21 results on '"Groop, L.C."'
Search Results
2. Correction: The influence of age and sex on genetic associations with adult body size and shape : a large-scale genome-wide interaction study.
- Author
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Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der Most, P.J., Völker, U., Vohl, M.C., Vonk, J.M., Waldenberger, M., Walker, R.W., Wennauer, R., Widén, E., Willemsen, G., Wilsgaard, T., Wright, A.F., Zillikens, M.C., van Dijk, S.C., van Schoor, N.M., Asselbergs, F.W., de Bakker, P.I., Beckmann, J.S., Beilby, J., Bennett, D.A., Bergman, R.N., Bergmann, S., Böger, C.A., Boehm, B.O., Boerwinkle, E., Boomsma, D.I., Bornstein, S.R., Bottinger, E.P., Bouchard, C., Chambers, J.C., Chanock, S.J., Chasman, D.I., Cucca, F., Cusi, D., Dedoussis, G., Erdmann, J., Eriksson, J.G., Evans, D.A., de Faire, U., Farrall, M., Ferrucci, L., Ford, I., Franke, L., Franks, P.W., Froguel, P., Gansevoort, R.T., Gieger, C., Grönberg, H., Gudnason, V., Gyllensten, U., Hall, P., Hamsten, A., van der Harst, P., Hayward, C., Heliövaara, M., Hengstenberg, C., Hicks, A.A., Hingorani, A., Hofman, A., Hu, F., Huikuri, H.V., Hveem, K., James, A.L., Jordan, J.M., Jula, A., Kähönen, M., Kajantie, E., Kathiresan, S., Kiemeney, L.A., Kivimaki, M., Knekt, P.B., Koistinen, H.A., Kooner, J.S., Koskinen, S., Kuusisto, J., Maerz, W., Martin, N.G., Laakso, M., Lakka, T.A., Lehtimäki, T., Lettre, G., Levinson, D.F., Lind, L., Lokki, M.L., Mäntyselkä, P., Melbye, M., Metspalu, A., Mitchell, B.D., Moll, F.L., Murray, J.C., Musk, A.W., Nieminen, M.S., Njølstad, I., Ohlsson, C., Oldehinkel, A.J., Oostra, B.A., Palmer, L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., Loos, R.J., Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der Most, P.J., Völker, U., Vohl, M.C., Vonk, J.M., Waldenberger, M., Walker, R.W., Wennauer, R., Widén, E., Willemsen, G., Wilsgaard, T., Wright, A.F., Zillikens, M.C., van Dijk, S.C., van Schoor, N.M., Asselbergs, F.W., de Bakker, P.I., Beckmann, J.S., Beilby, J., Bennett, D.A., Bergman, R.N., Bergmann, S., Böger, C.A., Boehm, B.O., Boerwinkle, E., Boomsma, D.I., Bornstein, S.R., Bottinger, E.P., Bouchard, C., Chambers, J.C., Chanock, S.J., Chasman, D.I., Cucca, F., Cusi, D., Dedoussis, G., Erdmann, J., Eriksson, J.G., Evans, D.A., de Faire, U., Farrall, M., Ferrucci, L., Ford, I., Franke, L., Franks, P.W., Froguel, P., Gansevoort, R.T., Gieger, C., Grönberg, H., Gudnason, V., Gyllensten, U., Hall, P., Hamsten, A., van der Harst, P., Hayward, C., Heliövaara, M., Hengstenberg, C., Hicks, A.A., Hingorani, A., Hofman, A., Hu, F., Huikuri, H.V., Hveem, K., James, A.L., Jordan, J.M., Jula, A., Kähönen, M., Kajantie, E., Kathiresan, S., Kiemeney, L.A., Kivimaki, M., Knekt, P.B., Koistinen, H.A., Kooner, J.S., Koskinen, S., Kuusisto, J., Maerz, W., Martin, N.G., Laakso, M., Lakka, T.A., Lehtimäki, T., Lettre, G., Levinson, D.F., Lind, L., Lokki, M.L., Mäntyselkä, P., Melbye, M., Metspalu, A., Mitchell, B.D., Moll, F.L., Murray, J.C., Musk, A.W., Nieminen, M.S., Njølstad, I., Ohlsson, C., Oldehinkel, A.J., Oostra, B.A., Palmer, L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., and Loos, R.J.
- Abstract
This corrects the article DOI: 10.1371/journal.pgen.1005378.
- Published
- 2016
3. SR-B1 variants associated with HDL cholesterol levels in three populations
- Author
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McCarthy, J.J., Lewitzky, S., Permutt, A., Glaser, B., Groop, L.C., and Meyer, J.
- Subjects
Human genetics -- Research ,Human chromosome abnormalities -- Research ,Genetic disorders -- Research ,Lipid research -- Reports ,Lipids -- Physiological aspects ,Cholesterol, HDL -- Physiological aspects ,Genetic polymorphisms -- Physiological aspects ,Type 2 diabetes -- Genetic aspects ,Biological sciences - Published
- 2001
4. Gene expression profiling in skeletal muscle of subjects with different glycaemic tolerance
- Author
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Lindgren, C.M., Lehar, J., Hirschhorn, J., Vaag, A., Poulssen, P., Eriksson, K.F., Gaasenbeek, M., Ladd, C., Tamayo, P., Daly, M.J., Ridderstrale, M., Beck-Nielsen, H., Lander, E.S., Altshuler, D., and Groop, L.C.
- Subjects
Human genetics -- Research ,Genetic disorders -- Research ,Type 2 diabetes -- Genetic aspects ,Striated muscle -- Physiological aspects ,Biological sciences - Published
- 2001
5. Linkage disequilibrium at PPARG and other genes assessed with dense sets of SNPs
- Author
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Hirschhorn, J.N., Altshuler, D., Daly, M.J., Lindgren, C.M., Burtt, N.P., Loomer, M., Villapakkam, A., Bolk, S., O'Donnell, C.J., Crews, J.D., Groop, L.C., and Lander, E.S.
- Subjects
Linkage (Genetics) -- Research ,Genetic polymorphisms -- Research ,Genetic disorders -- Research ,Biological sciences - Published
- 2001
6. New genetic loci link adipose and insulin biology to body fat distribution.
- Author
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ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., Carlson, OD., Egan, JM., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, ML., Loo, BM., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, HE., Deloukas, P., Katsareli, E., Couper, DJ., Duncan, BB., Kloppenburg, M., Adair, LS., Borja, JB., Wilson, JG., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, TM., Allison, MA., Redline, S., Buxbaum, SG., Mohlke, KL., Meulenbelt, I., Ballantyne, CM., Dedoussis, GV., Hu, FB., Liu, Y., Paulweber, B., Spector, TD., Slagboom, P., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, JC., Salomaa, V., Eriksson, JG., Frayling, TM., Hicks, AA., Lehtimäki, T., Smith, GD., Siscovick, DS., Kronenberg, F., van Duijn, C., Loos, RJ., Waterworth, DM., Meigs, JB., Dupuis, J., Richards, JB., Willenborg, C., Farrall, M., Assimes, TL., Thompson, JR., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, BA., Stirrups, K., König, IR., Cazier, JB., Johansson£££Åsa£££ Å., Hall, AS., Lee, JY., Willer, CJ., Chambers, JC., 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Bouatia-Naji, N., Ahmadi, KR., Ainali, C., Barrett, A., Bataille, V., Bell, JT., Buil, A., Dermitzakis, ET., Dimas, AS., Durbin, R., Glass, D., Hassanali, N., Hedman£££Åsa K£££ ÅK., Ingle, C., Keildson, S., Knowles, D., Krestyaninova, M., Lowe, CE., Meduri, E., di Meglio, P., Min, JL., Montgomery, SB., Nestle, FO., Nica, AC., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, SY., Small, KS., Surdulescu, G., Travers, ME., Tsaprouni, L., Tsoka, S., Wilk, A., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., Heiss, G., Taylor, K., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Crawford, D., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Ritchie, M., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Peters, U., Anderson, G., Carlson, C., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, W., Albrecht, E., Alizadeh, BZ., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Keyzer, J., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Winkler, T.W., Croteau-Chonka, D.C., Locke, A.E., Strawbridge, R.J., Pers, T.H., Justice, A.E., Workalemahu, T., Wu, J.M., Buchkovich, M.L., Heard-Costa, N.L., Roman, T.S., Drong, A.W., Day, F.R., Luan, J., Randall, J.C., Scherag, A., Wood, A.R., Fehrmann, R., Karjalainen, J., Kahali, B., Liu, C.T., Schmidt, E.M., Anderson, D., Bragg-Gresham, J.L., Ehret, G.B., Feitosa, M.F., Jackson, A.U., Kleber, M.E., Mateo Leach, I., Medina-Gomez, C., Palmer, C.D., Pasko, D., Pechlivanis, S., Peters, M.J., Ju Sung, Y., Van Vliet-Ostaptchouk, J.V., Yengo, L., Arscott, G.M., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bonnet, F., Böttcher, Y., Carba, D.B., Caspersen, I.H., Daw, E.W., Deelen, J., Delgado, G., Doney, A.S., Eklund, N., Erdos, M.R., Eury, E., Friedrich, N., Garcia, M.E., Giedraitis, V., Go, A.S., Golay, A., Grammer, T.B., Gräßler, J., Grewal, J., Groves, C.J., Hartman, C.A., Hassinen, M., Herzig, K.H., Helmer, Q., Hillege, H.L., Holmen, O., Hunt, S.C., Ittermann, T., James, A.L., Johansson, I., Juliusdottir, T., Kalafati, I.P., Kinnunen, L., Kooner, I.K., Lee, N.R., Lichtner, P., Lobbens, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Mills, R., Monda, K.L., Mooijaart, S.P., Mühleisen, T.W., Mulas, A., Nalls, M.A., Glorioso, N., Nolte, I.M., Rayner, N.W., Renstrom, F., Ried, J.S., Robertson, N.R., Rose, L.M., Scholtens, S., Seufferlein, T., Sitlani, C.M., Vernon Smith, A., Stringham, H.M., Sundström, J., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tayo, B.O., Tomaschitz, A., Troffa, C., van Oort, F.V., Vonk, J.M., Waite, L.L., Wennauer, R., Wojczynski, M.K., Zhang, Q., Hua Zhao, J., Brennan, E.P., Choi, M., Gharavi, A.G., Hedman, Å.K., Hivert, M.F., Huang, J., Karpe, F., Kiryluk, K., Liang, L., Lifton, R.P., Ma, B., McKnight, A.J., McPherson, R., Min, J.L., Moffatt, M.F., Montgomery, G.W., Murabito, J.M., Nicholson, G., Nyholt, D.R., Olsson, C., Perry, J.R., Reinmaa, E., Salem, R.M., Schadt, E.E., Scott, R.A., Vallejo, E.E., Westra, H.J., Zondervan, K.T., Bakker, S.J., Beilby, J., Bergman, R.N., Blangero, J., Brown, M.J., Chines, P.S., Collins, F.S., Crawford, D.C., de Geus, E.J., Erbel, R., Eriksson, J.G., Ferrannini, E., Forouhi, N.G., Franco, O.H., Gansevoort, R.T., Haiman, C.A., Harris, T.B., Hattersley, A.T., Heliövaara, M., Hicks, A.A., Hingorani, A.D., Hoffmann, W., Humphries, S.E., Jarvelin, M.R., Johansen, B., Jousilahti, P., Jula, A.M., Keinanen-Kiukaanniemi, S.M., Kooner, J.S., Kraja, A.T., Lakka, T.A., Le Marchand, L., Lyssenko, V., Männistö, S., Marette, A., Matise, T.C., McKenzie, C.A., Musk, A.W., Möhlenkamp, S., Morris, A.D., Oldehinkel, A.J., Ong, K.K., Palmer, L.J., Penninx, B.W., Pramstaller, P.P., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Ridker, P.M., Ritchie, M.D., Samani, N.J., Sarzynski, M.A., Schwarz, P.E., Shuldiner, A.R., Staessen, J.A., Steinthorsdottir, V., Stolk, R.P., Strauch, K., Tremblay, A., Vohl, M.C., Wilson, J.F., Witteman, J.C., Adair, L.S., Boehm, B.O., Bornstein, S.R., Bouchard, C., Cauchi, S., Caulfield, M.J., Chambers, J.C., Chasman, D.I., Cooper, R.S., Grabe, H.J., Jöckel, K.H., Munroe, P.B., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Pérusse, L., Saaristo, T.E., Slagboom, P.E., Spector, T.D., Uitterlinden, A.G., Veronesi, G., Walker, M., Wareham, N.J., Wichmann, H.E., Abecasis, G.R., Assimes, T.L., Berndt, S.I., Borecki, I.B., Frayling, T.M., Groop, L.C., Hunter, D.J., Kaplan, R.C., O'Connell, J.R., Strachan, D.P., van Duijn, C.M., Willer, C.J., Visscher, P.M., Yang, J., Hirschhorn, J.N., Zillikens, M.C., McCarthy, M.I., Speliotes, E.K., North, K.E., Fox, C.S., Franks, P.W., Heid, I.M., Loos, R.J., Cupples, L.A., Morris, A.P., Lindgren, C.M., and Mohlke, K.L.
- Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
- Published
- 2015
7. Sex-stratified Genome-wide Association Studies Including 270000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits
- Author
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Randall, J.C., Winkler, T.W., Kutalik, Z., Berndt, S.I., Jackson, A.U., Monda, K.L., Kilpeläinen, T.O., Esko, T., Mägi, R., Li, S., Workalemahu, T., Feitosa, M.F., Croteau-Chonka, D.C., Day, F.R., Fall, T., Ferreira, T., Gustafsson, S., Locke, A.E., Mathieson, I., Scherag, A., Vedantam, S., Wood, A.R., Liang, L., Steinthorsdottir, V., Thorleifsson, G., Dermitzakis, E.T., Dimas, A.S., Karpe, F., Min, J.L., Nicholson, G., Clegg, D.J., Person, T., Krohn, J.P., Bauer, S., Buechler, C., Eisinger, K., Bonnefond, A., Froguel, P., Hottenga, J.J., Prokopenko, I., Waite, L.L., Harris, T.B., Smith, A.V., Shuldiner, A.R., McArdle, W.L., Caulfield, M.J., Munroe, P.B., Grönberg, H., Chen, Y.D., Li, G., Beckmann, J.S., Johnson, T., Thorsteinsdottir, U., Teder-Laving, M., Khaw, K.T., Wareham, N.J., Zhao, J.H., Amin, N., Oostra, B.A., Kraja, A.T., Province, M.A., Cupples, L.A., Heard-Costa, N.L., Kaprio, J., Ripatti, S., Surakka, I., Collins, F.S., Saramies, J., Tuomilehto, J., Jula, A., Salomaa, V., Erdmann, J., Hengstenberg, C., Loley, C., Schunkert, H., Lamina, C., Wichmann, H.E., Albrecht, E., Gieger, C., Hicks, A.A., Johansson, A., Pramstaller, P.P., Kathiresan, S., Speliotes, E.K., Penninx, B.W.J.H., Hartikainen, A.L., Järvelin, M.R., Gyllensten, U., Boomsma, D.I., Campbell, H., Wilson, J.F., Chanock, S.J., Farrall, M., Goel, A., Medina-Gomez, C., Rivadeneira, F., Estrada, K., Uitterlinden, A.G., Hofman, A., Zillikens, M.C., den Heijer, M., Kiemeney, L.A., Maschio, A., Hall, P., Tyrer, J., Teumer, A., Völzke, H., Kovacs, P., Tönjes, A., Mangino, M., Spector, T.D., Hayward, C., Rudan, I., Hall, A.S., Samani, N.J., Attwood, A.P., Sambrook, J.G., Hung, J., Palmer, L.J., Lokki, M.L., Sinisalo, J., Boucher, G., Huikuri, H.V., Lorentzon, M., Ohlsson, C., Eklund, N., Eriksson, J.G., Barlassina, C., Rivolta, C., Nolte, I.M., Snieder, H., van der Klauw, M.M., van Vliet-Ostaptchouk, J.V., Gejman, P.V., Shi, J., Jacobs, K.B., Wang, Z., Bakker, S.J., Mateo Leach, I., Navis, G., van der Harst, P., Martin, N.G., Medland, S.E., Montgomery, G.W., Yang, J., Chasman, D.I., Ridker, P.M., Rose, L.M., Lehtimäki, T., Raitakari, O., Absher, D., Iribarren, C., Basart, H., Hovingh, K.G., Hyppönen, E., Power, C., Anderson, D., Beilby, J.P., Hui, J., Jolley, J., Sager, H., Bornstein, S.R., Schwarz, P.E., Kristiansson, K., Perola, M., Lindström, J., Swift, A.J., Uusitupa, M., Atalay, M., Lakka, T.A., Rauramaa, R., Bolton, J.L., Fowkes, G., Fraser, R.M., Price, J.F., Fischer, K., Krjuta Kov, K., Metspalu, A., Mihailov, E., Langenberg, C., Luan, J., Ong, K.K., Chines, P.S., Keinanen-Kiukaanniemie, S., Saaristo, T.E., Edkins, S., Franks, P.W., Hallmans, G., Shungin, D., Morris, A.D., Palmer, C.N.A., Erbel, R., Moebus, S., Nöthen, M.M., Pechlivanis, S., Hveem, K., Narisu, N., Hamsten, A., Humphries, S.E., Strawbridge, R.J., Tremoli, E., Grallert, H., Thorand, B., Illig, T., Koenig, W., Müller-Nurasyid, M., Peters, A., Boehm, B.O., Kleber, M.E., März, W., Winkelmann, B.R., Kuusisto, J., Laakso, M., Arveiler, D., Cesana, G., Kuulasmaa, K., Virtamo, J., Yarnell, J.W., Kuh, D, Wong, A., Lind, L., de Faire, U., Gigante, B., Magnusson, P.K.E., Pedersen, N.L., Dedoussis, G., Dimitriou, M., Kolovou, G., Kanoni, S., Stirrups, K., Bonnycastle, L.L., Njolstad, I., Wilsgaard, T., Ganna, A., Rehnberg, E., Hingorani, A.D., Kivimaki, M., Kumari, M., Assimes, T.L., Barroso, I., Boehnke, M., Borecki, I.B., Deloukas, P., Fox, C.S., Frayling, T.M., Groop, L.C., Haritunians, T., Hunter, D., Ingelsson, E., Kaplan, R., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Abecasis, G.R., McCarthy, M.I., Hirschhorn, J.N., Qi, L., Loos, R.J., Lindgren, C.M., North, K.E., Heid, I.M., Psychiatry, Internal medicine, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Lifestyle, overweight and diabetes, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, and Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease
- Subjects
Netherlands Twin Register (NTR) ,SDG 3 - Good Health and Well-being ,SDG 5 - Gender Equality - Abstract
Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR
- Published
- 2013
- Full Text
- View/download PDF
8. Defining the role of common variation in the genomic and biological architecture of adult human height.
- Author
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Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., 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Z., Yengo, L., Zhang, W., Afzal, U., Arnlöv, J., Arscott, G.M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bolton, J.L., Böttcher, Y., Boyd, H.A., Buckley, B.M., Caspersen, I.H., Chines, P.S., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, E.W., De Jong, P.A., Deelen, J., Delgado, G., Denny, J.C., Dhonukshe-Rutten, R., Dimitriou, M., Doney, A.S., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, M.E., Geller, F., Giedraitis, V., Go, A.S., Grallert, H., Grammer, T.B., Gräßler, J., Grönberg, H., de Groot, L.C., Groves, C.J., Hall, P., Haller, T., Hallmans, G., Hannemann, A., Hartman, C.A., Hassinen, M., Hayward, C., Heard-Costa, N.L., Helmer, Q., Hemani, G., Henders, A.K., Hillege, H.L., Hlatky, M.A., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, J.J., Illig, T., Isaacs, A., James, A.L., Johansen, B., Johansson, Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, A.N., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, P.K., Mahajan, A., Maillard, M., McArdle, W.L., McKenzie, C.A., McLachlan, S., McLaren, P.J., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, K.L., Morken, M.A., Müller, G., Müller-Nurasyid, M., Musk, A.W., Narisu, N., Nauck, M., Nolte, I.M., Nöthen, M.M., Oozageer, L., Pilz, S., Rayner, N.W., Renstrom, F., Robertson, N.R., Rose, L.M., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F.R., Scott, R.A., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, J.H., Smith, A.V., Smolonska, J., Stanton, A.V., Stirrups, K., Stott, D.J., Stringham, H.M., Sundström, J., Swertz, M.A., Syvänen, A.C., Tayo, B.O., Tyrer, J.P., van Dijk, S., van Schoor, N.M., van der Velde, N., van Heemst, D., van Oort, F.V., Vermeulen, S.H., Verweij, N., Vonk, J.M., Waite, L.L., Waldenberger, M., Wennauer, R., Wilkens, L.R., Willenborg, C., Wilsgaard, T., Wojczynski, M.K., Wong, A., Wright, A.F., 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Laakso, M., Liu, Y., Martin, N.G., März, W., Melbye, M., Moebus, S., Munroe, P.B., Njølstad, I., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Perola, M., Pérusse, L., Powell, J.E., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, P.M., Rivadeneira, F., Rotter, J.I., Saaristo, T.E., Saleheen, D., Schlessinger, D., Slagboom, P.E., Spector, T.D., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., Völzke, H., Walker, M., Wareham, N.J., Watkins, H., Wichmann, H.E., Wilson, J.F., Zanen, P., Heid, I.M., Lindgren, C.M., Mohlke, K.L., Speliotes, E.K., Barroso, I., Fox, C.S., North, K.E., Strachan, D.P., Beckmann, J.S., Berndt, S.I., Boehnke, M., Borecki, I.B., McCarthy, M.I., Metspalu, A., Uitterlinden, A.G., van Duijn, C.M., Willer, C.J., Price, A.L., Lettre, G., Loos, R.J., Weedon, M.N., Ingelsson, E., O'Connell, J.R., Abecasis, G.R., Chasman, D.I., Goddard, M.E., Visscher, P.M., Hirschhorn, J.N., Frayling, T.M., Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE 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HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Wood, A.R., Esko, T., Yang, J., Vedantam, S., Pers, T.H., Gustafsson, S., Chu, A.Y., Estrada, K., Luan, J., Kutalik, Z., Amin, N., Buchkovich, M.L., Croteau-Chonka, D.C., Day, F.R., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, A.U., Karjalainen, J., Lo, K.S., Locke, A.E., Mägi, R., Mihailov, E., Porcu, E., Randall, J.C., Scherag, A., Vinkhuyzen, A.A., Westra, H.J., Winkler, T.W., Workalemahu, T., Zhao, J.H., Absher, D., Albrecht, E., Anderson, D., Baron, J., Beekman, M., Demirkan, A., Ehret, G.B., Feenstra, B., Feitosa, M.F., Fischer, K., Fraser, R.M., Goel, A., Justice, A.E., Kanoni, S., Kleber, M.E., Kristiansson, K., Lotay, V., Lui, J.C., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Nalls, M.A., Nyholt, D.R., Palmer, C.D., Pasko, D., Pechlivanis, S., Prokopenko, I., Ried, J.S., Ripke, S., Shungin, D., Stancáková, A., Strawbridge, R.J., Sung, Y.J., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S.W., van Setten, J., Van Vliet-Ostaptchouk, J.V., Wang, Z., Yengo, L., Zhang, W., Afzal, U., Arnlöv, J., Arscott, G.M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bolton, J.L., Böttcher, Y., Boyd, H.A., Buckley, B.M., Caspersen, I.H., Chines, P.S., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, E.W., De Jong, P.A., Deelen, J., Delgado, G., Denny, J.C., Dhonukshe-Rutten, R., Dimitriou, M., Doney, A.S., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, M.E., Geller, F., Giedraitis, V., Go, A.S., Grallert, H., Grammer, T.B., Gräßler, J., Grönberg, H., de Groot, L.C., Groves, C.J., Hall, P., Haller, T., Hallmans, G., Hannemann, A., Hartman, C.A., Hassinen, M., Hayward, C., Heard-Costa, N.L., Helmer, Q., Hemani, G., Henders, A.K., Hillege, H.L., Hlatky, M.A., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, J.J., Illig, T., Isaacs, A., James, A.L., Johansen, B., Johansson, Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, A.N., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, P.K., Mahajan, A., Maillard, M., McArdle, W.L., McKenzie, C.A., McLachlan, S., McLaren, P.J., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, K.L., Morken, M.A., Müller, G., Müller-Nurasyid, M., Musk, A.W., Narisu, N., Nauck, M., Nolte, I.M., Nöthen, M.M., Oozageer, L., Pilz, S., Rayner, N.W., Renstrom, F., Robertson, N.R., Rose, L.M., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F.R., Scott, R.A., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, J.H., Smith, A.V., Smolonska, J., Stanton, A.V., Stirrups, K., Stott, D.J., Stringham, H.M., Sundström, J., Swertz, M.A., Syvänen, A.C., Tayo, B.O., Tyrer, J.P., van Dijk, S., van Schoor, N.M., van der Velde, N., van Heemst, D., van Oort, F.V., Vermeulen, S.H., Verweij, N., Vonk, J.M., Waite, L.L., Waldenberger, M., Wennauer, R., Wilkens, L.R., Willenborg, C., Wilsgaard, T., Wojczynski, M.K., Wong, A., Wright, A.F., Zhang, Q., Arveiler, D., Bakker, S.J., Beilby, J., Bergman, 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Moebus, S., Munroe, P.B., Njølstad, I., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Perola, M., Pérusse, L., Powell, J.E., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, P.M., Rivadeneira, F., Rotter, J.I., Saaristo, T.E., Saleheen, D., Schlessinger, D., Slagboom, P.E., Spector, T.D., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., Völzke, H., Walker, M., Wareham, N.J., Watkins, H., Wichmann, H.E., Wilson, J.F., Zanen, P., Heid, I.M., Lindgren, C.M., Mohlke, K.L., Speliotes, E.K., Barroso, I., Fox, C.S., North, K.E., Strachan, D.P., Beckmann, J.S., Berndt, S.I., Boehnke, M., Borecki, I.B., McCarthy, M.I., Metspalu, A., Uitterlinden, A.G., van Duijn, C.M., Willer, C.J., Price, A.L., Lettre, G., Loos, R.J., Weedon, M.N., Ingelsson, E., O'Connell, J.R., Abecasis, G.R., Chasman, D.I., Goddard, M.E., Visscher, P.M., Hirschhorn, J.N., and Frayling, T.M.
- Abstract
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
- Published
- 2014
9. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
- Author
-
DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., O'Leary, DH., Dastani, Z., Hivert, M.F., Timpson, N., Perry, J.R., Yuan, X., Scott, R.A., Henneman, P., Heid, I.M., Kizer, J.R., Lyytikäinen, L.P., Fuchsberger, C., Tanaka, T., Morris, A.P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, J.S., Uh, H.W., Wu, Y., Bidulescu, A., Rasmussen-Torvik, L.J., Greenwood, C.M., Ladouceur, M., Grimsby, J., Manning, A.K., Liu, C.T., Kooner, J., Mooser, V.E., Vollenweider, P., Kapur, K.A., Chambers, J., Wareham, N.J., Langenberg, C., Frants, R., Willems-Vandijk, K., Oostra, B.A., Willems, S.M., Lamina, C., Winkler, T.W., Psaty, B.M., Tracy, R.P., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, P.P., Evans, D.M., St Pourcain, B., Sattar, N., Wood, A.R., Bandinelli, S., Carlson, O.D., Egan, J.M., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, M.L., Loo, B.M., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, H.E., Deloukas, P., Katsareli, E., Couper, D.J., Duncan, B.B., Kloppenburg, M., Adair, L.S., Borja, J.B., Wilson, J.G., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, T.M., Allison, M.A., Redline, S., Buxbaum, S.G., Mohlke, K.L., Meulenbelt, I., Ballantyne, C.M., Dedoussis, G.V., Hu, F.B., Liu, Y., Paulweber, B., Spector, T.D., Slagboom, P.E., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, J.C., Salomaa, V., Eriksson, J.G., Frayling, T.M., Hicks, A.A., Lehtimäki, T., Smith, G.D., Siscovick, D.S., Kronenberg, F., van Duijn, C., Loos, R.J., Waterworth, D.M., Meigs, J.B., Dupuis, J., Richards, J.B., Voight, B.F., Scott, L.J., Steinthorsdottir, V., 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., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Hassanali, N., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lindgren, C.M., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., 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., Morris, A.D., Palmer, C.N., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Pedersen, O., 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., Soranzo, N., Wheeler, E., Glazer, N.L., Bouatia-Naji, N., Mägi, R., Randall, J., Elliott, P., Rybin, D., Dehghan, A., Hottenga, J.J., Song, K., Goel, A., Lajunen, T., Doney, A., Cavalcanti-Proença, C., Kumari, M., Timpson, N.J., Zabena, C., Ingelsson, E., An, P., O'Connell, J., Luan, J., Elliott, A., Roccasecca, R.M., Pattou, F., Sethupathy, P., Ariyurek, Y., Barter, P., Beilby, J.P., Ben-Shlomo, Y., Bergmann, S., Bochud, M., Bonnefond, A., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, S.J., Chen, Y.D., Chines, P., Clarke, R., Coin, L.J., Cooper, M.N., Crisponi, L., Day, I.N., de