, Female, Gene Frequency, Genetic Predisposition to Disease genetics, Genotype, Haplotypes, Humans, Logistic Models, Male, Mutation, Open Reading Frames genetics, Risk Factors, Genome-Wide Association Study methods, Obesity genetics, Polymorphism, Single Nucleotide, Receptor, Melanocortin, Type 4 genetics
- Abstract
Background: Independent genome-wide association studies (GWAS) showed an obesogenic effect of two single nucleotide polymorphisms (SNP; rs12970134 and rs17782313) more than 150 kb downstream of the melanocortin 4 receptor gene (MC4R). It is unclear if the SNPs directly influence MC4R function or expression, or if the SNPs are on a haplotype that predisposes to obesity or includes functionally relevant genetic variation (synthetic association). As both exist, functionally relevant mutations and polymorphisms in the MC4R coding region and a robust association downstream of the gene, MC4R is an ideal model to explore synthetic association., Methodology/principal Findings: We analyzed a genomic region (364.9 kb) encompassing the MC4R in GWAS data of 424 obesity trios (extremely obese child/adolescent and both parents). SNP rs12970134 showed the lowest p-value (p = 0.004; relative risk for the obesity effect allele: 1.37); conditional analyses on this SNP revealed that 7 of 78 analyzed SNPs provided independent signals (p≤0.05). These 8 SNPs were used to derive two-marker haplotypes. The three best (according to p-value) haplotype combinations were chosen for confirmation in 363 independent obesity trios. The confirmed obesity effect haplotype includes SNPs 3' and 5' of the MC4R. Including MC4R coding variants in a joint model had almost no impact on the effect size estimators expected under synthetic association., Conclusions/significance: A haplotype reaching from a region 5' of the MC4R to a region at least 150 kb from the 3' end of the gene showed a stronger association to obesity than single SNPs. Synthetic association analyses revealed that MC4R coding variants had almost no impact on the association signal. Carriers of the haplotype should be enriched for relevant mutations outside the MC4R coding region and could thus be used for re-sequencing approaches. Our data also underscore the problems underlying the identification of relevant mutations depicted by GWAS derived SNPs.
- Published
- 2010
- Full Text
- View/download PDF
40. 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
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Scherag A, Dina C, Hinney A, Vatin V, Scherag S, Vogel CI, Müller TD, Grallert H, Wichmann HE, Balkau B, Heude B, Jarvelin MR, Hartikainen AL, Levy-Marchal C, Weill J, Delplanque J, Körner A, Kiess W, Kovacs P, Rayner NW, Prokopenko I, McCarthy MI, Schäfer H, Jarick I, Boeing H, Fisher E, Reinehr T, Heinrich J, Rzehak P, Berdel D, Borte M, Biebermann H, Krude H, Rosskopf D, Rimmbach C, Rief W, Fromme T, Klingenspor M, Schürmann A, Schulz N, Nöthen MM, Mühleisen TW, Erbel R, Jöckel KH, Moebus S, Boes T, Illig T, Froguel P, Hebebrand J, and Meyre D
- Subjects
- Adolescent, Adult, Age of Onset, Alleles, Body Mass Index, Child, France epidemiology, Genetic Predisposition to Disease, Genome-Wide Association Study, Germany epidemiology, Humans, Obesity epidemiology, Polymorphism, Single Nucleotide, Body Weight genetics, Genetic Loci, Genome, Human, Obesity genetics
- Abstract
Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85x10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84x10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at approximately 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2010
- Full Text
- View/download PDF
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