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131 results on '"Day, FR."'

1. Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author: Kentistou, KA, Kaisinger, LR, Stankovic, S, Vaudel, M, Mendes de Oliveira, E, Messina, A, Walters, RG, Liu, X, Busch, AS, Helgason, H, Thompson, DJ, Santoni, F, Petricek, KM, Zouaghi, Y, Huang-Doran, I, Gudbjartsson, DF, Bratland, E, Lin, K, Gardner, EJ, Zhao, Y, Jia, RY, Terao, C, Riggan, MJ, Bolla, MK, Yazdanpanah, M, Yazdanpanah, N, Bradfield, JP, Broer, L, Campbell, A, Chasman, DI, Cousminer, DL, Franceschini, N, Franke, LH, Girotto, G, He, C, Järvelin, M-R, Joshi, PK, Kamatani, Y, Karlsson, R, Luan, J, Lunetta, KL, Mägi, R, Mangino, M, Medland, SE, Meisinger, C, Noordam, R, Nutile, T, Concas, MP, Polašek, O, Porcu, E, Ring, SM, Sala, C, Smith, AV, Tanaka, T, van der Most, PJ, Vitart, V, Wang, CA, Willemsen, G, Zygmunt, M, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Auer, PL, Barnes, CLK, Beckmann, MW, Berrington de Gonzalez, A, Bogdanova, NV, Bojesen, SE, Brenner, H, Buring, JE, Canzian, F, Chang-Claude, J, Couch, FJ, Cox, A, Crisponi, L, Czene, K, Daly, MB, Demerath, EW, Dennis, J, Devilee, P, De Vivo, I, Dörk, T, Dunning, AM, Dwek, M, Eriksson, JG, Fasching, PA, Fernandez-Rhodes, L, Ferreli, L, Fletcher, O, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, González-Neira, A, Grallert, H, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hakonarson, H, Hart, RJ, Hickey, M, Hooning, MJ, Hoppe, R, Hopper, JL, Hottenga, J-J, Hu, FB, Huebner, H, Hunter, DJ, ABCTB Investigators, Jernström, H, John, EM, Karasik, D, Khusnutdinova, EK, Kristensen, VN, Lacey, JV, Lambrechts, D, Launer, LJ, Lind, PA, Lindblom, A, Magnusson, PKE, Mannermaa, A, McCarthy, MI, Meitinger, T, Menni, C, Michailidou, K, Millwood, IY, Milne, RL, Montgomery, GW, Nevanlinna, H, Nolte, IM, Nyholt, DR, Obi, N, O'Brien, KM, Offit, K, Oldehinkel, AJ, Ostrowski, SR, Palotie, A, Pedersen, OB, Peters, A, Pianigiani, G, Plaseska-Karanfilska, D, Pouta, A, Pozarickij, A, Radice, P, Rennert, G, Rosendaal, FR, Ruggiero, D, Saloustros, E, Sandler, DP, Schipf, S, Schmidt, CO, Schmidt, MK, Small, K, Spedicati, B, Stampfer, M, Stone, J, Tamimi, RM, Teras, LR, Tikkanen, E, Turman, C, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Zemel, BS, Zheng, W, van Dijk, KW, Alizadeh, BZ, Bandinelli, S, Boerwinkle, E, Boomsma, DI, Ciullo, M, Chenevix-Trench, G, Cucca, F, Esko, T, Gieger, C, Grant, SFA, Gudnason, V, Hayward, C, Kolčić, I, Kraft, P, Lawlor, DA, Martin, NG, Nøhr, EA, Pedersen, NL, Pennell, CE, Ridker, PM, Robino, A, Snieder, H, Sovio, U, Spector, TD, Stöckl, D, Sudlow, C, Timpson, NJ, Toniolo, D, Uitterlinden, A, Ulivi, S, Völzke, H, Wareham, NJ, Widen, E, Wilson, JF, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Pharoah, PDP, Li, L, Easton, DF, Njølstad, PR, Sulem, P, Murabito, JM, Murray, A, Manousaki, D, Juul, A, Erikstrup, C, Stefansson, K, Horikoshi, M, Chen, Z, Farooqi, IS, Pitteloud, N, Johansson, S, Day, FR, Perry, JRB, Ong, KK, Kentistou, KA, Kaisinger, LR, Stankovic, S, Vaudel, M, Mendes de Oliveira, E, Messina, A, Walters, RG, Liu, X, Busch, AS, Helgason, H, Thompson, DJ, Santoni, F, Petricek, KM, Zouaghi, Y, Huang-Doran, I, Gudbjartsson, DF, Bratland, E, Lin, K, Gardner, EJ, Zhao, Y, Jia, RY, Terao, C, Riggan, MJ, Bolla, MK, Yazdanpanah, M, Yazdanpanah, N, Bradfield, JP, Broer, L, Campbell, A, Chasman, DI, Cousminer, DL, Franceschini, N, Franke, LH, Girotto, G, He, C, Järvelin, M-R, Joshi, PK, Kamatani, Y, Karlsson, R, Luan, J, Lunetta, KL, Mägi, R, Mangino, M, Medland, SE, Meisinger, C, Noordam, R, Nutile, T, Concas, MP, Polašek, O, Porcu, E, Ring, SM, Sala, C, Smith, AV, Tanaka, T, van der Most, PJ, Vitart, V, Wang, CA, Willemsen, G, Zygmunt, M, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Auer, PL, Barnes, CLK, Beckmann, MW, Berrington de Gonzalez, A, Bogdanova, NV, Bojesen, SE, Brenner, H, Buring, JE, Canzian, F, Chang-Claude, J, Couch, FJ, Cox, A, Crisponi, L, Czene, K, Daly, MB, Demerath, EW, Dennis, J, Devilee, P, De Vivo, I, Dörk, T, Dunning, AM, Dwek, M, Eriksson, JG, Fasching, PA, Fernandez-Rhodes, L, Ferreli, L, Fletcher, O, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, González-Neira, A, Grallert, H, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hakonarson, H, Hart, RJ, Hickey, M, Hooning, MJ, Hoppe, R, Hopper, JL, Hottenga, J-J, Hu, FB, Huebner, H, Hunter, DJ, ABCTB Investigators, Jernström, H, John, EM, Karasik, D, Khusnutdinova, EK, Kristensen, VN, Lacey, JV, Lambrechts, D, Launer, LJ, Lind, PA, Lindblom, A, Magnusson, PKE, Mannermaa, A, McCarthy, MI, Meitinger, T, Menni, C, Michailidou, K, Millwood, IY, Milne, RL, Montgomery, GW, Nevanlinna, H, Nolte, IM, Nyholt, DR, Obi, N, O'Brien, KM, Offit, K, Oldehinkel, AJ, Ostrowski, SR, Palotie, A, Pedersen, OB, Peters, A, Pianigiani, G, Plaseska-Karanfilska, D, Pouta, A, Pozarickij, A, Radice, P, Rennert, G, Rosendaal, FR, Ruggiero, D, Saloustros, E, Sandler, DP, Schipf, S, Schmidt, CO, Schmidt, MK, Small, K, Spedicati, B, Stampfer, M, Stone, J, Tamimi, RM, Teras, LR, Tikkanen, E, Turman, C, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Zemel, BS, Zheng, W, van Dijk, KW, Alizadeh, BZ, Bandinelli, S, Boerwinkle, E, Boomsma, DI, Ciullo, M, Chenevix-Trench, G, Cucca, F, Esko, T, Gieger, C, Grant, SFA, Gudnason, V, Hayward, C, Kolčić, I, Kraft, P, Lawlor, DA, Martin, NG, Nøhr, EA, Pedersen, NL, Pennell, CE, Ridker, PM, Robino, A, Snieder, H, Sovio, U, Spector, TD, Stöckl, D, Sudlow, C, Timpson, NJ, Toniolo, D, Uitterlinden, A, Ulivi, S, Völzke, H, Wareham, NJ, Widen, E, Wilson, JF, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Pharoah, PDP, Li, L, Easton, DF, Njølstad, PR, Sulem, P, Murabito, JM, Murray, A, Manousaki, D, Juul, A, Erikstrup, C, Stefansson, K, Horikoshi, M, Chen, Z, Farooqi, IS, Pitteloud, N, Johansson, S, Day, FR, Perry, JRB, and Ong, KK
Abstract: Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.
Published: 2024

2. Genetic insights into biological mechanisms governing human ovarian ageing

Author: Ruth KS, Day FR, Hussain J, Martinez-Marchal A, Aiken CE, Azad A, and Thompson DJ
Subjects: General Economics, Econometrics and Finance
Published: 2022
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3. MC3R links nutritional state to childhood growth and the timing of puberty

Author: Lam BYH, Williamson A, Finer S, Day FR, Tadross JA, A Goncalves Soares, Wade K, Sweeney P, Bedenbaugh MN, Porter DT, Melvin A, Ellacott KLJ, Lippert RN, Buller S, Rosmaninho-Salgado J, Dowsett GKC, Ridley KE, Xu Z, Cimino I, Rimmington D, Rainbow K, Duckett K, Holmqvist S, Khan A, Dai X, Bochukova X, Genes & Health Research Team X, Martin X, Coll X, Rowitch X, Wareham X, van Heel X, Timpson X, Simerly X, Ong X, Cone X, Langenberg X, Perry X, Yeo X, and O'Rahilly X
Subjects: General Economics, Econometrics and Finance
Published: 2022
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4. MC3R links nutritional state to childhood growth and the timing of puberty

Author: Lam, BYH, Williamson, A, Finer, S, Day, FR, Tadross, JA, Gonçalves Soares, A, Wade, K, Sweeney, P, Bedenbaugh, MN, Porter, DT, Melvin, A, Ellacott, KLJ, Lippert, RN, Buller, S, Rosmaninho-Salgado, J, Dowsett, GKC, Ridley, KE, Xu, Z, Cimino, I, Rimmington, D, Rainbow, K, Duckett, K, Holmqvist, S, Khan, A, Dai, X, Bochukova, EG, Genes & Health Research Team, Trembath, RC, Martin, HC, Coll, AP, Rowitch, DH, Wareham, NJ, Van Heel, DA, Timpson, N, Simerly, RB, Ong, KK, Cone, RD, Langenberg, C, Perry, JRB, Yeo, GS, O'Rahilly, S, Lam, BYH [0000-0002-3638-9025], Williamson, A [0000-0002-7599-9301], Finer, S [0000-0002-2684-4653], Day, FR [0000-0003-3789-7651], Tadross, JA [0000-0002-8424-1252], Wade, K [0000-0003-3362-6280], Porter, DT [0000-0002-8042-3251], Cimino, I [0000-0003-1397-5408], Holmqvist, S [0000-0001-6709-6666], Khan, A [0000-0002-5189-6906], Martin, HC [0000-0002-4454-9084], Rowitch, DH [0000-0002-0079-0060], Wareham, NJ [0000-0003-1422-2993], van Heel, DA [0000-0002-0637-2265], Timpson, N [0000-0002-7141-9189], Simerly, RB [0000-0001-5840-0152], Ong, KK [0000-0003-4689-7530], Cone, RD [0000-0003-3333-5651], Langenberg, C [0000-0002-5017-7344], Perry, JRB [0000-0001-6483-3771], Yeo, GS [0000-0001-8823-3615], O'Rahilly, S [0000-0003-2199-4449], and Apollo - University of Cambridge Repository
Subjects: Aged, 80 and over, Male, Menarche, Time Factors, Adolescent, Homozygote, Puberty, Hypothalamus, Nutritional Status, Estrous Cycle, Weight Gain, Melanocortins, Mice, Child Development, Phenotype, Animals, Humans, Female, Sexual Maturation, Insulin-Like Growth Factor I, Child, Receptor, Melanocortin, Type 3
Abstract: The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.
Published: 2021
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5. Genetic insights into biological mechanisms governing human ovarian ageing