Geus, E.J., Delplanque, J., Fedson, A.C., Fischer-Rosinsky, A., Forouhi, N.G., Franzosi, M.G., Galan, P., Goodarzi, M.O., Graessler, J., Grundy, S., Gwilliam, R., Hallmans, G., Hammond, N., Han, X., Hartikainen, A.L., Hayward, C., Heath, S.C., Hercberg, S., Hillman, D.R., Hingorani, A.D., Hui, J., Hung, J., Kaakinen, M., Kaprio, J., Kesaniemi, Y.A., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, K.O., Lathrop, G.M., Lawlor, D.A., Le Bacquer, O., Lecoeur, C., Li, Y., Mahley, R., Mangino, M., Martínez-Larrad, M.T., McAteer, J.B., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, B.D., Mukherjee, S., Naitza, S., Neville, M.J., Orrù, M., Pakyz, R., Paolisso, G., Pattaro, C., Pearson, D., Peden, J.F., Pedersen, N.L., Pfeiffer, A.F., Pichler, I., Polasek, O., Posthuma, D., Potter, S.C., Pouta, A., Province, M.A., Rice, K., Ripatti, S., Rivadeneira, F., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, A.A., Scheet, P., Seedorf, U., Sharp, S.J., Shields, B., Sigurðsson, G., Sijbrands, E.J., Silveira, A., Simpson, L., Singleton, A., Smith, N.L., Sovio, U., Swift, A., Syddall, H., Syvänen, A.C., Tönjes, A., Uitterlinden, A.G., van Dijk, K.W., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, P.J., Walley, A., Ward, K.L., Watkins, H., Wild, S.H., Willemsen, G., Witteman, J.C., Yarnell, J.W., Zelenika, D., Zethelius, B., Zhai, G., Zhao, J.H., Zillikens, M.C., Borecki, I.B., Meneton, P., Magnusson, P.K., Nathan, D.M., Williams, G.H., Silander, K., Bornstein, S.R., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, A.R., Cooper, C., Serrano-Ríos, M., Lind, L., Palmer, L.J., Franks, P.W., Ebrahim, S., Marmot, M., Wright, A.F., Stumvoll, M., Hamsten, A., Buchanan, T.A., Valle, T.T., Rotter, J.I., Penninx, B.W., Boomsma, D.I., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, M.R., Peltonen, L., Mooser, V., Musunuru, K., Smith, A.V., Edmondson, A.C., Stylianou, I.M., Koseki, M., Pirruccello, J.P., Chasman, D.I., Johansen, C.T., Fouchier, S.W., Peloso, G.M., Barbalic, M., Ricketts, S.L., Bis, J.C., Feitosa, M.F., Orho-Melander, M., Melander, O., Li, X., Cho, Y.S., Go, M.J., Kim, Y.J., Lee, J.Y., Park, T., Kim, K., Sim, X., Ong, R.T., Croteau-Chonka, D.C., Lange, L.A., Smith, J.D., Ziegler, A., Zhang, W., Zee, R.Y., Whitfield, J.B., Thompson, J.R., Surakka, I., Smit, J.H., Sinisalo, J., Scott, J., Saharinen, J., Sabatti, C., Rose, L.M., Roberts, R., Rieder, M., Parker, A.N., Pare, G., O'Donnell, C.J., Nieminen, M.S., Nickerson, D.A., Montgomery, G.W., McArdle, W., Masson, D., Martin, N.G., Marroni, F., Lucas, G., Luben, R., Lokki, M.L., Lettre, G., Launer, L.J., Lakatta, E.G., Laaksonen, R., König, I.R., Khaw, K.T., Kaplan, L.M., Johansson, Å., Janssens, A.C., Igl, W., Hovingh, G.K., Hengstenberg, C., Havulinna, A.S., Hastie, N.D., Harris, T.B., Haritunians, T., Hall, A.S., Groop, L.C., Gonzalez, E., Freimer, N.B., Erdmann, J., Ejebe, K.G., Döring, A., Dominiczak, A.F., Demissie, S., de Faire, U., Caulfield, M.J., Boekholdt, S.M., Assimes, T.L., Quertermous, T., Seielstad, M., Wong, T.Y., Tai, E.S., Feranil, A.B., Kuzawa, C.W., Taylor, H.A., Gabriel, S.B., Holm, H., Gudnason, V., Krauss, R.M., Ordovas, J.M., Munroe, P.B., Kooner, J.S., Tall, A.R., Hegele, R.A., Kastelein, J.J., Schadt, E.E., Strachan, D.P., Reilly, M.P., Samani, N.J., Schunkert, H., Cupples, L.A., Sandhu, M.S., Ridker, P.M., Rader, D.J., Kathiresan, S., DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., O'Leary, DH., Dastani, Z., Hivert, M.F., Timpson, N., Perry, J.R., Yuan, X., Scott, R.A., Henneman, P., Heid, I.M., Kizer, J.R., Lyytikäinen, L.P., Fuchsberger, C., Tanaka, T., Morris, A.P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, J.S., Uh, H.W., Wu, Y., Bidulescu, A., Rasmussen-Torvik, L.J., Greenwood, C.M., Ladouceur, M., Grimsby, J., Manning, A.K., Liu, C.T., Kooner, J., Mooser, V.E., Vollenweider, P., Kapur, K.A., Chambers, J., Wareham, N.J., Langenberg, C., Frants, R., Willems-Vandijk, K., Oostra, B.A., Willems, S.M., Lamina, C., Winkler, T.W., Psaty, B.M., Tracy, R.P., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, P.P., Evans, D.M., St Pourcain, B., Sattar, N., Wood, A.R., Bandinelli, S., Carlson, O.D., Egan, J.M., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, M.L., Loo, B.M., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, H.E., Deloukas, P., Katsareli, E., Couper, D.J., Duncan, B.B., Kloppenburg, M., Adair, L.S., Borja, J.B., Wilson, J.G., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, T.M., Allison, M.A., Redline, S., Buxbaum, S.G., Mohlke, K.L., Meulenbelt, I., Ballantyne, C.M., Dedoussis, G.V., Hu, F.B., Liu, Y., Paulweber, B., Spector, T.D., Slagboom, P.E., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, J.C., Salomaa, V., Eriksson, J.G., Frayling, T.M., Hicks, A.A., Lehtimäki, T., Smith, G.D., Siscovick, D.S., Kronenberg, F., van Duijn, C., Loos, R.J., Waterworth, D.M., Meigs, J.B., Dupuis, J., Richards, J.B., Voight, B.F., Scott, L.J., Steinthorsdottir, V., 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., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Hassanali, N., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lindgren, C.M., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., 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., Morris, A.D., Palmer, C.N., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Pedersen, O., 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., Soranzo, N., Wheeler, E., Glazer, N.L., Bouatia-Naji, N., Mägi, R., Randall, J., Elliott, P., Rybin, D., Dehghan, A., Hottenga, J.J., Song, K., Goel, A., Lajunen, T., Doney, A., Cavalcanti-Proença, C., Kumari, M., Timpson, N.J., Zabena, C., Ingelsson, E., An, P., O'Connell, J., Luan, J., Elliott, A., Roccasecca, R.M., Pattou, F., Sethupathy, P., Ariyurek, Y., Barter, P., Beilby, J.P., Ben-Shlomo, Y., Bergmann, S., Bochud, M., Bonnefond, A., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, S.J., Chen, Y.D., Chines, P., Clarke, R., Coin, L.J., Cooper, M.N., Crisponi, L., Day, I.N., de Geus, E.J., Delplanque, J., Fedson, A.C., Fischer-Rosinsky, A., Forouhi, N.G., Franzosi, M.G., Galan, P., Goodarzi, M.O., Graessler, J., Grundy, S., Gwilliam, R., Hallmans, G., Hammond, N., Han, X., Hartikainen, A.L., Hayward, C., Heath, S.C., Hercberg, S., Hillman, D.R., Hingorani, A.D., Hui, J., Hung, J., Kaakinen, M., Kaprio, J., Kesaniemi, Y.A., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, K.O., Lathrop, G.M., Lawlor, D.A., Le Bacquer, O., Lecoeur, C., Li, Y., Mahley, R., Mangino, M., Martínez-Larrad, M.T., McAteer, J.B., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, B.D., Mukherjee, S., Naitza, S., Neville, M.J., Orrù, M., Pakyz, R., Paolisso, G., Pattaro, C., Pearson, D., Peden, J.F., Pedersen, N.L., Pfeiffer, A.F., Pichler, I., Polasek, O., Posthuma, D., Potter, S.C., Pouta, A., Province, M.A., Rice, K., Ripatti, S., Rivadeneira, F., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, A.A., Scheet, P., Seedorf, U., Sharp, S.J., Shields, B., Sigurðsson, G., Sijbrands, E.J., Silveira, A., Simpson, L., Singleton, A., Smith, N.L., Sovio, U., Swift, A., Syddall, H., Syvänen, A.C., Tönjes, A., Uitterlinden, A.G., van Dijk, K.W., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, P.J., Walley, A., Ward, K.L., Watkins, H., Wild, S.H., Willemsen, G., Witteman, J.C., Yarnell, J.W., Zelenika, D., Zethelius, B., Zhai, G., Zhao, J.H., Zillikens, M.C., Borecki, I.B., Meneton, P., Magnusson, P.K., Nathan, D.M., Williams, G.H., Silander, K., Bornstein, S.R., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, A.R., Cooper, C., Serrano-Ríos, M., Lind, L., Palmer, L.J., Franks, P.W., Ebrahim, S., Marmot, M., Wright, A.F., Stumvoll, M., Hamsten, A., Buchanan, T.A., Valle, T.T., Rotter, J.I., Penninx, B.W., Boomsma, D.I., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, M.R., Peltonen, L., Mooser, V., Musunuru, K., Smith, A.V., Edmondson, A.C., Stylianou, I.M., Koseki, M., Pirruccello, J.P., Chasman, D.I., Johansen, C.T., Fouchier, S.W., Peloso, G.M., Barbalic, M., Ricketts, S.L., Bis, J.C., Feitosa, M.F., Orho-Melander, M., Melander, O., Li, X., Cho, Y.S., Go, M.J., Kim, Y.J., Lee, J.Y., Park, T., Kim, K., Sim, X., Ong, R.T., Croteau-Chonka, D.C., Lange, L.A., Smith, J.D., Ziegler, A., Zhang, W., Zee, R.Y., Whitfield, J.B., Thompson, J.R., Surakka, I., Smit, J.H., Sinisalo, J., Scott, J., Saharinen, J., Sabatti, C., Rose, L.M., Roberts, R., Rieder, M., Parker, A.N., Pare, G., O'Donnell, C.J., Nieminen, M.S., Nickerson, D.A., Montgomery, G.W., McArdle, W., Masson, D., Martin, N.G., Marroni, F., Lucas, G., Luben, R., Lokki, M.L., Lettre, G., Launer, L.J., Lakatta, E.G., Laaksonen, R., König, I.R., Khaw, K.T., Kaplan, L.M., Johansson, Å., Janssens, A.C., Igl, W., Hovingh, G.K., Hengstenberg, C., Havulinna, A.S., Hastie, N.D., Harris, T.B., Haritunians, T., Hall, A.S., Groop, L.C., Gonzalez, E., Freimer, N.B., Erdmann, J., Ejebe, K.G., Döring, A., Dominiczak, A.F., Demissie, S., de Faire, U., Caulfield, M.J., Boekholdt, S.M., Assimes, T.L., Quertermous, T., Seielstad, M., Wong, T.Y., Tai, E.S., Feranil, A.B., Kuzawa, C.W., Taylor, H.A., Gabriel, S.B., Holm, H., Gudnason, V., Krauss, R.M., Ordovas, J.M., Munroe, P.B., Kooner, J.S., Tall, A.R., Hegele, R.A., Kastelein, J.J., Schadt, E.E., Strachan, D.P., Reilly, M.P., Samani, N.J., Schunkert, H., Cupples, L.A., Sandhu, M.S., Ridker, P.M., Rader, D.J., and Kathiresan, S.