Author: Ruth, KS, Day, FR, Hussain, J, Martinez-Marchal, A, Aiken, CE, Azad, A, Thompson, DJ, Knoblochova, L, Abe, H, Tarry-Adkins, JL, Gonzalez, JM, Fontanillas, P, Claringbould, A, Bakker, OB, Sulem, P, Walters, RG, Terao, C, Turon, S, Horikoshi, M, Lin, K, Onland-Moret, NC, Sankar, A, Hertz, EPT, Timshel, PN, Shukla, V, Borup, R, Olsen, KW, Aguilera, P, Ferrer-Roda, M, Huang, Y, Stankovic, S, Timmers, PRHJ, Ahearn, TU, Alizadeh, BZ, Naderi, E, Andrulis, IL, Arnold, AM, Aronson, KJ, Augustinsson, A, Bandinelli, S, Barbieri, CM, Beaumont, RN, Becher, H, Beckmann, MW, Benonisdottir, S, Bergmann, S, Bochud, M, Boerwinkle, E, Bojesen, SE, Bolla, MK, Boomsma, DI, Bowker, N, Brody, JA, Broer, L, Buring, JE, Campbell, A, Campbell, H, Castelao, JE, Catamo, E, Chanock, SJ, Chenevix-Trench, G, Ciullo, M, Corre, T, Couch, FJ, Cox, A, Crisponi, L, Cross, SS, Cucca, F, Czene, K, Smith, GD, de Geus, EJCN, de Mutsert, R, De Vivo, I, Demerath, EW, Dennis, J, Dunning, AM, Dwek, M, Eriksson, M, Esko, T, Fasching, PA, Faul, JD, Ferrucci, L, Franceschini, N, Frayling, TM, Gago-Dominguez, M, Mezzavilla, M, Garcia-Closas, M, Gieger, C, Giles, GG, Grallert, H, Gudbjartsson, DF, Gudnason, V, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hayward, C, He, C, He, W, Heiss, G, Hoffding, MK, Hopper, JL, Hottenga, JJ, Hu, F, Hunter, D, Ikram, MA, Jackson, RD, Joaquim, MDR, John, EM, Joshi, PK, Karasik, D, Kardia, SLR, Kartsonaki, C, Karlsson, R, Kitahara, CM, Kolcic, I, Kooperberg, C, Kraft, P, Kurian, AW, Kutalik, Z, La Bianca, M, LaChance, G, Langenberg, C, Launer, LJ, Laven, JSE, Lawlor, DA, Le Marchand, L, Li, J, Lindblom, A, Lindstrom, S, Lindstrom, T, Linet, M, Liu, Y, Liu, S, Luan, J, Magi, R, Magnusson, PKE, Mangino, M, Mannermaa, A, Marco, B, Marten, J, Martin, NG, Mbarek, H, McKnight, B, Medland, SE, Meisinger, C, Meitinger, T, Menni, C, Metspalu, A, Milani, L, Milne, RL, Montgomery, GW, Mook-Kanamori, DO, Mulas, A, Mulligan, AM, Murray, A, Nalls, MA, Newman, A, Noordam, R, Nutile, T, Nyholt, DR, Olshan, AF, Olsson, H, Painter, JN, Patel, AV, Pedersen, NL, Perjakova, N, Peters, A, Peters, U, Pharoah, PDP, Polasek, O, Porcu, E, Psaty, BM, Rahman, I, Rennert, G, Rennert, HS, Ridker, PM, Ring, SM, Robino, A, Rose, LM, Rosendaal, FR, Rossouw, J, Rudan, I, Rueedi, R, Ruggiero, D, Sala, CF, Saloustros, E, Sandler, DP, Sanna, S, Sawyer, EJ, Sarnowski, C, Schlessinger, D, Schmidt, MK, Schoemaker, MJ, Schraut, KE, Scott, C, Shekari, S, Shrikhande, A, Smith, AV, Smith, BH, Smith, JA, Sorice, R, Southey, MC, Spector, TD, Spinelli, JJ, Stampfer, M, Stoeckl, D, van Meurs, JBJ, Strauch, K, Styrkarsdottir, U, Swerdlow, AJ, Tanaka, T, Teras, LR, Teumer, A, thorsteinsdottir, U, Timpson, NJ, Toniolo, D, Traglia, M, Troester, MA, Truong, T, Tyrrell, J, Uitterlinden, AG, Ulivi, S, Vachon, CM, Vitart, V, Voelker, U, Vollenweider, P, Voelzke, H, Wang, Q, Wareham, NJ, Weinberg, CR, Weir, DR, Wilcox, AN, van Dijk, KW, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wolk, A, Wood, AR, Zhao, W, Zygmunt, M, Chen, Z, Li, L, Franke, L, Burgess, S, Deelen, P, Pers, TH, Grondahl, ML, Andersen, CY, Pujol, A, Lopez-Contreras, AJ, Daniel, JA, Stefansson, K, Chang-Claude, J, van der Schouw, YT, Lunetta, KL, Chasman, DI, Easton, DF, Visser, JA, Ozanne, SE, Namekawa, SH, Solc, P, Murabito, JM, Ong, KK, Hoffmann, ER, Roig, I, Perry, JRB, Ruth, KS, Day, FR, Hussain, J, Martinez-Marchal, A, Aiken, CE, Azad, A, Thompson, DJ, Knoblochova, L, Abe, H, Tarry-Adkins, JL, Gonzalez, JM, Fontanillas, P, Claringbould, A, Bakker, OB, Sulem, P, Walters, RG, Terao, C, Turon, S, Horikoshi, M, Lin, K, Onland-Moret, NC, Sankar, A, Hertz, EPT, Timshel, PN, Shukla, V, Borup, R, Olsen, KW, Aguilera, P, Ferrer-Roda, M, Huang, Y, Stankovic, S, Timmers, PRHJ, Ahearn, TU, Alizadeh, BZ, Naderi, E, Andrulis, IL, Arnold, AM, Aronson, KJ, Augustinsson, A, Bandinelli, S, Barbieri, CM, Beaumont, RN, Becher, H, Beckmann, MW, Benonisdottir, S, Bergmann, S, Bochud, M, Boerwinkle, E, Bojesen, SE, Bolla, MK, Boomsma, DI, Bowker, N, Brody, JA, Broer, L, Buring, JE, Campbell, A, Campbell, H, Castelao, JE, Catamo, E, Chanock, SJ, Chenevix-Trench, G, Ciullo, M, Corre, T, Couch, FJ, Cox, A, Crisponi, L, Cross, SS, Cucca, F, Czene, K, Smith, GD, de Geus, EJCN, de Mutsert, R, De Vivo, I, Demerath, EW, Dennis, J, Dunning, AM, Dwek, M, Eriksson, M, Esko, T, Fasching, PA, Faul, JD, Ferrucci, L, Franceschini, N, Frayling, TM, Gago-Dominguez, M, Mezzavilla, M, Garcia-Closas, M, Gieger, C, Giles, GG, Grallert, H, Gudbjartsson, DF, Gudnason, V, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hayward, C, He, C, He, W, Heiss, G, Hoffding, MK, Hopper, JL, Hottenga, JJ, Hu, F, Hunter, D, Ikram, MA, Jackson, RD, Joaquim, MDR, John, EM, Joshi, PK, Karasik, D, Kardia, SLR, Kartsonaki, C, Karlsson, R, Kitahara, CM, Kolcic, I, Kooperberg, C, Kraft, P, Kurian, AW, Kutalik, Z, La Bianca, M, LaChance, G, Langenberg, C, Launer, LJ, Laven, JSE, Lawlor, DA, Le Marchand, L, Li, J, Lindblom, A, Lindstrom, S, Lindstrom, T, Linet, M, Liu, Y, Liu, S, Luan, J, Magi, R, Magnusson, PKE, Mangino, M, Mannermaa, A, Marco, B, Marten, J, Martin, NG, Mbarek, H, McKnight, B, Medland, SE, Meisinger, C, Meitinger, T, Menni, C, Metspalu, A, Milani, L, Milne, RL, Montgomery, GW, Mook-Kanamori, DO, Mulas, A, Mulligan, AM, Murray, A, Nalls, MA, Newman, A, Noordam, R, Nutile, T, Nyholt, DR, Olshan, AF, Olsson, H, Painter, JN, Patel, AV, Pedersen, NL, Perjakova, N, Peters, A, Peters, U, Pharoah, PDP, Polasek, O, Porcu, E, Psaty, BM, Rahman, I, Rennert, G, Rennert, HS, Ridker, PM, Ring, SM, Robino, A, Rose, LM, Rosendaal, FR, Rossouw, J, Rudan, I, Rueedi, R, Ruggiero, D, Sala, CF, Saloustros, E, Sandler, DP, Sanna, S, Sawyer, EJ, Sarnowski, C, Schlessinger, D, Schmidt, MK, Schoemaker, MJ, Schraut, KE, Scott, C, Shekari, S, Shrikhande, A, Smith, AV, Smith, BH, Smith, JA, Sorice, R, Southey, MC, Spector, TD, Spinelli, JJ, Stampfer, M, Stoeckl, D, van Meurs, JBJ, Strauch, K, Styrkarsdottir, U, Swerdlow, AJ, Tanaka, T, Teras, LR, Teumer, A, thorsteinsdottir, U, Timpson, NJ, Toniolo, D, Traglia, M, Troester, MA, Truong, T, Tyrrell, J, Uitterlinden, AG, Ulivi, S, Vachon, CM, Vitart, V, Voelker, U, Vollenweider, P, Voelzke, H, Wang, Q, Wareham, NJ, Weinberg, CR, Weir, DR, Wilcox, AN, van Dijk, KW, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wolk, A, Wood, AR, Zhao, W, Zygmunt, M, Chen, Z, Li, L, Franke, L, Burgess, S, Deelen, P, Pers, TH, Grondahl, ML, Andersen, CY, Pujol, A, Lopez-Contreras, AJ, Daniel, JA, Stefansson, K, Chang-Claude, J, van der Schouw, YT, Lunetta, KL, Chasman, DI, Easton, DF, Visser, JA, Ozanne, SE, Namekawa, SH, Solc, P, Murabito, JM, Ong, KK, Hoffmann, ER, Roig, I, and Perry, JRB
Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
Published: 2021

6. Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan.

Author: Hollis, B, Day, FR, Busch, AS, Thompson, DJ, Soares, ALG, Timmers, PRHJ, Kwong, A, Easton, DF, Joshi, PK, Timpson, NJ, PRACTICAL Consortium, 23andMe Research Team, Ong, KK, Perry, JRB, Hollis, B, Day, FR, Busch, AS, Thompson, DJ, Soares, ALG, Timmers, PRHJ, Kwong, A, Easton, DF, Joshi, PK, Timpson, NJ, PRACTICAL Consortium, 23andMe Research Team, Ong, KK, and Perry, JRB
Abstract: The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes.
Published: 2020

7. Quality control and conduct of genome-wide association meta-analyses

Author: Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis GR, Absher D, Alavere H, Albrecht E, Allen HL, Almgren P, Amin N, Amouyel P, Anderson D, Arnold AM, Arveiler D, Aspelund T, Asselbergs FW, Assimes TL, Atalay M, Attwood AP, Atwood LD, Bakker SJ, Balkau B, Balmforth AJ, Barlassina C, Barroso I, Basart H, Bauer S, Beckmann JS, Beilby JP, Bennett AJ, Ben Shlomo Y, Bergman RN, Bergmann S, Berndt SI, Biffar R, Di Blasio AM, Boehm BO, Boehnke M, Boeing H, Boerwinkle E, Bolton JL, Bonnefond A, Bonnycastle LL, Boomsma DI, Borecki IB, Bornstein SR, Bouatia Naji N, Boucher G, Bragg Gresham JL, BRAMBILLA, PAOLO, Bruinenberg M, Buchanan TA, Buechler C, Cadby G, Campbell H, Caulfield MJ, Cavalcanti Proença C, CESANA, GIANCARLO, Chanock SJ, Chasman DI, Chen YD, Chines PS, Clegg DJ, Coin L, Collins FS, Connell JM, Cookson W, Cooper MN, Croteau Chonka DC, Cupples LA, Cusi D, Day FR, Day IN, Dedoussis GV, Dei M, Deloukas P, Dermitzakis ET, Dimas AS, Dimitriou M, Dixon AL, Dörr M, van Duijn CM, Ebrahim S, Edkins S, Eiriksdottir G, Eisinger K, Eklund N, Elliott P, Erbel R, Erdmann J, Erdos MR, Eriksson JG, Esko T, Estrada K, Evans DM, de Faire U, Fall T, Farrall M, Feitosa MF, Ferrario MM, Ferreira T, Ferrières J, Fischer K, Fisher E, Fowkes G, Fox CS, Franke L, Franks PW, Fraser RM, Frau F, Frayling T, Freimer NB, Froguel P, Fu M, Gaget S, Ganna A, Gejman PV, Gentilini D, Geus EJ, Gieger C, Gigante B, Gjesing AP, Glazer NL, Goddard ME, Goel A, Grallert H, Gräßler J, Grönberg H, Groop LC, Groves CJ, Gudnason V, Guiducci C, Gustafsson S, Gyllensten U, Hall AS, Hall P, Hallmans G, Hamsten A, Hansen T, Haritunians T, Harris TB, van der Harst P, Hartikainen AL, Hassanali N, Hattersley AT, Havulinna AS, Hayward C, Heard Costa NL, Heath AC, Hebebrand J, Heid IM, den Heijer M, Hengstenberg C, Herzig KH, Hicks AA, Hingorani A, Hinney A, Hirschhorn JN, Hofman A, Holmes CC, Homuth G, Hottenga JJ, Hovingh KG, Hu FB, Hu YJ, Huffman JE, Hui J, Huikuri H, Humphries SE, Hung J, Hunt SE, Hunter D, Hveem K, Hyppönen E, Igl W, Illig T, Ingelsson E, Iribarren C, Isomaa B, Jackson AU, Jacobs KB, James AL, Jansson JO, Jarick I, Jarvelin MR, Jöckel KH, Johansson Å, Johnson T, Jolley J, Jørgensen T, Jousilahti P, Jula A, Justice AE, Kaakinen M, Kähönen M, Kajantie E, Kanoni S, Kao WH, Kaplan LM, Kaplan RC, Kaprio J, Kapur K, Karpe F, Kathiresan S, Kee F, Keinanen Kiukaanniemi SM, Ketkar S, Kettunen J, Khaw KT, Kiemeney LA, Kilpeläinen TO, Kinnunen L, Kivimaki M, Kivmaki M, Van der Klauw MM, Kleber ME, Knowles JW, Koenig W, Kolcic I, Kolovou G, König IR, Koskinen S, Kovacs P, Kraft P, Kraja AT, Kristiansson K, KrjutÅjkov K, Kroemer HK, Krohn JP, Krzelj V, Kuh D, Kulzer JR, Kumari M, Kutalik Z, Kuulasmaa K, Kuusisto J, Kvaloy K, Laakso M, Laitinen JH, Lakka TA, Lamina C, Langenberg C, Lantieri O, Lathrop GM, Launer LJ, Lawlor DA, Lawrence RW, Leach IM, Lecoeur C, Lee SH, Lehtimäki T, Leitzmann MF, Lettre G, Levinson DF, Li G, Li S, Liang L, Lin DY, Lind L, Lindgren CM, Lindström J, Liu J, Liuzzi A, Locke AE, Lokki ML, Loley C, Loos RJ, Lorentzon M, Luan J, Luben RN, Ludwig B, Madden PA, Mägi R, Magnusson PK, Mangino M, Manunta P, Marek D, Marre M, Martin NG, März W, Maschio A, Mathieson I, McArdle WL, McCaroll SA, McCarthy A, McCarthy MI, McKnight B, Medina Gomez C, Medland SE, Meitinger T, Metspalu A, van Meurs JB, Meyre D, Midthjell K, Mihailov E, Milani L, Min JL, Moebus S, Moffatt MF, Mohlke KL, Molony C, Monda KL, Montgomery GW, Mooser V, Morken MA, Morris AD, Morris AP, Mühleisen TW, Müller Nurasyid M, Munroe PB, Musk AW, Narisu N, Navis G, Neale BM, Nelis M, Nemesh J, Neville MJ, Ngwa JS, Nicholson G, Nieminen MS, Njølstad I, Nohr EA, Nolte IM, North KE, Nöthen MM, Nyholt DR, O'Connell JR, Ohlsson C, Oldehinkel AJ, van Ommen GJ, Ong KK, Oostra BA, Ouwehand WH, Palmer CN, Palmer LJ, Palotie A, Paré G, Parker AN, Paternoster L, Pawitan Y, Pechlivanis S, Peden JF, Pedersen NL, Pedersen O, Pellikka N, Peltonen L, Penninx B, Perola M, Perry JR, Person T, Peters A, Peters MJ, Pichler I, Pietiläinen KH, Platou CG, Polasek O, Pouta A, Power C, Pramstaller PP, Preuss M, Price JF, Prokopenko I, Province MA, Psaty BM, Purcell S, Pütter C, Qi L, Quertermous T, Radhakrishnan A, Raitakari O, Randall JC, Rauramaa R, Rayner NW, Rehnberg E, Rendon A, Ridderstråle M, Ridker PM, Ripatti S, Rissanen A, Rivadeneira F, Rivolta C, Robertson NR, Rose LM, Rudan I, Saaristo TE, Sager H, Salomaa V, Samani NJ, Sambrook JG, Sanders AR, Sandholt C, Sanna S, Saramies J, Schadt EE, Scherag A, Schipf S, Schlessinger D, Schreiber S, Schunkert H, Schwarz PE, Scott LJ, Shi J, Shin SY, Shuldiner AR, Shungin D, Signorini S, Silander K, Sinisalo J, Skrobek B, Smit JH, Smith AV, Smith GD, Snieder H, Soranzo N, Sørensen TI, Sovio U, Spector TD, Speliotes EK, Stančáková A, Stark K, Stefansson K, Steinthorsdottir V, Stephens JC, Stirrups K, Stolk RP, Strachan DP, Strawbridge RJ, Stringham HM, Stumvoll M, Surakka I, Swift AJ, Syvanen AC, Tammesoo ML, Teder Laving M, Teslovich TM, Teumer A, Theodoraki EV, Thomson B, Thorand B, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tönjes A, Tregouet DA, Tremoli E, Trip MD, Tuomi T, Tuomilehto J, Tyrer J, Uda M, Uitterlinden AG, Usala G, Uusitupa M, Valle TT, Vandenput L, Vatin V, Vedantam S, de Vegt F, Vermeulen SH, Viikari J, Virtamo J, Visscher PM, Vitart V, Van Vliet Ostaptchouk JV, Voight BF, Vollenweider P, Volpato CB, Völzke H, Waeber G, Waite LL, Wallaschofski H, Walters GB, Wang Z, Wareham NJ, Watanabe RM, Watkins H, Weedon MN, Welch R, Weyant RJ, Wheeler E, White CC, Wichmann HE, Widen E, Wild SH, Willemsen G, Willer CJ, Wilsgaard T, Wilson JF, van Wingerden S, Winkelmann BR, Winkler TW, Witte DR, Witteman JC, Wolffenbuttel BH, Wong A, Wood AR, Workalemahu T, Wright AF, Yang J, Yarnell JW, Zgaga L, Zhao JH, Zillikens MC, Zitting P, Zondervan KT, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis, G, Absher, D, Alavere, H, Albrecht, E, Allen, H, Almgren, P, Amin, N, Amouyel, P, Anderson, D, Arnold, A, Arveiler, D, Aspelund, T, Asselbergs, F, Assimes, T, Atalay, M, Attwood, A, Atwood, L, Bakker, S, Balkau, B, Balmforth, A, Barlassina, C, Barroso, I, Basart, H, Bauer, S, Beckmann, J, Beilby, J, Bennett, A, Ben Shlomo, Y, Bergman, R, Bergmann, S, Berndt, S, Biffar, R, Di Blasio, A, Boehm, B, Boehnke, M, Boeing, H, Boerwinkle, E, Bolton, J, Bonnefond, A, Bonnycastle, L, Boomsma, D, Borecki, I, Bornstein, S, Bouatia Naji, N, Boucher, G, Bragg Gresham, J, Brambilla, P, Bruinenberg, M, Buchanan, T, Buechler, C, Cadby, G, Campbell, H, Caulfield, M, Cavalcanti Proença, C, Cesana, G, Chanock, S, Chasman, D, Chen, Y, Chines, P, Clegg, D, Coin, L, Collins, F, Connell, J, Cookson, W, Cooper, M, Cupples, L, Cusi, D, Day, I, Dedoussis, G, Dei, M, Deloukas, P, Dermitzakis, E, Dimas, A, Dimitriou, M, Dixon, A, Dörr, M, van Duijn, C, Ebrahim, S, Edkins, S, Eiriksdottir, G, Eisinger, K, Eklund, N, Elliott, P, Erbel, R, Erdmann, J, Erdos, M, Eriksson, J, Estrada, K, Evans, D, de Faire, U, Farrall, M, Feitosa, M, Ferrario, M, Ferrières, J, Fischer, K, Fisher, E, Fowkes, G, Fox, C, Franke, L, Franks, P, Fraser, R, Frau, F, Frayling, T, Freimer, N, Froguel, P, Fu, M, Gaget, S, Ganna, A, Gejman, P, Gentilini, D, Geus, E, Gieger, C, Gigante, B, Gjesing, A, Glazer, N, Goddard, M, Goel, A, Grallert, H, Gräßler, J, Grönberg, H, Groop, L, Groves, C, Gudnason, V, Guiducci, C, Gyllensten, U, Hall, A, Hall, P, Hallmans, G, Hamsten, A, Hansen, T, Haritunians, T, Harris, T, van der Harst, P, Hartikainen, A, Hassanali, N, Hattersley, A, Havulinna, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, den Heijer, M, Hengstenberg, C, Herzig, K, Hicks, A, Hingorani, A, Hinney, A, Hirschhorn, J, Hofman, A, Holmes, C, Homuth, G, Hottenga, J, Hovingh, K, Hu, F, Hu, Y, Huffman, J, Hui, J, Huikuri, H, Humphries, S, Hung, J, Hunt, S, Hunter, D, Hveem, K, Hyppönen, E, Igl, W, Illig, T, Ingelsson, E, Iribarren, C, Isomaa, B, Jackson, A, Jacobs, K, James, A, Jansson, J, Jarick, I, Jarvelin, M, Jöckel, K, Johansson, Å, Johnson, T, Jolley, J, Jørgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kähönen, M, Kajantie, E, Kanoni, S, Kao, W, Kaplan, L, Kaplan, R, Kaprio, J, Kapur, K, Karpe, F, Kathiresan, S, Kee, F, Keinanen