- Abstract
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
- Published
- 2012
10. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
- Author
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Heid, I.M., Jackson, A.U., Randall, J.C., Winkler, T.W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M.C., Speliotes, E.K., Mägi, R., Workalemahu, T., White, C.C., Bouatia-Naji, N., Harris, T.B., Berndt, S.I., Ingelsson, E., Willer, C.J., Weedon, M.N., Luan, J., Vedantam, S., Esko, T., Kilpeläinen, T.O., Kutalik, Z., Li, S., Monda, K.L., Dixon, A.L., Holmes, C.C., Kaplan, L.M., Liang, L., Min, J.L., Moffatt, M.F., Molony, C., Nicholson, G., Schadt, E.E., Zondervan, K.T., Feitosa, M.F., Ferreira, T., Allen, H.L., Weyant, R.J., Wheeler, E., Wood, A.R., MAGIC, Estrada, K., Goddard, M.E., Lettre, G., Mangino, M., Nyholt, D.R., Purcell, S., Smith, A.V., Visscher, P.M., Yang, J., McCarroll, S.A., Nemesh, J., Voight, B.F., Absher, D., Amin, N., Aspelund, T., Coin, L., Glazer, N.L., Hayward, C., Heard-Costa, N.L., Hottenga, J.J., Johansson, A., Johnson, T., Kaakinen, M., Kapur, K., Ketkar, S., Knowles, J.W., Kraft, P., Kraja, A.T., Lamina, C., Leitzmann, M.F., McKnight, B., Morris, A.P., Ong, K.K., Perry, J.R., Peters, M.J., Polasek, O., Prokopenko, I., Rayner, N.W., Ripatti, S., Rivadeneira, F., Robertson, N.R., Sanna, S., Sovio, U., Surakka, I., Teumer, A., van Wingerden, S., Vitart, V., Zhao, J.H., Cavalcanti-Proença, C., Chines, P.S., Fisher, E., Kulzer, J.R., Lecoeur, C., Narisu, N., Sandholt, C., Scott, L.J., Silander, K., Stark, K., Tammesoo, M.L., Teslovich, T.M., Timpson, N.J., Watanabe, R.M., Welch, R., Chasman, D.I., Cooper, M.N., Jansson, J.O., Kettunen, J., Lawrence, R.W., Pellikka, N., Perola, M., Vandenput, L., Alavere, H., Almgren, P., Atwood, L.D., Bennett, A.J., Biffar, R., Bonnycastle, L.L., Bornstein, S.R., Buchanan, T.A., Campbell, H., Day, I.N., Dei, M., Dörr, M., Elliott, P., Erdos, M.R., Eriksson, J.G., Freimer, N.B., Fu, M., Gaget, S., Geus, E.J., Gjesing, A.P., Grallert, H., Grässler, J., Groves, C.J., Guiducci, C., Hartikainen, A.L., Hassanali, N., Havulinna, A.S., Herzig, K.H., Hicks, A.A., Hui, J., Igl, W., Jousilahti, P., Jula, A., Kajantie, E., Kinnunen, L., Kolcic, I., Koskinen, S., Kovacs, P., Kroemer, H.K., Krzelj, V., Kuusisto, J., Kvaloy, K., Laitinen, J., Lantieri, O., Lathrop, G.M., Lokki, M.L., Luben, R.N., Ludwig, B., McArdle, W.L., McCarthy, A., Morken, M.A., Nelis, M., Neville, M.J., Paré, G., Parker, A.N., Peden, J.F., Pichler, I., Pietiläinen, K.H., Platou, C.G., Pouta, A., Ridderstråle, M., Samani, N.J., Saramies, J., Sinisalo, J., Smit, J.H., Strawbridge, R.J., Stringham, H.M., Swift, A.J., Teder-Laving, M., Thomson, B., Usala, G., van Meurs, J.B., van Ommen, G.J., Vatin, V., Volpato, C.B., Wallaschofski, H., Walters, G.B., Widen, E., Wild, S.H., Willemsen, G., Witte, D.R., Zgaga, L., Zitting, P., Beilby, J.P., James, A.L., Kähönen, M., Lehtimäki, T., Nieminen, M.S., Ohlsson, C., Palmer, L.J., Raitakari, O., Ridker, P.M., Stumvoll, M., Tönjes, A., Viikari, J., Balkau, B., Ben-Shlomo, Y., Bergman, R.N., Boeing, H., Smith, G.D., Ebrahim, S., Froguel, P., Hansen, T., Hengstenberg, C., Hveem, K., Isomaa, B., Jørgensen, T., Karpe, F., Khaw, K.T., Laakso, M., Lawlor, D.A., Marre, M., Meitinger, T., Metspalu, A., Midthjell, K., Pedersen, O., Salomaa, V., Schwarz, P.E., Tuomi, T., Tuomilehto, J., Valle, T.T., Wareham, N.J., Arnold, A.M., Beckmann, J.S., Bergmann, S., Boerwinkle, E., Boomsma, D.I., Caulfield, M.J., Collins, F.S., Eiriksdottir, G., Gudnason, V., Gyllensten, U., Hamsten, A., Hattersley, A.T., Hofman, A., Hu, F.B., Illig, T., Iribarren, C., Jarvelin, M.R., Kao, W.H., Kaprio, J., Launer, L.J., Munroe, P.B., Oostra, B., Penninx, B.W., Pramstaller, P.P., Psaty, B.M., Quertermous, T., Rissanen, A., Rudan, I., Shuldiner, A.R., Soranzo, N., Spector, T.D., Syvanen, A.C., Uda, M., Uitterlinden, A., Völzke, H., Vollenweider, P., Wilson, J.F., Witteman, J.C., Wright, A.F., Abecasis, G.R., Boehnke, M., Borecki, I.B., Deloukas, P., Frayling, T.M., Groop, L.C., Haritunians, T., Hunter, D.J., Kaplan, R.C., North, K.E., O'Connell, J.R., Peltonen, L., Schlessinger, D., Strachan, D.P., Hirschhorn, J.N., Assimes, T.L., Wichmann, H.E., Thorsteinsdottir, U., van Duijn, C.M., Stefansson, K., Cupples, L.A., Loos, R.J., Barroso, I., McCarthy, M.I., Fox, C.S., Mohlke, K.L., Lindgren, C.M., Heid, I.M., Jackson, A.U., Randall, J.C., Winkler, T.W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M.C., Speliotes, E.K., Mägi, R., Workalemahu, T., White, C.C., Bouatia-Naji, N., Harris, T.B., Berndt, S.I., Ingelsson, E., Willer, C.J., Weedon, M.N., Luan, J., Vedantam, S., Esko, T., Kilpeläinen, T.O., Kutalik, Z., Li, S., Monda, K.L., Dixon, A.L., Holmes, C.C., Kaplan, L.M., Liang, L., Min, J.L., Moffatt, M.F., Molony, C., Nicholson, G., Schadt, E.E., Zondervan, K.T., Feitosa, M.F., Ferreira, T., Allen, H.L., Weyant, R.J., Wheeler, E., Wood, A.R., MAGIC, Estrada, K., Goddard, M.E., Lettre, G., Mangino, M., Nyholt, D.R., Purcell, S., Smith, A.V., Visscher, P.M., Yang, J., McCarroll, S.A., Nemesh, J., Voight, B.F., Absher, D., Amin, N., Aspelund, T., Coin, L., Glazer, N.L., Hayward, C., Heard-Costa, N.L., Hottenga, J.J., Johansson, A., Johnson, T., Kaakinen, M., Kapur, K., Ketkar, S., Knowles, J.W., Kraft, P., Kraja, A.T., Lamina, C., Leitzmann, M.F., McKnight, B., Morris, A.P., Ong, K.K., Perry, J.R., Peters, M.J., Polasek, O., Prokopenko, I., Rayner, N.W., Ripatti, S., Rivadeneira, F., Robertson, N.R., Sanna, S., Sovio, U., Surakka, I., Teumer, A., van Wingerden, S., Vitart, V., Zhao, J.H., Cavalcanti-Proença, C., Chines, P.S., Fisher, E., Kulzer, J.R., Lecoeur, C., Narisu, N., Sandholt, C., Scott, L.J., Silander, K., Stark, K., Tammesoo, M.L., Teslovich, T.M., Timpson, N.J., Watanabe, R.M., Welch, R., Chasman, D.I., Cooper, M.N., Jansson, J.O., Kettunen, J., Lawrence, R.W., Pellikka, N., Perola, M., Vandenput, L., Alavere, H., Almgren, P., Atwood, L.D., Bennett, A.J., Biffar, R., Bonnycastle, L.L., Bornstein, S.R., Buchanan, T.A., Campbell, H., Day, I.N., Dei, M., Dörr, M., Elliott, P., Erdos, M.R., Eriksson, J.G., Freimer, N.B., Fu, M., Gaget, S., Geus, E.J., Gjesing, A.P., Grallert, H., Grässler, J., Groves, C.J., Guiducci, C., Hartikainen, A.L., Hassanali, N., Havulinna, A.S., Herzig, K.H., Hicks, A.A., Hui, J., Igl, W., Jousilahti, P., Jula, A., Kajantie, E., Kinnunen, L., Kolcic, I., Koskinen, S., Kovacs, P., Kroemer, H.K., Krzelj, V., Kuusisto, J., Kvaloy, K., Laitinen, J., Lantieri, O., Lathrop, G.M., Lokki, M.L., Luben, R.N., Ludwig, B., McArdle, W.L., McCarthy, A., Morken, M.A., Nelis, M., Neville, M.J., Paré, G., Parker, A.N., Peden, J.F., Pichler, I., Pietiläinen, K.H., Platou, C.G., Pouta, A., Ridderstråle, M., Samani, N.J., Saramies, J., Sinisalo, J., Smit, J.H., Strawbridge, R.J., Stringham, H.M., Swift, A.J., Teder-Laving, M., Thomson, B., Usala, G., van Meurs, J.B., van Ommen, G.J., Vatin, V., Volpato, C.B., Wallaschofski, H., Walters, G.B., Widen, E., Wild, S.H., Willemsen, G., Witte, D.R., Zgaga, L., Zitting, P., Beilby, J.P., James, A.L., Kähönen, M., Lehtimäki, T., Nieminen, M.S., Ohlsson, C., Palmer, L.J., Raitakari, O., Ridker, P.M., Stumvoll, M., Tönjes, A., Viikari, J., Balkau, B., Ben-Shlomo, Y., Bergman, R.N., Boeing, H., Smith, G.D., Ebrahim, S., Froguel, P., Hansen, T., Hengstenberg, C., Hveem, K., Isomaa, B., Jørgensen, T., Karpe, F., Khaw, K.T., Laakso, M., Lawlor, D.A., Marre, M., Meitinger, T., Metspalu, A., Midthjell, K., Pedersen, O., Salomaa, V., Schwarz, P.E., Tuomi, T., Tuomilehto, J., Valle, T.T., Wareham, N.J., Arnold, A.M., Beckmann, J.S., Bergmann, S., Boerwinkle, E., Boomsma, D.I., Caulfield, M.J., Collins, F.S., Eiriksdottir, G., Gudnason, V., Gyllensten, U., Hamsten, A., Hattersley, A.T., Hofman, A., Hu, F.B., Illig, T., Iribarren, C., Jarvelin, M.R., Kao, W.H., Kaprio, J., Launer, L.J., Munroe, P.B., Oostra, B., Penninx, B.W., Pramstaller, P.P., Psaty, B.M., Quertermous, T., Rissanen, A., Rudan, I., Shuldiner, A.R., Soranzo, N., Spector, T.D., Syvanen, A.C., Uda, M., Uitterlinden, A., Völzke, H., Vollenweider, P., Wilson, J.F., Witteman, J.C., Wright, A.F., Abecasis, G.R., Boehnke, M., Borecki, I.B., Deloukas, P., Frayling, T.M., Groop, L.C., Haritunians, T., Hunter, D.J., Kaplan, R.C., North, K.E., O'Connell, J.R., Peltonen, L., Schlessinger, D., Strachan, D.P., Hirschhorn, J.N., Assimes, T.L., Wichmann, H.E., Thorsteinsdottir, U., van Duijn, C.M., Stefansson, K., Cupples, L.A., Loos, R.J., Barroso, I., McCarthy, M.I., Fox, C.S., Mohlke, K.L., and Lindgren, C.M.
- Abstract
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
- Published
- 2010
11. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.