Kiukaanniemi, S, Ketkar, S, Kettunen, J, Khaw, K, Kiemeney, L, Kinnunen, L, Kivimaki, M, Kivmaki, M, Van der Klauw, M, Kleber, M, Knowles, J, Koenig, W, Kolcic, I, Kolovou, G, König, I, Koskinen, S, Kovacs, P, Kraft, P, Kraja, A, Kristiansson, K, Krjutåjkov, K, Kroemer, H, Krohn, J, Krzelj, V, Kuh, D, Kulzer, J, Kumari, M, Kuulasmaa, K, Kuusisto, J, Kvaloy, K, Laakso, M, Laitinen, J, Lakka, T, Lamina, C, Langenberg, C, Lantieri, O, Lathrop, G, Launer, L, Lawlor, D, Lawrence, R, Leach, I, Lecoeur, C, Lee, S, Lehtimäki, T, Leitzmann, M, Lettre, G, Levinson, D, Li, G, Li, S, Liang, L, Lin, D, Lind, L, Lindgren, C, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Loley, C, Lorentzon, M, Luben, R, Ludwig, B, Madden, P, Magnusson, P, Mangino, M, Manunta, P, Marek, D, Marre, M, Martin, N, März, W, Maschio, A, Mathieson, I, Mcardle, W, Mccaroll, S, Mccarthy, A, Mccarthy, M, Mcknight, B, Medina Gomez, C, Medland, S, Meitinger, T, Metspalu, A, van Meurs, J, Meyre, D, Midthjell, K, Mihailov, E, Milani, L, Min, J, Moebus, S, Moffatt, M, Mohlke, K, Molony, C, Monda, K, Montgomery, G, Mooser, V, Morken, M, Morris, A, Mühleisen, T, Müller Nurasyid, M, Munroe, P, Musk, A, Narisu, N, Navis, G, Neale, B, Nelis, M, Nemesh, J, Neville, M, Ngwa, J, Nicholson, G, Nieminen, M, Njølstad, I, Nohr, E, Nolte, I, North, K, Nöthen, M, Nyholt, D, O'Connell, J, Ohlsson, C, Oldehinkel, A, van Ommen, G, Ong, K, Oostra, B, Ouwehand, W, Palmer, C, Palmer, L, Palotie, A, Paré, G, Parker, A, Paternoster, L, Pawitan, Y, Pechlivanis, S, Peden, J, Pedersen, N, Pedersen, O, Pellikka, N, Peltonen, L, Penninx, B, Perola, M, Perry, J, Person, T, Peters, A, Peters, M, Pichler, I, Pietiläinen, K, Platou, C, Polasek, O, Pouta, A, Power, C, Pramstaller, P, Preuss, M, Price, J, Prokopenko, I, Province, M, Psaty, B, Purcell, S, Pütter, C, Qi, L, Quertermous, T, Radhakrishnan, A, Raitakari, O, Rauramaa, R, Rayner, N, Rehnberg, E, Rendon, A, Ridderstråle, M, Ridker, P, Ripatti, S, Rissanen, A, Rivadeneira, F, Rivolta, C, Robertson, N, Rose, L, Rudan, I, Saaristo, T, Sager, H, Salomaa, V, Samani, N, Sambrook, J, Sanders, A, Sandholt, C, Sanna, S, Saramies, J, Schadt, E, Schipf, S, Schlessinger, D, Schreiber, S, Schunkert, H, Schwarz, P, Scott, L, Shi, J, Shin, S, Shuldiner, A, Shungin, D, Signorini, S, Silander, K, Sinisalo, J, Skrobek, B, Smit, J, Smith, A, Smith, G, Snieder, H, Soranzo, N, Sørensen, T, Sovio, U, Spector, T, Speliotes, E, Stančáková, A, Stark, K, Stefansson, K, Steinthorsdottir, V, Stephens, J, Stirrups, K, Stolk, R, Strachan, D, Strawbridge, R, Stringham, H, Stumvoll, M, Surakka, I, Swift, A, Syvanen, A, Tammesoo, M, Teder Laving, M, Teslovich, T, Teumer, A, Theodoraki, E, Thomson, B, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Timpson, N, Tönjes, A, Tregouet, D, Tremoli, E, Trip, M, Tuomi, T, Tuomilehto, J, Tyrer, J, Uda, M, Uitterlinden, A, Usala, G, Uusitupa, M, Valle, T, Vandenput, L, Vatin, V, de Vegt, F, Vermeulen, S, Viikari, J, Virtamo, J, Visscher, P, Vitart, V, Van Vliet Ostaptchouk, J, Voight, B, Vollenweider, P, Volpato, C, Völzke, H, Waeber, G, Waite, L, Wallaschofski, H, Walters, G, Wang, Z, Wareham, N, Watanabe, R, Watkins, H, Weedon, M, Welch, R, Weyant, R, Wheeler, E, White, C, Wichmann, H, Widen, E, Wild, S, Willemsen, G, Willer, C, Wilsgaard, T, Wilson, J, van Wingerden, S, Winkelmann, B, Witte, D, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Yang, J, Yarnell, J, Zgaga, L, Zhao, J, Zillikens, M, Zitting, P, Zondervan, K, Psychiatry, EMGO - Mental health, Plastic, Reconstructive and Hand Surgery, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Biological Psychology, EMGO+ - Mental Health, Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Abecasis, GR., Absher, D., Alavere, H., Albrecht, E., Allen, HL., Almgren, P., Amin, N., Amouyel, P., Anderson, D., Arnold, AM., Arveiler, D., Aspelund, T., Asselbergs, FW., Assimes, TL., Atalay, M., Attwood, AP., Atwood, LD., Bakker, SJ., Balkau, B., Balmforth, AJ., Barlassina, C., Barroso£££Inês£££ I., Basart, H., Bauer, S., Beckmann, JS., Beilby, JP., Bennett, AJ., Ben-Shlomo, Y., Bergman, RN., Bergmann, S., Berndt, SI., Biffar, R., Di Blasio AM., Boehm, BO., Boehnke, M., Boeing, H., Boerwinkle, 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P., Fu, M., Gaget, S., Ganna, A., Gejman, PV., Gentilini, D., Geus, EJ., Gieger, C., Gigante, B., Gjesing, AP., Glazer, NL., Goddard, ME., Goel, A., Grallert, H., Gräßler, J., Grönberg, H., Groop, LC., Groves, CJ., Gudnason, V., Guiducci, C., Gustafsson, S., Gyllensten, U., Hall, AS., Hall, P., Hallmans, G., Hamsten, A., Hansen, T., Haritunians, T., Harris, TB., van der Harst, P., Hartikainen, AL., Hassanali, N., Hattersley, AT., Havulinna, AS., Hayward, C., Heard-Costa, NL., Heath, AC., Hebebrand, J., Heid, IM., den Heijer, M., Hengstenberg, C., Herzig, KH., Hicks, AA., Hingorani, A., Hinney, A., Hirschhorn, JN., Hofman, A., Holmes, CC., Homuth, G., Hottenga, JJ., Hovingh, KG., Hu, FB., Hu, YJ., Huffman, JE., Hui, J., Huikuri, H., Humphries, SE., Hung, J., Hunt, SE., Hunter, D., Hveem, K., Hyppönen, E., Igl, W., Illig, T., Ingelsson, E., Iribarren, C., Isomaa, B., Jackson, AU., Jacobs, KB., James, AL., Jansson, JO., Jarick, I., Jarvelin, MR., Jöckel, KH., Johansson£££Åsa£££ Å., 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Parker, AN., Paternoster, L., Pawitan, Y., Pechlivanis, S., Peden, JF., Pedersen, NL., Pedersen, O., Pellikka, N., Peltonen, L., Penninx, B., Perola, M., Perry, JR., Person, T., Peters, A., Peters, MJ., Pichler, I., Pietiläinen, KH., Platou, CG., Polasek, O., Pouta, A., Power, C., Pramstaller, PP., Preuss, M., Price, JF., Prokopenko, I., Province, MA., Psaty, BM., Purcell, S., Pütter, C., Qi, L., Quertermous, T., Radhakrishnan, A., Raitakari, O., Randall, JC., Rauramaa, R., Rayner, NW., Rehnberg, E., Rendon, A., Ridderstråle, M., Ridker, PM., Ripatti, S., Rissanen, A., Rivadeneira, F., Rivolta, C., Robertson, NR., Rose, LM., Rudan, I., Saaristo, TE., Sager, H., Salomaa, V., Samani, NJ., Sambrook, JG., Sanders, AR., Sandholt, C., Sanna, S., Saramies, J., Schadt, EE., Scherag, A., Schipf, S., Schlessinger, D., Schreiber, S., Schunkert, H., Schwarz, PE., Scott, LJ., Shi, J., Shin, SY., Shuldiner, AR., Shungin, D., Signorini, S., Silander, K., Sinisalo, J., Skrobek, B., Smit, JH., Smith, AV., Smith, GD., Snieder, H., Soranzo, N., Sørensen, TI., Sovio, U., Spector, TD., Speliotes, EK., Stančáková, A., Stark, K., Stefansson, K., Steinthorsdottir, V., Stephens, JC., Stirrups, K., Stolk, RP., Strachan, DP., Strawbridge, RJ., Stringham, HM., Stumvoll, M., Surakka, I., Swift, AJ., Syvanen, AC., Tammesoo, ML., Teder-Laving, M., Teslovich, TM., Teumer, A., Theodoraki, EV., Thomson, B., Thorand, B., Thorleifsson, G., Thorsteinsdottir, U., Timpson, NJ., Tönjes, A., Tregouet, DA., Tremoli, E., Trip, MD., Tuomi, T., Tuomilehto, J., Tyrer, J., Uda, M., Uitterlinden, AG., Usala, G., Uusitupa, M., Valle, TT., Vandenput, L., Vatin, V., Vedantam, S., de Vegt, F., Vermeulen, SH., Viikari, J., Virtamo, J., Visscher, PM., Vitart, V., Van Vliet-Ostaptchouk JV., Voight, BF., Vollenweider, P., Volpato, CB., Völzke, H., Waeber, G., Waite, LL., Wallaschofski, H., Walters, GB., Wang, Z., Wareham, NJ., Watanabe, RM., Watkins, H., Weedon, MN., Welch, R., Weyant, RJ., Wheeler, E., White, CC., Wichmann, HE., Widen, E., Wild, SH., Willemsen, G., Willer, CJ., Wilsgaard, T., Wilson, JF., van Wingerden, S., Winkelmann, BR., Winkler, TW., Witte, DR., Witteman, JC., Wolffenbuttel, BH., Wong, A., Wood, AR., Workalemahu, T., Wright, AF., Yang, J., Yarnell, JW., Zgaga, L., Zhao, JH., Zillikens, MC., Zitting, P., and Zondervan, KT.
Subjects: Quality Control, Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, media_common.quotation_subject, quality control, GWAMAS, Control (management), Medizin, Genome-wide association study, Biology, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Software, SDG 17 - Partnerships for the Goals, Meta-Analysis as Topic, Comparable size, Quality (business), 030304 developmental biology, media_common, Protocol (science), 0303 health sciences, business.industry, Software package, Data science, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Genome-Wide Association Study/methods, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], quality control, genome-wide association meta-analyses, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Item does not contain fulltext Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.
Published: 2014
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8. Defining the role of common variation in the genomic and biological architecture of adult human height

Author: 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, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, Van Der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Speliotes, E, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Boehnke, M, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, Van Duijn, C, Franke, L, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, 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., 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., Kuller, L., Psychiatry, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Wood, Ar, Pers, Th, Chu, Ay, Buchkovich, Ml, CROTEAU CHONKA, Dc, Day, Fr, Jackson, Au, Locke, Ae, Randall, Jc, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Zhao, Jh, Ehret, Gb, Feitosa, Mf, Fraser, Rm, Justice, Ae, Kleber, Me, Lui, Jc, MATEO LEACH, I, MEDINA GOMEZ, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Strawbridge, Rj, Sung, Yj, VAN DER LAAN, Sw, VAN SETTEN, J, VAN VLIET OSTAPTCHOUK, Jv, Arnlöv, J, Arscott, Gm, Bennett, Aj, Bolton, Jl, Boyd, Ha, Buckley, Bm, Caspersen, Ih, CLAUDI BOEHM, S, Daw, Ew, DE JONG, Pa, Denny, Jc, DHONUKSHE RUTTEN, R, Garcia, Me, Grammer, Tb, DE GROOT, Lc, Groves, Cj, Hartman, Ca, HEARD COSTA, Nl, Henders, Ak, Hillege, Hl, Hlatky, Ma, HOUWING 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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., 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., Stancakova 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., Arnlov J., Arscott G.M., Bandinelli S., Barrett A., Bellis C., Bennett A.J., Berne C., Bluher M., Bolton J.L., Bottcher Y., Boyd H.A., Bruinenberg M., Buckley B.M., Buyske S., 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.F., Dorr M., Eklund N., Eury E., Folkersen L., Garcia M.E., Geller F., Giedraitis V., Go A.S., Grallert H., Grammer T.B., Grassler J., Gronberg H., De Groot L.C.P.G.M., Groves C.J., Haessler 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., Jeff J., Johansen B., Johansson A., Jolley J., Juliusdottir T., Junttila J., Kho A.N., Kinnunen L., Klopp N., Kocher T., Kratzer W., Lichtner P., Lind L., Lindstrom J., Lobbens S., Lorentzon M., Lu Y., Lyssenko V., Magnusson P.K.E., 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., Muller G., Muller-Nurasyid M., Musk A.W., Narisu N., Nauck M., Nolte I.M., Nothen 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., Schunkert H., 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., Sundstrom J., Swertz M.A., Syvanen A.-C., Tayo B.O., Thorleifsson G., Tyrer J.P., Van Dijk S., Van Schoor N.M., Van Der Velde N., Van Heemst D., Van Oort F.V.A., 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.L., Beilby J., Bergman R.N., Bergmann S., Biffar R., Blangero J., Boomsma D.I., Bornstein S.R., Bovet P., Brambilla P., Brown M.J., Campbell H., Caulfield M.J., Chakravarti A., Collins R., Collins F.S., Crawford D.C., Cupples L.A., Danesh J., De Faire U., Den Ruijter H.M., Erbel R., Erdmann J., Eriksson J.G., Farrall M., Ferrannini E., Ferrieres J., Ford I., Forouhi N.G., Forrester T., Gansevoort R.T., Gejman P.V., Gieger C., Golay A., Gottesman O., Gudnason V., Gyllensten U., Haas D.W., Hall A.S., Harris T.B., Hattersley A.T., Heath A.C., Hengstenberg C., Hicks A.A., Hindorff L.A., Hingorani A.D., Hofman A., Hovingh G.K., Humphries S.E., Hunt S.C., Hypponen E., Jacobs K.B., Jarvelin M.-R., Jousilahti P., Jula A.M., Kaprio J., Kastelein J.J.P., Kayser M., Kee F., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kooner J.S., Kooperberg C., Koskinen S., Kovacs P., Kraja A.T., Kumari M., Kuusisto J., Lakka T.A., Langenberg C., Le Marchand L., Lehtimaki T., Lupoli S., Madden P.A.F., Mannisto S., Manunta P., Marette A., Matise T.C., McKnight B., Meitinger T., Moll F.L., Montgomery G.W., Morris A.D., Morris A.P., Murray J.C., Nelis M., Ohlsson C., Oldehinkel A.J., Ong K.K., Ouwehand W.H., Pasterkamp G., Peters A., Pramstaller P.P., Price J.F., Qi L., Raitakari O.T., Rankinen T., Rao D.C., Rice T.K., Ritchie M., Rudan I., Salomaa V., Samani N.J., Saramies J., Sarzynski M.A., Schwarz P.E.H., Sebert S., Sever P., Shuldiner A.R., Sinisalo J., Steinthorsdottir V., Stolk R.P., Tardif J.-C., Tonjes A., Tremblay A., Tremoli E., Virtamo J., Vohl M.-C., Amouyel P., Asselbergs F.W., Assimes T.L., Bochud M., Boehm B.O., Boerwinkle E., Bottinger E.P., Bouchard C., Cauchi S., Chambers J.C., Chanock S.J., Cooper R.S., De Bakker P.I.W., Dedoussis G., Ferrucci L., Franks P.W., Froguel P., Groop L.C., Haiman C.A., Hamsten A., Hayes M.G., Hui J., Hunter D.J., Hveem K., Jukema J.W., Kaplan R.C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N.G., Marz W., Melbye M., Moebus S., Munroe P.B., Njolstad I., Oostra B.A., Palmer C.N.A., Pedersen N.L., Perola M., Perusse L., Peters U., 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., Snieder H., Spector T.D., Strauch K., Stumvoll M., Tuomilehto J., Uusitupa M., Van Der Harst P., Volzke H., Walker M., Wareham N.J., Watkins H., Wichmann H.-E., Wilson J.F., Zanen P., Deloukas P., Heid I.M., Lindgren C.M., Mohlke K.L., Speliotes E.K., Thorsteinsdottir U., 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., Stefansson K., Uitterlinden A.G., Van Duijn C.M., Franke L., Willer C.J., 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.
Subjects: 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.
Published: 2014
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9. The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects

Author: Middeldorp, CM, Mahajan, A, Horikoshi, M, Robertson, NR, Beaumont, RN, Bradfield, JP, Bustamante, M, Cousminer, DL, Day, FR, De Silva, NM, Guxens, M, Mook-Kanamori, DO, St Pourcain, B, Warrington, NM, Adair, LS, Ahlqvist, E, Ahluwalia, TS, Almgren, P, Ang, W, Atalay, M, Auvinen, J, Bartels, M, Beckmann, JS, Bilbao, JR, Bond, T, Borja, JB, Cavadino, A, Charoen, P, Chen, Z, Coin, L, Cooper, C, Curtin, JA, Custovic, A, Das, S, Davies, GE, Dedoussis, GV, Duijts, L, Eastwood, PR, Eliasen, AU, Elliott, P, Eriksson, JG, Estivill, X, Fadista, J, Fedko, IO, Frayling, TM, Gaillard, R, Gauderman, WJ, Geller, F, Gilliland, F, Gilsanz, V, Granell, R, Grarup, N, Groop, L, Hadley, D, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayes, MG, Hebebrand, J, Heinrich, J, Helgeland, O, Henders, AK, Henderson, J, Henriksen, TB, Hirschhorn, JN, Hivert, M-F, Hocher, B, Holloway, JW, Holt, P, Hottenga, J-J, Hypponen, E, Iniguez, C, Johansson, S, Jugessur, A, Kahonen, M, Kalkwarf, HJ, Kaprio, J, Karhunen, V, Kemp, JP, Kerkhof, M, Koppelman, GH, Korner, A, Kotecha, S, Kreiner-Moller, E, Kulohoma, B, Kumar, A, Kutalik, Z, Lahti, J, Lappe, JM, Larsson, H, Lehtimaki, T, Lewin, AM, Li, J, Lichtenstein, P, Lindgren, CM, Lindi, V, Linneberg, A, Liu, X, Liu, J, Lowe, WL, Lundstrom, S, Lyytikainen, L-P, Ma, RCW, Mace, A, Magi, R, Magnus, P, Mamun, AA, Mannikko, M, Martin, NG, Mbarek, H, McCarthy, NS, Medland, SE, Melbye, M, Melen, E, Mohlke, KL, Monnereau, C, Morgen, CS, Morris, AP, Murray, JC, Myhre, R, Najman, JM, Nivard, MG, Nohr, EA, Nolte, IM, Ntalla, I, O'Reilly, P, Oberfield, SE, Oken, E, Oldehinkel, AJ, Pahkala, K, Palviainen, T, Panoutsopoulou, K, Pedersen, O, Pennell, CE, Pershagen, G, Pitkanen, N, Plomin, R, Power, C, Prasad, RB, Prokopenko, I, Pulkkinen, L, Raikkonen, K, Raitakari, OT, Reynolds, RM, Richmond, RC, Rivadeneira, F, Rodriguez, A, Rose, RJ, Salem, R, Santa-Marina, L, Saw, S-M, Schnurr, TM, Scott, JG, Selzam, S, Shepherd, JA, Simpson, A, Skotte, L, Sleiman, PMA, Snieder, H, Sorensen, TIA, Standl, M, Steegers, EAP, Strachan, DP, Straker, L, Strandberg, T, Taylor, M, Teo, Y-Y, Thiering, E, Torrent, M, Tyrrell, J, Uitterlinden, AG, van Beijsterveldt, T, van der Most, PJ, van Duijn, CM, Viikari, J, Vilor-Tejedor, N, Vogelezang, S, Vonk, JM, Vrijkotte, TGM, Vuoksimaa, E, Wang, CA, Watkins, WJ, Wichmann, H-E, Willemsen, G, Williams, GM, Wilson, JF, Wray, NR, Xu, S, Xu, C-J, Yaghootkar, H, Yi, L, Zafarmand, MH, Zeggini, E, Zemel, BS, Hinney, A, Lakka, TA, Whitehouse, AJO, Sunyer, J, Widen, EE, Feenstra, B, Sebert, S, Jacobsson, B, Njolstad, PR, Stoltenberg, C, Smith, GD, Lawlor, DA, Paternoster, L, Timpson, NJ, Ong, KK, Bisgaard, H, Bonnelykke, K, Jaddoe, VWV, Tiemeier, H, Jarvelin, M-R, Evans, DM, Perry, JRB, Grant, SFA, Boomsma, DI, Freathy, RM, McCarthy, MI, Felix, JF, Middeldorp, CM, Mahajan, A, Horikoshi, M, Robertson, NR, Beaumont, RN, Bradfield, JP, Bustamante, M, Cousminer, DL, Day, FR, De Silva, NM, Guxens, M, Mook-Kanamori, DO, St Pourcain, B, Warrington, NM, Adair, LS, Ahlqvist, E, Ahluwalia, TS, Almgren, P, Ang, W, Atalay, M, Auvinen, J, Bartels, M, Beckmann, JS, Bilbao, JR, Bond, T, Borja, JB, Cavadino, A, Charoen, P, Chen, Z, Coin, L, Cooper, C, Curtin, JA, Custovic, A, Das, S, Davies, GE, Dedoussis, GV, Duijts, L, Eastwood, PR, Eliasen, AU, Elliott, P, Eriksson, JG, Estivill, X, Fadista, J, Fedko, IO, Frayling, TM, Gaillard, R, Gauderman, WJ, Geller, F, Gilliland, F, Gilsanz, V, Granell, R, Grarup, N, Groop, L, Hadley, D, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayes, MG, Hebebrand, J, Heinrich, J, Helgeland, O, Henders, AK, Henderson, J, Henriksen, TB, Hirschhorn, JN, Hivert, M-F, Hocher, B, Holloway, JW, Holt, P, Hottenga, J-J, Hypponen, E, Iniguez, C, Johansson, S, Jugessur, A, Kahonen, M, Kalkwarf, HJ, Kaprio, J, Karhunen, V, Kemp, JP, Kerkhof, M, Koppelman, GH, Korner, A, Kotecha, S, Kreiner-Moller, E, Kulohoma, B, Kumar, A, Kutalik, Z, Lahti, J, Lappe, JM, Larsson, H, Lehtimaki, T, Lewin, AM, Li, J, Lichtenstein, P, Lindgren, CM, Lindi, V, Linneberg, A, Liu, X, Liu, J, Lowe, WL, Lundstrom, S, Lyytikainen, L-P, Ma, RCW, Mace, A, Magi, R, Magnus, P, Mamun, AA, Mannikko, M, Martin, NG, Mbarek, H, McCarthy, NS, Medland, SE, Melbye, M, Melen, E, Mohlke, KL, Monnereau, C, Morgen, CS, Morris, AP, Murray, JC, Myhre, R, Najman, JM, Nivard, MG, Nohr, EA, Nolte, IM, Ntalla, I, O'Reilly, P, Oberfield, SE, Oken, E, Oldehinkel, AJ, Pahkala, K, Palviainen, T, Panoutsopoulou, K, Pedersen, O, Pennell, CE, Pershagen, G, Pitkanen, N, Plomin, R, Power, C, Prasad, RB, Prokopenko, I, Pulkkinen, L, Raikkonen, K, Raitakari, OT, Reynolds, RM, Richmond, RC, Rivadeneira, F, Rodriguez, A, Rose, RJ, Salem, R, Santa-Marina, L, Saw, S-M, Schnurr, TM, Scott, JG, Selzam, S, Shepherd, JA, Simpson, A, Skotte, L, Sleiman, PMA, Snieder, H, Sorensen, TIA, Standl, M, Steegers, EAP, Strachan, DP, Straker, L, Strandberg, T, Taylor, M, Teo, Y-Y, Thiering, E, Torrent, M, Tyrrell, J, Uitterlinden, AG, van Beijsterveldt, T, van der Most, PJ, van Duijn, CM, Viikari, J, Vilor-Tejedor, N, Vogelezang, S, Vonk, JM, Vrijkotte, TGM, Vuoksimaa, E, Wang, CA, Watkins, WJ, Wichmann, H-E, Willemsen, G, Williams, GM, Wilson, JF, Wray, NR, Xu, S, Xu, C-J, Yaghootkar, H, Yi, L, Zafarmand, MH, Zeggini, E, Zemel, BS, Hinney, A, Lakka, TA, Whitehouse, AJO, Sunyer, J, Widen, EE, Feenstra, B, Sebert, S, Jacobsson, B, Njolstad, PR, Stoltenberg, C, Smith, GD, Lawlor, DA, Paternoster, L, Timpson, NJ, Ong, KK, Bisgaard, H, Bonnelykke, K, Jaddoe, VWV, Tiemeier, H, Jarvelin, M-R, Evans, DM, Perry, JRB, Grant, SFA, Boomsma, DI, Freathy, RM, McCarthy, MI, and Felix, JF
Abstract: The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Published: 2019

10. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals

Author: Lee, JJ, Wedow, R, Okbay, A, Kong, E, Maghzian, O, Zacher, M, Tuan Anh, N-V, Bowers, P, Sidorenko, J, Linner, RK, Fontana, MA, Kundu, T, Lee, C, Li, H, Li, R, Royer, R, Timshel, PN, Walters, RK, Willoughby, EA, Yengo, L, Alver, M, Bao, Y, Clark, DW, Day, FR, Furlotte, NA, Joshi, PK, Kemper, KE, Kleinman, A, Langenberg, C, Magi, R, Trampush, JW, Verma, SS, Wu, Y, Lam, Mei, Zhao, JH, Zheng, Z, Boardman, JD, Campbell, H, Freese, J, Harris, KM, Hayward, C, Herd, P, Kumari, M, Lencz, T, Luan, JA, Malhotra, AK, Metspalu, A, Milani, L, Ong, KK, Perry, JRB, Porteous, DJ, Ritchie, MD, Smart, MC, Smith, BH, Tung, JY, Wareham, NJ, Wilson, JF, Beauchamp, JP, Conley, DC, Esko, T, Lehrer, SF, Magnusson, PKE, Oskarsson, S, Pers, TH, Robinson, MR, Thom, K, Watson, C, Chabris, CF, Meyer, MN, Laibson, DI, Yang, Jiaqi, Johannesson, M, Koellinger, PD, Turley, P, Visscher, PM, Benjamin, DJ, Cesarini, D, Lee, JJ, Wedow, R, Okbay, A, Kong, E, Maghzian, O, Zacher, M, Tuan Anh, N-V, Bowers, P, Sidorenko, J, Linner, RK, Fontana, MA, Kundu, T, Lee, C, Li, H, Li, R, Royer, R, Timshel, PN, Walters, RK, Willoughby, EA, Yengo, L, Alver, M, Bao, Y, Clark, DW, Day, FR, Furlotte, NA, Joshi, PK, Kemper, KE, Kleinman, A, Langenberg, C, Magi, R, Trampush, JW, Verma, SS, Wu, Y, Lam, Mei, Zhao, JH, Zheng, Z, Boardman, JD, Campbell, H, Freese, J, Harris, KM, Hayward, C, Herd, P, Kumari, M, Lencz, T, Luan, JA, Malhotra, AK, Metspalu, A, Milani, L, Ong, KK, Perry, JRB, Porteous, DJ, Ritchie, MD, Smart, MC, Smith, BH, Tung, JY, Wareham, NJ, Wilson, JF, Beauchamp, JP, Conley, DC, Esko, T, Lehrer, SF, Magnusson, PKE, Oskarsson, S, Pers, TH, Robinson, MR, Thom, K, Watson, C, Chabris, CF, Meyer, MN, Laibson, DI, Yang, Jiaqi, Johannesson, M, Koellinger, PD, Turley, P, Visscher, PM, Benjamin, DJ, and Cesarini, D
Published: 2018

11. Biological interpretation of genome-wide association studies using predicted gene functions

Author: Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L, 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, 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 E, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, 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, Ärnlöv 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 A, 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, 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 I, Bornstein SR, Bovet P, BRAMBILLA, PAOLO, 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 E, 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, 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, Thorsteinsdottir U, Barroso I, Fox CS, North KE, Strachan DP, Beckmann JS, Berndt SI, Borecki IB, McCarthy MI, Metspalu A, Stefansson K, Uitterlinden AG, van Duijn CM, Willer CJ, Price AL, Lettre G, Loos RJ, Weedon MN, Ingelsson E, O'Connell JR, Abecasis GR, Chasman DI, Goddard ME, Visscher PM, Frayling T.M., 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), Stem Cell Aging Leukemia and Lymphoma (SALL), Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Wood, AR., Esko, T., Yang, J., Vedantam, S., Pers, TH., Gustafsson, S., Chu, AY., Estrada, K., Luan£££Jian'an£££ J., Kutalik£££Zoltán£££ 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., 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Garcia, ME., Geller, F., Giedraitis, V., Go, AS., Grallert, H., Grammer, TB., Gräßler, J., Grönberg, H., de Groot LC., Groves, CJ., Haessler, J., 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£££Åsa£££ 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, I., 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, E., Ferrières, J., Ford, I., Forouhi, 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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., 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£££Inês£££ 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, TM., Clinicum, Jaakko Kaprio / Principal Investigator, Department of Public Health, Institute for Molecular Medicine Finland, Genetic Epidemiology, Pers, T, Karjalainen, J, Chan, Y, Westra, H, Wood, A, Yang, J, Lui, J, Vedantam, S, Gustafsson, S, Esko, T, Frayling, T, Speliotes, E, Boehnke, M, Raychaudhuri, S, Fehrmann, R, Hirschhorn, J, Franke, L, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Ferreira, T, Jackson, A, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, 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, E, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Mateo 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, A, 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, 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, I, 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, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, van Duijn, C, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Pers, Th, Karjalainen, Jm, Westra, Hj, Wood, Ar, Lui, Jc, Speliotes, Ek, Hirschhorn, Jn, and Faculty of Health Sciences
Subjects: Cell type, Candidate gene, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, LOCI, General Physics and Astronomy, Genome-wide association study, Disease, Computational biology, Biology, Research Support, General Biochemistry, Genetics and Molecular Biology, Article, DISEASE, N.I.H, CANDIDATE GENES, Genome-Wide Association Study/methods, Software, HEIGHT, Research Support, N.I.H., Extramural, Genetics, Journal Article, NETWORK, Non-U.S. Gov't, Gene, COMMON, Intramural, ARCHITECTURE, Biochemistry, Genetics and Molecular Biology (all), Multidisciplinary, IDENTIFICATION, ta1184, Research Support, Non-U.S. Gov't, Gene sets, Extramural, General Chemistry, ta3121, Research Support, N.I.H., Intramural, Phenotype, 3142 Public health care science, environmental and occupational health, Biological sciences, DATA SETS, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Identification (biology), INTEGRATION, Genome-Wide Association Study
Abstract: Article, The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes., published version, http://purl.org/eprint/status/PeerReviewed
Published: 2015
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12. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