- Author
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Willer, C.J., Speliotes, E.K., Loos, R.J., Li, S., Lindgren, C.M., Heid, I.M., Berndt, S.I., Elliott, A.L., Jackson, A.U., Lamina, C., Lettre, G., Lim, N., Lyon, H.N., McCarroll, S.A., Papadakis, K., Qi, L., Randall, J.C., Roccasecca, R.M., Sanna, S., Scheet, P., Weedon, M.N., Wheeler, E., Zhao, J.H., Jacobs, L.C., Prokopenko, I., Soranzo, N., Tanaka, T., Timpson, N.J., Almgren, P., Bennett, A., Bergman, R.N., Bingham, S.A., Bonnycastle, L.L., Brown, M., Burtt, N.P., Chines, P., Coin, L., Collins, F.S., Connell, J.M., Cooper, C., Smith, G.D., Dennison, E.M., Deodhar, P., Elliott, P., Erdos, M.R., Estrada, K., Evans, D.M., Gianniny, L., Gieger, C., Gillson, C.J., Guiducci, C., Hackett, R., Hadley, D., Hall, A.S., Havulinna, A.S., Hebebrand, J., Hofman, A., Isomaa, B., Jacobs, K.B., Johnson, T., Jousilahti, P., Jovanovic, Z., Khaw, K.T., Kraft, P., Kuokkanen, M., Kuusisto, J., Laitinen, J., Lakatta, E.G., Luan, J., Luben, R.N., Mangino, M., McArdle, W.L., Meitinger, T., Mulas, A., Munroe, P.B., Narisu, N., Ness, A.R., Northstone, K., O'Rahilly, S., Purmann, C., Rees, M.G., Ridderstråle, M., Ring, S.M., Rivadeneira, F., Ruokonen, A., Sandhu, M.S., Saramies, J., Scott, L.J., Scuteri, A., Silander, K., Sims, M.A., Song, K., Stephens, J., Stevens, S., Stringham, H.M., Tung, Y.C., Valle, T.T., Van Duijn, C.M., Vimaleswaran, K.S., Vollenweider, P., Waeber, G., Wallace, C., Watanabe, R.M., Waterworth, D.M., Watkins, N., Witteman, J.C., Zeggini, E., Zhai, G., Zillikens, M.C., Altshuler, D., Caulfield, M.J., Chanock, S.J., Farooqi, I.S., Ferrucci, L., Guralnik, J.M., Hattersley, A.T., Hu, F.B., Jarvelin, M.R., Laakso, M., Mooser, V., Ong, K.K., Ouwehand, W.H., Salomaa, V., Samani, N.J., Spector, T.D., Tuomi, T., Tuomilehto, J., Uda, M., Uitterlinden, A.G., Wareham, N.J., Deloukas, P., Frayling, T.M., Groop, L.C., Hayes, R.B., Hunter, D.J., Mohlke, K.L., Peltonen, L., Schlessinger, D., Strachan, D.P., Wichmann, H.E., McCarthy, M.I., Boehnke, M., Barroso, I., Abecasis, G.R., Hirschhorn, J.N., Willer, C.J., Speliotes, E.K., Loos, R.J., Li, S., Lindgren, C.M., Heid, I.M., Berndt, S.I., Elliott, A.L., Jackson, A.U., Lamina, C., Lettre, G., Lim, N., Lyon, H.N., McCarroll, S.A., Papadakis, K., Qi, L., Randall, J.C., Roccasecca, R.M., Sanna, S., Scheet, P., Weedon, M.N., Wheeler, E., Zhao, J.H., Jacobs, L.C., Prokopenko, I., Soranzo, N., Tanaka, T., Timpson, N.J., Almgren, P., Bennett, A., Bergman, R.N., Bingham, S.A., Bonnycastle, L.L., Brown, M., Burtt, N.P., Chines, P., Coin, L., Collins, F.S., Connell, J.M., Cooper, C., Smith, G.D., Dennison, E.M., Deodhar, P., Elliott, P., Erdos, M.R., Estrada, K., Evans, D.M., Gianniny, L., Gieger, C., Gillson, C.J., Guiducci, C., Hackett, R., Hadley, D., Hall, A.S., Havulinna, A.S., Hebebrand, J., Hofman, A., Isomaa, B., Jacobs, K.B., Johnson, T., Jousilahti, P., Jovanovic, Z., Khaw, K.T., Kraft, P., Kuokkanen, M., Kuusisto, J., Laitinen, J., Lakatta, E.G., Luan, J., Luben, R.N., Mangino, M., McArdle, W.L., Meitinger, T., Mulas, A., Munroe, P.B., Narisu, N., Ness, A.R., Northstone, K., O'Rahilly, S., Purmann, C., Rees, M.G., Ridderstråle, M., Ring, S.M., Rivadeneira, F., Ruokonen, A., Sandhu, M.S., Saramies, J., Scott, L.J., Scuteri, A., Silander, K., Sims, M.A., Song, K., Stephens, J., Stevens, S., Stringham, H.M., Tung, Y.C., Valle, T.T., Van Duijn, C.M., Vimaleswaran, K.S., Vollenweider, P., Waeber, G., Wallace, C., Watanabe, R.M., Waterworth, D.M., Watkins, N., Witteman, J.C., Zeggini, E., Zhai, G., Zillikens, M.C., Altshuler, D., Caulfield, M.J., Chanock, S.J., Farooqi, I.S., Ferrucci, L., Guralnik, J.M., Hattersley, A.T., Hu, F.B., Jarvelin, M.R., Laakso, M., Mooser, V., Ong, K.K., Ouwehand, W.H., Salomaa, V., Samani, N.J., Spector, T.D., Tuomi, T., Tuomilehto, J., Uda, M., Uitterlinden, A.G., Wareham, N.J., Deloukas, P., Frayling, T.M., Groop, L.C., Hayes, R.B., Hunter, D.J., Mohlke, K.L., Peltonen, L., Schlessinger, D., Strachan, D.P., Wichmann, H.E., McCarthy, M.I., Boehnke, M., Barroso, I., Abecasis, G.R., and Hirschhorn, J.N.
- Abstract
Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
- Published
- 2009
12. Variants in MTNR1B influence fasting glucose levels
- Author
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Prokopenko, I., Langenberg, C., Florez, J.C., Saxena, R., Soranzo, N., Thorleifsson, G., Loos, R.J.F., Manning, A.K., Jackson, A.U., Aulchenko, Y.S., Potter, S.C., Erdos, M.R., Sanna, S., Hottenga, J.J., Wheeler, E., Kaakinen, M., Lyssenko, V., Chen, W.-M., Ahmadi, K., Beckmann, J.S., Bergman, R.N., Bochud, M., Bonnycastle, L.L., Buchanan, T.A., Cao, A., Cervin, A., Coin, L., Collins, F.S., Crisponi, L., de Geus, E.J.C., Dehghan, A., Deloukas, P., Doney, A.S.F., Elliott, P., Freimer, N.B., Gateva, V., Herder, C., Hofman, A., Hughes, T.E., Hunt, S., Illig, T., Inouye, M., Isomaa, B., Johnson, T., Kong, A., Krestyaninova, M., Kuusisto, J., Laaks, M., Lim, N., Lindblad, U., Lindgren, C.M., McCann, O.T., Mohlke, K.L., Morris, A.D., Naitza, S., Orrù, M., Palmer, C.N.A., Pouta, A., Randall, J., Rathmann, W., Saramies, J., Scheet, P., Scott, L.J., Scuteri, A., Sharp, S., Sijbrands, E.J.G., Smit, J.H., Song, K., Steinthorsdottir, V., Stringham, H.M., Tuomi, T., Tuomilehto, J., Uitterlinden, A.G., Voight, B.F., Waterworth, D., Wichmann, H.-E., Willemsen, G., Witteman, J.C.M., Yuan, X., Zha, J.H., Zeggini, E., Schlessinger, D., Sandhu, M., Boomsma, D.I., Uda, M., Spector, T.D., Penninx, B.W.J.H., Altshuler, D., Vollenweider, P., Jarvelin, M.-R., Lakatta, E., Waeber, G., Fox, C.S., Peltonen, L., Groop, L.C., Mooser, V., Cupples, L.A., Thorsteinsdottir, U., Abecasis, G.R., Prokopenko, I., Langenberg, C., Florez, J.C., Saxena, R., Soranzo, N., Thorleifsson, G., Loos, R.J.F., Manning, A.K., Jackson, A.U., Aulchenko, Y.S., Potter, S.C., Erdos, M.R., Sanna, S., Hottenga, J.J., Wheeler, E., Kaakinen, M., Lyssenko, V., Chen, W.-M., Ahmadi, K., Beckmann, J.S., Bergman, R.N., Bochud, M., Bonnycastle, L.L., Buchanan, T.A., Cao, A., Cervin, A., Coin, L., Collins, F.S., Crisponi, L., de Geus, E.J.C., Dehghan, A., Deloukas, P., Doney, A.S.F., Elliott, P., Freimer, N.B., Gateva, V., Herder, C., Hofman, A., Hughes, T.E., Hunt, S., Illig, T., Inouye, M., Isomaa, B., Johnson, T., Kong, A., Krestyaninova, M., Kuusisto, J., Laaks, M., Lim, N., Lindblad, U., Lindgren, C.M., McCann, O.T., Mohlke, K.L., Morris, A.D., Naitza, S., Orrù, M., Palmer, C.N.A., Pouta, A., Randall, J., Rathmann, W., Saramies, J., Scheet, P., Scott, L.J., Scuteri, A., Sharp, S., Sijbrands, E.J.G., Smit, J.H., Song, K., Steinthorsdottir, V., Stringham, H.M., Tuomi, T., Tuomilehto, J., Uitterlinden, A.G., Voight, B.F., Waterworth, D., Wichmann, H.-E., Willemsen, G., Witteman, J.C.M., Yuan, X., Zha, J.H., Zeggini, E., Schlessinger, D., Sandhu, M., Boomsma, D.I., Uda, M., Spector, T.D., Penninx, B.W.J.H., Altshuler, D., Vollenweider, P., Jarvelin, M.-R., Lakatta, E., Waeber, G., Fox, C.S., Peltonen, L., Groop, L.C., Mooser, V., Cupples, L.A., Thorsteinsdottir, U., and Abecasis, G.R.
- Abstract
To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 × 10
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- 2009
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13. Molecular correlates for maximal oxygen uptake and type 1 fibers
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Parikh, H., Nilsson, E., Ling, C., Poulsen, P., Almgren, P., Nittby, H., Eriksson, K.F., Vaag, A., Groop, L.C., Parikh, H., Nilsson, E., Ling, C., Poulsen, P., Almgren, P., Nittby, H., Eriksson, K.F., Vaag, A., and Groop, L.C.
- Abstract
Udgivelsesdato: 2008
- Published
- 2008
14. The Acute Effect of Preprandial Exogenous and Endogenous Sulphonylurea‐stimulated Insulin Secretion on Postprandial Glucose Excursions in Patients with Type 2 Diabetes
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Groop, P.‐H., primary, Melander, A., additional, and Groop, L.C., additional
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- 1993
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15. ACE inhibitor slows diabetes-related renal disease
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Viberti, G., Morgensen, C.E., and Groop. L.C.
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ACE inhibitors -- Health aspects ,Captopril -- Health aspects ,Kidney diseases -- Care and treatment ,Type 2 diabetes -- Care and treatment ,Health ,Seniors - Abstract
A randomized, double-blind, placebo-controlled study revealed that the ACE inhibitor captopril can be used to retard the development of renal disorders in normotensive patients suffering from non-insulin-dependent diabetes mellitus. The study indicated that captopril slows the progression of clinical proteinuria and that the therapy will not affect glomerular filtration rates and glycosylated hemoglobin values., The ACE inhibitor captopril slows the progression of renal disease in normotensive patients with insulin-dependent diabetes mellitus (IDDM) and persistent microalbuminuria, report the authors of this randomized, double-blind, placebo-controlled study. [...]
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- 1994
16. Polymorphisms of the HDL Receptor Gene Associated with HDL Cholesterol Levels in Diabetic Kindred from Three Populations
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McCarthy, J.J., Lewitzky, S., Reeves, C., Permutt, A., Glaser, B., Groop, L.C., Lehner, T., and Meyer, J.M.
- Abstract
Abstract Objective: We examined polymorphisms in the HDL receptor, SR-BI, for association with plasma HDL cholesterol levels. Methods: Study subjects, including 847 women and 725 men, were from families originally ascertained for type 2 diabetes from Finland, Sweden and Israel. Four common polymorphisms were examined in linear regression analysis: an exon 1 missense (EX1), exon 8 silent (EX8), intron 5 (IVS5) and intron 10 (IVS10) variants. Results: Genotype combinations for the three polymorphisms in linkage disequilibrium (IVS5, EX8 and IVS10) were found to be associated with HDL-C among women from the Israeli (p = 0.01) and Swedish (p = 0.06) populations. In Finnish women, the association was only apparent after taking into account effect modification by triglyceride levels (p = 0.04). One specific pattern of genotypes, denoted by presence of the IVS5_T and EX8_C alleles, and absence of the IVS10_G allele, was consistently associated with the lowest mean levels of HDL-C in women from all three populations. These same associations were not found in men. Conclusions: Polymorphic variation of the SR-BI gene may influence HDL-C levels and act in a sex-dependent manner.Copyright © 2003 S. Karger AG, Basel- Published
- 2003
17. Pathogenesis of Insulin Resistance in Type 2 Diabetes: A Collision between Thrifty Genes and an Affluent Environment.
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Groop, L.C.
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- *
INSULIN resistance , *TYPE 2 diabetes , *DIABETES - Abstract
Presents information on the pathogenesis of insulin resistance in type 2 diabetes. Approaches being used in the search for the thrifty genes predisposing to type 2 diabetes; Information on the metabolic or the insulin resistance syndrome; Influence of thrifty genes and affluent environment on the development of type 2 diabetes.
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- 1999
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18. Hyperglycemia and absorption of sulphonylurea drugs.
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Groop, L.C. and Luzi, L.
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BLOOD diseases - Abstract
Presents research measuring plasma concentrations of glipizide during four levels of glycemia in healthy young subjects. Methods.
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- 1989
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19. Defining the role of common variation in the genomic and biological architecture of adult human height
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Wood, Ar, Esko, T, Yang, J, Vedantam, S, Pers, Th, Gustafsson, S, Chu, Ay, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, Ml, Croteau Chonka DC, Day, Fr, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, Au, Karjalainen, J, Lo, Ks, Locke, Ae, Mägi, R, Mihailov, E, Porcu, E, Randall, Jc, Scherag, A, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Workalemahu, T, Zhao, Jh, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, Gb, Feenstra, B, Feitosa, Mf, Fischer, K, Fraser, Rm, Goel, A, Gong, J, Justice, Ae, Kanoni, S, Kleber, Me, Kristiansson, K, Lim, U, Lotay, V, Lui, Jc, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, Js, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, Rj, Sung, Yj, Tanaka, T, Teumer, A, Trompet, S, van der Laan SW, van Setten, J, Van Vliet Ostaptchouk JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlöv, J, Arscott, Gm, Bandinelli, S, Barrett, A, Bellis, C, Bennett, Aj, Berne, C, Blüher, M, Bolton, Jl, Böttcher, Y, Boyd, Ha, Bruinenberg, M, Buckley, Bm, Buyske, S, Caspersen, Ih, Chines, Ps, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, Ew, De Jong PA, Deelen, J, Delgado, G, Denny, Jc, Dhonukshe Rutten, R, Dimitriou, M, Doney, As, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, Me, Geller, F, Giedraitis, V, Go, As, Grallert, H, Grammer, Tb, Gräßler, J, Grönberg, H, de Groot LC, Groves, Cj, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, Ca, Hassinen, M, Hayward, C, Heard Costa NL, Helmer, Q, Hemani, G, Henders, Ak, Hillege, Hl, Hlatky, Ma, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat JJ, Illig, T, Isaacs, A, James, Al, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, An, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, Pk, Mahajan, A, Maillard, M, Mcardle, Wl, Mckenzie, Ca, Mclachlan, S, Mclaren, Pj, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, Kl, Morken, Ma, Müller, G, Müller Nurasyid, M, Musk, Aw, Narisu, N, Nauck, M, Nolte, Im, Nöthen, Mm, Oozageer, L, Pilz, S, Rayner, Nw, Renstrom, F, Robertson, Nr, Rose, Lm, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, Fr, Schunkert, H, Scott, Ra, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, Jh, Smith, Av, Smolonska, J, Stanton, Av, Stirrups, K, Stott, Dj, Stringham, Hm, Sundström, J, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Thorleifsson, G, Tyrer, Jp, van Dijk, S, van Schoor NM, van der Velde, N, van Heemst, D, van Oort FV, Vermeulen, Sh, Verweij, N, Vonk, Jm, Waite, Ll, Waldenberger, M, Wennauer, R, Wilkens, Lr, Willenborg, C, Wilsgaard, T, Wojczynski, Mk, Wong, A, Wright, Af, Zhang, Q, Arveiler, D, Bakker, Sj, Beilby, J, Bergman, Rn, Bergmann, S, Biffar, R, Blangero, J, Boomsma, Di, Bornstein, Sr, Bovet, P, Brambilla, P, Brown, Mj, Campbell, H, Caulfield, Mj, Chakravarti, A, Collins, R, Collins, Fs, Crawford, Dc, Cupples, La, Danesh, J, de Faire, U, den Ruijter HM, Erbel, R, Erdmann, J, Eriksson, Jg, Farrall, M, Ferrannini, Eleuterio, Ferrières, J, Ford, I, Forouhi, Ng, Forrester, T, Gansevoort, Rt, Gejman, Pv, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, Dw, Hall, As, Harris, Tb, Hattersley, At, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hofman, A, Hovingh, Gk, Humphries, Se, Hunt, Sc, Hypponen, E, Jacobs, Kb, Jarvelin, Mr, Jousilahti, P, Jula, Am, Kaprio, J, Kastelein, Jj, Kayser, M, Kee, F, Keinanen Kiukaanniemi SM, Kiemeney, La, Kooner, Js, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, At, Kumari, M, Kuusisto, J, Lakka, Ta, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, Pa, Männistö, S, Manunta, P, Marette, A, Matise, Tc, Mcknight, B, Meitinger, T, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Nelis, M, Ohlsson, C, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pasterkamp, G, Peters, A, Pramstaller, Pp, Price, Jf, Qi, L, Raitakari, Ot, Rankinen, T, Rao, Dc, Rice, Tk, Ritchie, M, Rudan, I, Salomaa, V, Samani, Nj, Saramies, J, Sarzynski, Ma, Schwarz, Pe, Sebert, S, Sever, P, Shuldiner, Ar, Sinisalo, J, Steinthorsdottir, V, Stolk, Rp, Tardif, Jc, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, Mc, Electronic Medical Records, Genomics, Consortium, Migen, Consortium, Pagege, Consortium, LifeLines Cohort Study, Amouyel, P, Asselbergs, Fw, Assimes, Tl, Bochud, M, Boehm, Bo, Boerwinkle, E, Bottinger, Ep, Bouchard, C, Cauchi, S, Chambers, Jc, Chanock, Sj, Cooper, Rs, de Bakker PI, Dedoussis, G, Ferrucci, L, Franks, Pw, Froguel, P, Groop, Lc, Haiman, Ca, Hamsten, A, Hayes, Mg, Hui, J, Hunter, Dj, Hveem, K, Jukema, Jw, Kaplan, Rc, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, Ng, März, W, Melbye, M, Moebus, S, Munroe, Pb, Njølstad, I, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Perola, M, Pérusse, L, Peters, U, Powell, Je, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, Pm, Rivadeneira, F, Rotter, Ji, Saaristo, Te, Saleheen, D, Schlessinger, D, Slagboom, Pe, Snieder, H, Spector, Td, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, Nj, Watkins, H, Wichmann, He, Wilson, Jf, Zanen, P, Deloukas, P, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, Thorsteinsdottir, U, Barroso, I, Fox, Cs, North, Ke, Strachan, Dp, Beckmann, Js, Berndt, Si, Boehnke, M, Borecki, Ib, Mccarthy, Mi, Metspalu, A, Stefansson, K, Uitterlinden, Ag, van Duijn CM, Franke, L, Willer, Cj, Price, Al, Lettre, G, Loos, Rj, Weedon, Mn, Ingelsson, E, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, T. M., Isotope Research, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Ehret, Georg Benedikt, Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Lui, J, Mangino, M, Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, Van Der Laan, S, Van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, P, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, De Groot, L, Groves, C, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, Van Dijk, S, Van Schoor, N, Van Der Velde, N, Van Heemst, D, Van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, D, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, De Faire, U, Den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, De Bakker, P, Dedoussis, G, 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Visscher, P, Hirschhorn, J, Frayling, T, Medical Research Council (MRC), APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., 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Hirschhorn, Jn, Frayling, Tm, Epidemiology, Surgery, Public Health, Internal Medicine, Erasmus MC other, Genetic Identification, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Biological Psychology, AIMMS, Functional Genomics, EMGO+ - Lifestyle, Overweight and Diabetes, Wood, AR, Vadantam, S, Hypponen, Elina, Frayling, TM, Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Amin N., Buchkovich M.L., Croteau-Chonka D.C., Day F.R., Duan Y., Fall T., Fehrmann R., Ferreira T., Jackson A.U., Karjalainen J., Lo K.S., Locke A.E., Magi R., Mihailov E., Porcu E., Randall J.C., Scherag A., Vinkhuyzen A.A.E., Westra H.-J., Winkler T.W., Workalemahu T., Zhao J.H., Absher D., Albrecht E., Anderson D., Baron J., Beekman M., Demirkan A., Ehret G.B., Feenstra B., Feitosa M.F., Fischer K., Fraser R.M., Goel A., Gong J., Justice A.E., Kanoni S., Kleber M.E., Kristiansson K., Lim U., Lotay V., Lui J.C., Mangino M., Leach I.M., 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Price A.L., Lettre G., Loos R.J.F., Weedon M.N., Ingelsson E., O'Connell J.R., Abecasis G.R., Chasman D.I., Goddard M.E., Visscher P.M., Hirschhorn J.N., and Frayling T.M.
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Netherlands Twin Register (NTR) ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Electronic Medical Records and Genomics (eMEMERGEGE) Consortium ,Medizin ,Genome-wide association study ,Adult ,Analysis of Variance ,Body Height/genetics ,European Continental Ancestry Group/genetics ,Genetic Variation/genetics ,Genetics, Population ,Genome-Wide Association Study/methods ,Humans ,Oligonucleotide Array Sequence Analysis ,Polymorphism, Single Nucleotide/genetics ,heritability ,0302 clinical medicine ,Genome-wide ,SNPS ,snps ,Genetics & Heredity ,ddc:616 ,Genetics ,Medical And Health Sciences ,0303 health sciences ,education.field_of_study ,variants ,GENETIC-VARIATION ,Biological Sciences ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,body height ,genetic-variation ,Life Sciences & Biomedicine ,Single Nucleotide/genetics ,Human ,European Continental Ancestry Group ,Population ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,NO ,complex traits ,03 medical and health sciences ,Genetic variation ,heritability, adult, height ,Polymorphism ,Human height ,PAGEGE Consortium ,education ,Gene ,VLAG ,030304 developmental biology ,Global Nutrition ,Wereldvoeding ,genome-wide association study ,Science & Technology ,Whites ,Oligonucleotide Array Sequence Analysi ,MUTATIONS ,COMPLEX TRAITS ,ta1184 ,Klinisk medicin ,population genetics ,Genetic Variation ,Heritability ,ta3121 ,mutations ,Genetic architecture ,Body Height ,genetic variation ,MIGen Consortium ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Clinical Medicine ,030217 neurology & neurosurgery ,height ,LifeLines Cohort Study ,Developmental Biology ,Genome-Wide Association Study - Abstract
Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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- 2014
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20. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease
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J., Buchkovich, M.L., Mora, S., Beckmann, J.S., Bragg-Gresham, J.L., Chang, H.Y., Demirkan, A., Den Hertog, H.M., Do, R., Donnelly, L.A., Ehret, G.B., Esko, T., Feitosa, M.F., Ferreira, T., Fischer, K., Fontanillas, P., Fraser, R.M., Freitag, D.F., Gurdasani, D., Heikkilä, K., Hyppönen, E., Isaacs, A., Jackson, A.U., Johansson, Å., Johnson, T., Kaakinen, M., Kettunen, J., Kleber, M.E., Li, X., Luan, J., Lyytikäinen, L.P., Magnusson, P.K., Mangino, M., Mihailov, E., Montasser, M.E., Nolte, I.M., O'Connell, J.R., Palmer, C.D., Petersen, A.K., Sanna, S., Saxena, R., Service, S.K., Shah, S., Shungin, D., Sidore, C., Song, C., Strawbridge, R.J., Surakka, I., Tanaka, T., Teslovich, T.M., Thorleifsson, G., Van den Herik, E.G., Voight, B.F., Volcik, K.A., Waite, L.L., Wong, A., Wu, Y., Zhang, W., Absher, D., Asiki, G., Barroso, I., Been, L.F., Bolton, J.L., Bonnycastle, L.L., Brambilla, P., Burnett, M.S., Cesana, G., Dimitriou, M., Doney, A.S., Döring, A., Elliott, P., Epstein, S.E., Eyjolfsson, G.I., Gigante, B., Goodarzi, M.O., Grallert, H., Gravito, M.L., Groves, C.J., Hallmans, G., Hartikainen, A.L., Hayward, C., Hernandez, D., Hicks, A.A., Holm, H., Hung, Y.J., Illig, T., Jones, M.R., Kaleebu, P., Kastelein, J.J., Khaw, K.T., Kim, E., Klopp, N., Komulainen, P., Kumari, M., Langenberg, C., Lehtimäki, T., Lin, S.Y., Lindström, J., Loos, R.J., Mach, F., McArdle, W.L., Meisinger, C., Mitchell, B.D., Müller, G., Nagaraja, R., Narisu, N., Nieminen, T.V., Nsubuga, R.N., Olafsson, I., Ong, K.K., Palotie, A., Papamarkou, T., Pomilla, C., Pouta, A., Reilly, M.P., Ridker, P.M., Rivadeneira, F., Rudan, I., Ruokonen, A., Scharnagl, H., Seeley, J., Silander, K., Stancáková, A., Stirrups, K., Swift, A.J., Tiret, L., Uitterlinden, A.G., van Pelt, L.J., Vedantam, S., Wainwright, N., Wijmenga, C., Wild, S.H., Willemsen, G., Wilsgaard, T., Wilson, J.F., Young, E.H., Zhao, J.H., Adair, L.S., Arveiler, D., Assimes, T.L., Bandinelli, S., Bennett, F., Bochud, M., Boehm, B.O., Boomsma, D.I., Borecki, I.B., Bornstein, S.R., Bovet, P., Burnier, M., Campbell, H., Chakravarti, A., Chambers, J.C., Chen, Y.D., Collins, F.S., Cooper, R.S., Dedoussis, G., de Faire, U., Feranil, A.B., Ferrucci, L., Freimer, N.B., Gieger, C., Groop, L.C., Gudnason, V., Gyllensten, U., Hamsten, A., Harris, T.B., Hingorani, A., Hirschhorn, J.N., Hofman, A., Hovingh, G.K., Hsiung, C.A., Humphries, S.E., Hunt, S.C., Hveem, K., Iribarren, C., Järvelin, M.R., Jula, A., Kähönen, M., Kaprio, J., Kesäniemi, A., Kivimaki, M., Kooner, J.S., Koudstaal, P.J., Krauss, R.M., Kuh, D., Kuusisto, J., Kyvik, K.O., Laakso, M., Lakka, T.A., Lind, L., Lindgren, C.M., Martin, N.G., März, W., McCarthy, M.I., McKenzie, C.A., Meneton, P., Metspalu, A., Moilanen, L., Morris, A.D., Munroe, P.B., Njølstad, I., Pedersen, N.L., Power, C., Pramstaller, P.P., Price, J.F., Psaty, B.M., Quertermous, T., Rauramaa, R., Salomaa, V., Sanghera, D.K., Saramies, J., Schwarz, P.E., Sheu, W.H., Shuldiner, A.R., Siegbahn, A., Spector, T.D., Stefansson, K., Strachan, D.P., Tayo, B.O., Tremoli, E., Tuomilehto, J., Uusitupa, M., van Duijn, C.M., Vollenweider, P., Wallentin, L., Wareham, N.J., Whitfield, J.B., Wolffenbuttel, B.H., Ordovas, J.M., Boerwinkle, E., Palmer, C.N., Thorsteinsdottir, U., Chasman, D.I., Rotter, J.I., Franks, P.W., Riatti, S., Cupples, L.A., Sandhu, M.S., Rich, S.S., Boehnke, M., Deloukas, P., Mohlke, K.L., Ingelsson, E., Gu, D., Roberts, R., Watkins, H., Blankenberg, S., Clarke, R., Collins, R., Kim, B.J., McPherson, R., Nieminen, M.S., O'Donnell, C., Schreiber, S., Zalloua, P.A., Zanoni, P, Khetarpal, SA, Larach, DB, Hancock-Cerutti, WF, Rader, DJ, Hypponen, Elina, Biological Psychology, Khetarpal, S, Larach, D, Hancock Cerutti, W, Millar, J, Cuchel, M, Derohannessian, S, Kontush, A, Surendran, P, Saleheen, D, Trompet, S, Wouter Jukema, J, De Craen, A, Deloukas, P, Sattar, N, Ford, I, Packard, C, Majumder, A, Alam, D, Di Angelantonio, E, Abecasis, G, Chowdhury, R, Erdmann, J, Nordestgaard, B, Nielsen, S, Tybjærg Hansen, A, Ruth Frikke Schmidt, N, Kuulasmaa, K, Liu, D, Perola, M, Blankenberg, S, Salomaa, V, Männistö, S, Amouyel, P, Arveiler, D, Ferrieres, J, Möller Nurasyid, M, Ferrario, M, Kee, F, Willer, C, Samani, N, Schunkert, H, Butterworth, A, Howson, J, Peloso, G, Stitziel, N, Danesh, J, Kathiresan, S, Rader, D, Brambilla, P, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine
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Netherlands Twin Register (NTR) ,0301 basic medicine ,Male ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Scavenger Receptors ,DNA Mutational Analysis ,Coronary Disease ,030204 cardiovascular system & hematology ,scavenger receptor ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,High-density lipoprotein ,Receptor ,increased atherosclerosis ,levels of plasma ,Multidisciplinary ,Medicine (all) ,Homozygote ,Scavenger Receptors, Class B ,Middle Aged ,3. Good health ,Cholesterol ,Knockout mouse ,Female ,lipids (amino acids, peptides, and proteins) ,Human ,Risk ,medicine.medical_specialty ,Heterozygote ,HDL ,Proline ,Aged ,Amino Acid Substitution ,Animals ,Cholesterol, HDL ,Genetic Variation ,Humans ,Leucine ,Protein Processing, Post-Translational ,Article ,DNA Mutational Analysi ,Cholesterol, HDL/blood ,Coronary Disease/blood ,Coronary Disease/genetics ,Leucine/genetics ,Proline/genetics ,Scavenger Receptors, Class B/genetics ,Scavenger Receptors, Class B/metabolism ,03 medical and health sciences ,Internal medicine ,medicine ,Scavenger receptor ,Protein Processing ,Animal ,business.industry ,Post-Translational ,Heterozygote advantage ,SCARB1 ,030104 developmental biology ,Endocrinology ,chemistry ,Class B ,business ,Lipoprotein - Abstract
Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a lossof-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant). Zanoni P, Khetarpal SA, Larach DB, Hancock-Cerutti WF, Millar JS, Cuchel M, DerOhannessian S, Kontush A, Surendran P, Saleheen D, Trompet S, Jukema JW, De Craen A, Deloukas P, Sattar N, Ford I, Packard C, Majumder Aa, Alam DS, Di Angelantonio E, Science (New York, N.Y.), 2016, vol. 351, no. 6278, pp. 1166-1171, 2016 Refereed/Peer-reviewed
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- 2016
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21. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts
- Author
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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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- 2013
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