Author: Willems, SM, Wright, DJ, Day, FR, Trajanoska, K, Joshi, PK, Morris, JA, Matteini, AM, Garton, FC, Grarup, N, Oskolkov, N, Thalamuthu, A, Mangino, M, Liu, J, Demirkan, A, Lek, M, Xu, L, Wang, G, Oldmeadow, C, Gaulton, KJ, Lotta, LA, Miyamoto-Mikami, E, Rivas, MA, White, T, Loh, P-R, Aadahl, M, Amin, N, Attia, JR, Austin, K, Benyamin, B, Brage, S, Cheng, Y-C, Cięszczyk, P, Derave, W, Eriksson, K-F, Eynon, N, Linneberg, A, Lucia, A, Massidda, M, Mitchell, BD, Miyachi, M, Murakami, H, Padmanabhan, S, Pandey, A, Papadimitriou, I, Rajpal, DK, Sale, C, Schnurr, TM, Sessa, F, Shrine, N, Tobin, MD, Varley, I, Wain, LV, Wray, NR, Lindgren, CM, MacArthur, DG, Waterworth, DM, McCarthy, MI, Pedersen, O, Khaw, K-T, Kiel, DP, Oei, L, Zheng, H-F, Forgetta, V, Leong, A, Ahmad, OS, Laurin, C, Mokry, LE, Ross, S, Elks, CE, Bowden, J, Warrington, NM, Murray, A, Ruth, KS, Tsilidis, KK, Medina-Gómez, C, Estrada, K, Bis, JC, Chasman, DI, Demissie, S, Enneman, AW, Hsu, Y-H, Ingvarsson, T, Kähönen, M, Kammerer, C, Lacroix, AZ, Li, G, Liu, C-T, Liu, Y, Lorentzon, M, Mägi, R, Mihailov, E, Milani, L, Moayyeri, A, Nielson, CM, Sham, PC, Siggeirsdotir, K, Sigurdsson, G, Stefansson, K, Trompet, S, Thorleifsson, G, Vandenput, L, van der Velde, N, Viikari, J, Xiao, S-M, Zhao, JH, Evans, DS, Cummings, SR, Cauley, J, Duncan, EL, de Groot, LCPGM, Esko, T, Gudnason, V, Harris, TB, Jackson, RD, Jukema, JW, Ikram, AMA, Karasik, D, Kaptoge, S, Kung, AWC, Lehtimäki, T, Lyytikäinen, L-P, Lips, P, Luben, R, Metspalu, A, van Meurs, JBJ, Minster, RL, Orwoll, E, Oei, E, Psaty, BM, Raitakari, OT, Ralston, SW, Ridker, PM, Robbins, JA, Smith, AV, Styrkarsdottir, U, Tranah, GJ, Thorstensdottir, U, Uitterlinden, AG, Zmuda, J, Zillikens, MC, Ntzani, EE, Evangelou, E, Ioannidis, JPA, Evans, DM, Ohlsson, C, Pitsiladis, Y, Fuku, N, Franks, PW, North, KN, van Duijn, CM, Mather, KA, Hansen, T, Hansson, O, Spector, T, Murabito, JM, Richards, JB, Rivadeneira, F, Langenberg, C, Perry, JRB, Wareham, NJ, Scott, RA, Willems, Sara M, Wright, Daniel J, Day, Felix R, Trajanoska, Katerina, Benyamin, Beben, Scott, Robert A, GEFOS Anytype Fracture Consortium, Wright, Daniel [0000-0003-3983-2093], Day, Felix [0000-0003-3789-7651], White, Thomas [0000-0001-8456-0803], Brage, Soren [0000-0002-1265-7355], Khaw, Kay-Tee [0000-0002-8802-2903], Langenberg, Claudia [0000-0002-5017-7344], Perry, John [0000-0001-6483-3771], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Epidemiology, and Internal Medicine
Subjects: Male, Genome-wide association study, VARIANTS, Physical strength, DISEASE, Grip strength, 0302 clinical medicine, Neoplasm Proteins/genetics, GENETIC INFLUENCES, European Continental Ancestry Group/genetics, Aetiology, education.field_of_study, Hand Strength, Deporte, 3. Good health, Neoplasm Proteins, muscular fitness, Science & Technology - Other Topics, Medical genetics, medicine.medical_specialty, Science, 1.1 Normal biological development and functioning, European Continental Ancestry Group, ta3111, Article, White People, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, FRACTURES, Genetics, Humans, GENOME-WIDE ASSOCIATION, Genetik, Polymorphism, education, METAANALYSIS, Aged, VLAG, Global Nutrition, Wereldvoeding, Science & Technology, ta1184, Prevention, Hand/physiology, Biology and Life Sciences, INSTRUMENTS, Hand, GEFOS Any-Type of Fracture Consortium, Nuclear Proteins/genetics, Genetics, Population, 030104 developmental biology, Genetic Loci, 030217 neurology & neurosurgery, 0301 basic medicine, Transforming Growth Factor alpha/genetics, General Physics and Astronomy, Bioinformatics, GROWTH-FACTOR-ALPHA, Cohort Studies, Medicine and Health Sciences, 2.1 Biological and endogenous factors, ta315, Multidisciplinary, Nuclear Proteins, Single Nucleotide, Middle Aged, Multidisciplinary Sciences, MENDELIAN RANDOMIZATION, SKELETAL-MUSCLE, Female, Medical Genetics, Adult, Population, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Underpinning research, Hand strength, MD Multidisciplinary, Mendelian randomization, medicine, Life Science, Membrane Proteins/genetics, Deportes, Medicinsk genetik, Repressor Proteins/genetics, Whites, Actins/genetics, Membrane Proteins, General Chemistry, Transforming Growth Factor alpha, Genética, Actins, United Kingdom, Repressor Proteins, Good Health and Well Being, Exercise Physiology and nutrition, Musculoskeletal, genome-wide association, Genome-Wide Association Study
Abstract: Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P, Hand grip strength as a proxy of muscular fitness is a clinical predictor of mortality and morbidity. In a large-scale GWA study, the authors find 16 robustly associated genetic loci that highlight roles in muscle fibre structure and function, neuronal maintenance and nervous system signal transduction.
Published: 2017
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13. Physical and neurobehavioral determinants of reproductive onset and success

Author: Day, FR, Helgason, H, Chasman, DI, Rose, LM, Loh, P-R, Scott, RA, Helgason, A, Kong, A, Masson, G, Magnusson, OT, Gudbjartsson, D, Thorsteinsdottir, U, Buring, JE, Ridker, PM, Sulem, P, Stefansson, K, Ong, KK, Perry, JRB, Day, Felix [0000-0003-3789-7651], Ong, Kenneth [0000-0003-4689-7530], Perry, John [0000-0001-6483-3771], and Apollo - University of Cambridge Repository
Subjects: Adult, Male, Behavior, Adolescent, Sexual Behavior, Puberty, Age Factors, Coitus, Estrogen Receptor alpha, Membrane Proteins, RNA-Binding Proteins, Nerve Tissue Proteins, Young Adult, Methionine Sulfoxide Reductases, Humans, Female, Cell Adhesion Molecules, Genome-Wide Association Study
Abstract: The ages of puberty, first sexual intercourse and first birth signify the onset of reproductive ability, behavior and success, respectively. In a genome-wide association study of 125,667 UK Biobank participants, we identify 38 loci associated (P < 5 × 10(-8)) with age at first sexual intercourse. These findings were taken forward in 241,910 men and women from Iceland and 20,187 women from the Women's Genome Health Study. Several of the identified loci also exhibit associations (P < 5 × 10(-8)) with other reproductive and behavioral traits, including age at first birth (variants in or near ESR1 and RBM6-SEMA3F), number of children (CADM2 and ESR1), irritable temperament (MSRA) and risk-taking propensity (CADM2). Mendelian randomization analyses infer causal influences of earlier puberty timing on earlier first sexual intercourse, earlier first birth and lower educational attainment. In turn, likely causal consequences of earlier first sexual intercourse include reproductive, educational, psychiatric and cardiometabolic outcomes.
Published: 2016

14. Quality control and conduct of genome-wide association meta-analyses

Author: WINKLER TW, DAY FR, CROTEAU CHONKA DC, WOOD AR, LOCKE AE, MAGI R, FERREIRA T, FALL T, GRAFF M, JUSTICE AE, LUAN J, GUSTAFSSON S, RANDAL JC, VEDANTAM S, WORKALEMAHU T, KILPELAINEN TO, SCHERAG A, ESKO T, KUTALIK Z, HEID IM, LOOS RJ, Genetic Investigation of Anthropometric Traits GIANT Consortium, MANUNTA , PAOLO, Winkler, Tw, Day, Fr, CROTEAU CHONKA, Dc, Wood, Ar, Locke, Ae, Magi, R, Ferreira, T, Fall, T, Graff, M, Justice, Ae, Luan, J, Gustafsson, S, Randal, Jc, Vedantam, S, Workalemahu, T, Kilpelainen, To, Scherag, A, Esko, T, Kutalik, Z, Heid, Im, Loos, Rj, Genetic Investigation of Anthropometric Traits GIANT, Consortium, and Manunta, Paolo
Published: 2014

15. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

Author: Day, FR, Ruth, KS, Thompson, DJ, Lunetta, KL, Pervjakova, N, Chasman, DI, Stolk, L, Finucane, HK, Sulem, P, Bulik-Sullivan, B, Esko, T, Johnson, AD, Elks, CE, Franceschini, N, He, C, Altmaier, E, Brody, JA, Franke, LL, EHuffman, J, Keller, MF, McArdle, PF, Nutile, T, Porcu, E, Robino, A, Rose, LM, Schick, UM, Smith, JA, Teumer, A, Traglia, M, Vuckovic, D, Yao, J, Zhao, W, Albrecht, E, Amin, N, Corre, T, Hottenga, JJ, Mangino, M, Smith, AV, Tanaka, T, Abecasis, GR, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Arndt, V, Arnold, AM, Barbieri, C, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bernstein, L, Bielinski, SJ, Blomqvist, C, Boerwinkle, E, Bogdanova, NV, Bojesen, SE, Bolla, MK, Borresen-Dale, AL, Boutin, TS, Brauch, H, Brenner, H, Brüning, T, Burwinkel, B, Campbell, A, Campbell, H, Chanock, SJ, Chapman, JR, Chen, YDI, Chenevix-Trench, G, and Couch, FJ
Abstract: © 2015 Nature America, Inc. Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in -1/470,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (-1/46% increase in risk per year; P = 3 × 10 -14), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
Published: 2015
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16. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D, Winkler, TW, Croteau-Chonka, DC, Ferreira, T, Locke, AE, Mägi, R, Strawbridge, RJ, Pers, TH, Fischer, K, Justice, AE, Workalemahu, T, Wu, JMW, Buchkovich, ML, Heard-Costa, NL, Roman, TS, Drong, AW, Song, C, Gustafsson, S, Day, FR, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, JC, Scherag, A, Vedantam, S, Wood, AR, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, CT, Schmidt, EM, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg-Gresham, JL, Buyske, S, Demirkan, A, Ehret, GB, Feitosa, MF, Goel, A, Jackson, AU, Johnson, T, Kleber, ME, Kristiansson, K, Mangino, M, Leach, IM, Medina-Gomez, C, Palmer, CD, Pasko, D, Pechlivanis, S, Peters, MJ, Prokopenko, I, Stančáková, A, Sung, YJ, Tanaka, T, Teumer, A, Van Vliet-Ostaptchouk, JV, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, GM, Bandinelli, S, Barrett, A, Bellis, C, Bennett, AJ, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, DB, Caspersen, IH, Clarke, R, Daw, EW, Deelen, J, Deelman, E, Delgado, G, Doney, AS, Eklund, N, Erdos, MR, Estrada, K, Eury, E, Friedrich, N, Garcia, ME, Giedraitis, V, Gigante, B, Go, AS, Golay, A, Grallert, H, Grammer, TB, Gräßler, J, Grewal, J, Groves, CJ, Haller, T, and Hallmans, G
Subjects: Male, ReproGen Consortium, Transcription, Genetic, Cardiovascular, Epigenesis, Genetic, Body Mass Index, PAGE Consortium, Models, Adipocytes, 2.1 Biological and endogenous factors, Insulin, Body Fat Distribution, Aetiology, Sex Characteristics, Genome, Adipogenesis, Continental Population Groups, Diabetes, Age Factors, CARDIOGRAMplusC4D Consortium, Single Nucleotide, Stroke, Europe, Adipose Tissue, GEFOS Consortium, Female, ADIPOGen Consortium, Transcription, Human, General Science & Technology, ICBP, Quantitative Trait Loci, Neovascularization, Physiologic, Polymorphism, Single Nucleotide, Models, Biological, GENIE Consortium, MAGIC Investigators, Genetic, Genetics, Humans, Obesity, Polymorphism, Physiologic, Metabolic and endocrine, Neovascularization, Nutrition, Genome, Human, Waist-Hip Ratio, CKDGen Consortium, Racial Groups, Human Genome, Biological, MuTHER Consortium, GLGC, International Endogene Consortium, Insulin Resistance, LifeLines Cohort Study, Epigenesis, Genome-Wide Association Study
Abstract: © 2015, Macmillan Publishers Limited. All rights reserved. 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, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P
Published: 2015

17. Large-Scale Genomic Analyses Link Reproductive Aging to Hypothalamic Signaling, Breast Cancer Susceptibility, and BRCA1-Mediated DNA Repair EDITORIAL COMMENT

Author: Day, FR, Ruth, KS, Thompson, DJ, Lunetta, KL, Pervjakova, N, Chasman, DI, Stolk, Lisette, Finucane, HK, Sulem, P, Bulik-Sullivan, B, Esko, T, Johnson, AD, Elks, CE, Franceschini, N, He, C, Altmaier, E, Brody, JA, Franke, LL, Huffman, JE, Keller, MF, McArdle, PF, Nutile, T, Porcu, E, Robino, A, Rose, LM, Schick, UM, Smith, JA, Teumer, A, Traglia, M, Vuckovic, D, Yao, J, Zhao, W, Albrecht, E, Amin, Najaf, Corre, T, Hottenga, JJ (Jouke Jan), Mangino, M, Smith, AV, Tanaka, T, Abecasis, GR, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Arndt, V, Arnold, AM, Barbieri, C, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bernstein, L, Bielinski, SJ, Blomqvist, C, Boerwinkle, E, Bogdanova, NV, Bojesen, SE, Bolla, MK, Borresen-Dale, AL, Boutin, TS, Brauch, H, Brenner, H, Bruning, T, Burwinkel, B, Campbell, A (Archie), Campbell, H, Chanock, SJ, Chapman, JR, Chen, YDI, Chenevix-Trench, G, Couch, FJ, Coviello, AD, Cox, A, Czene, K, Darabi, H, de Vivo, I, Demerath, EW, Dennis, J, Devilee, P, Dork, T, dos-Santos-Silva, I, Dunning, AM, Eicher, JD, Fasching, PA, Faul, JD, Figueroa, J, Flesch-Janys, D, Gandin, I, Garcia, ME, Garcia-Closas, M, Giles, GG, Girotto, GG, Goldberg, MS, Gonzalez-Neira, A, Goodarzi, MO, Grove, ML, Gudbjartsson, DF, Guenel, P, Guo, XQ, Haiman, CA, Hall, P, Hamann, U, Henderson, BE, Hocking, LJ, Hofman, Bert, Homuth, G, Hooning, Maartje, Hopper, JL, Hu, FB, Huang, JY, Humphreys, K, Hunter, DJ, Jakubowska, A, Jones, SE, Kabisch, M, Karasik, D, Knight, JA, Kolcic, I, Kooperberg, C, Kosma, VM, Kriebel, J, Kristensen, V, Lambrechts, D, Langenberg, C, Li, JM, Li, X, Lindstrom, S, Liu, YM, Luan, JA, Lubinski, J, Magi, R, Mannermaa, A, Manz, J, Margolin, S, Marten, J, Martin, NG, Masciullo, C, Meindl, A, Michailidou, K, Mihailov, E, Milani, L, Milne, RL, Muller-Nurasyid, M, Nalls, M, Neale, BM, Nevanlinna, H, Neven, P, Newman, AB, Nordestgaard, BG, Olson, JE, Padmanabhan, S, Peterlongo, P, Peters, U, Petersmann, A, Peto, J, Pharoah, PDP, Pirastu, NN, Pirie, A, Pistis, G, Polasek, O, Porteous, D, Psaty, BM, Pylkas, K, Radice, P, Raffel, LJ, Rivadeneira, Fernando, Rudan, I, Rudolph, A, Ruggiero, D, Sala, CF, Sanna, S, Sawyer, EJ, Schlessinger, D, Schmidt, MK (Marjanka), Schmidt, F, Schmutzler, RK, Schoemaker, MJ, Scott, RA, Seynaeve, Caroline, Simard, J, Sorice, R, Southey, MC, Stockl, D, Strauch, K, Swerdlow, A, Taylor, KD, Thorsteinsdottir, U, Toland, AE, Tomlinson, I, Truong, T, Tryggvadottir, L, Turner, ST, Vozzi, D, Wang, Q (Qing), Wellons, M, Willemsen, G, Wilson, JF, Winqvist, R, Wolffenbuttel, BBHR, Wright, AF, Yannoukakos, D, Zemunik, T, Zheng, W, Zygmunt, M, Bergmann, S, Boomsma, DI, Buring, JE, Ferrucci, L, Montgomery, GW, Gudnason, V, Spector, TD, Duijn, Cornelia, Alizadeh, BZ, Ciullo, M, Crisponi, L, Easton, DF, Gasparini, PP, Gieger, C, Harris, TB, Hayward, C, Kardia, SLR, Kraft, P, McKnight, B, Metspalu, A, Morrison, AC, Reiner, AP, Ridker, PM, Rotter, JI, Toniolo, D, Uitterlinden, André, Ulivi, S, Volzke, H, Wareham, NJ, Weir, DR, Yerges-Armstrong, LM, Price, AL, Stefansson, K, Visser, Jenny, Ong, KK, Chang-Claude, J, Murabito, JM, Perry, JRB, Murray, A, Systems Ecology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Internal Medicine, Epidemiology, Medical Oncology, and Clinical Genetics
Subjects: SDG 3 - Good Health and Well-being
Published: 2015
Full Text: View/download PDF

18. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author: Kilpelainen, TO, Carli, J F M, Skowronski, A A, Sun, Q, Kriebel, J, Feitosa, MF, Hedman, AK, Drong, AW, Hayes, J E, Zhao, JH, Pers, TH, Schick, U, Grarup, N, Kutalik, Z, Trompet, S, Mangino, M, Kristiansson, K, Beekman, M, Lyytikainen, LP, Eriksson, J, Henneman, Peter, Lahti, J, Tanaka, T, Luan, JA, Del Greco, F, Pasko, D, Renstrom, F, Willems, SM, Mahajan, A, Rose, LM, Guo, XQ, Liu, YM, Kleber, ME, Perusse, L, Gaunt, T, Ahluwalia, TS, Sung, YJ, Ramos, YF, Amin, Najaf, Amuzu, A, Barroso, I, Bellis, C, Blangero, J, Buckley, BM, Bohringer, S, Chen, YDI, de Craen, A J N, Crosslin, DR, Dale, CE, Dastani, Z, Day, FR, Deelen, J, Delgado, GE, Demirkan, Ayse, Finucane, FM, Ford, I, Garcia, ME, Gieger, C, Gustafsson, S, Hallmans, G, Hankinson, SE, Havulinna, AS, Herder, Cindy, Hernandez, D, Hicks, AA, Hunter, DJ, Illig, T, Ingelsson, E, Ioan-Facsinay, A, Jansson, JO, Jenny, NS, Jorgensen, ME, Jorgensen, T, Karlsson, M, Koenig, W, Kraft, P, Kwekkeboom, J, Laatikainen, T, Ladwig, KH, LeDuc, C A, Lowe, G, Lu, YC, Marques-Vidal, P, Meisinger, C, Menni, C, Morris, AP, Myers, RH, Mannisto, S, Nalls, MA, Paternoster, L, Peters, A, Pradhan, A D, Rankinen, T, Rasmussen-Torvik, LJ, Rathmann, W, Rice, TK, Richards, JB, Ridker, PM, Sattar, N, Savage, DB, Soderberg, S, Timpson, NJ, Vandenput, L, van Heemst, D, Uh, HW, Vohl, MC, Walker, M, Wichmann, HE, Widen, E, Wood, AR, Yao, J, Zeller, T, Zhang, YY, Meulenbelt, I, Kloppenburg, M, Astrup, A, Sorensen, TIA, Sarzynski, MA, Rao, DC, Jousilahti, P, Vartiainen, E, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Kajantie, E, Osmond, C, Palotie, A, Eriksson, JG, Heliovaara, M, Knekt, PB, Koskinen, S, Jula, A, Perola, M, Huupponen, R K, Viikari, JS, Kahonen, M, Lehtimaki, T, Raitakari, OT, Mellstrom, D, Lorentzon, M, Casas, JP, Bandinelli, S, Marz, W, Isaacs, Aaron, van Dijk, KW, Duijn, Cornelia, Harris, TB, Bouchard, C, Allison, MA, Chasman, DI, Ohlsson, C, Lind, L, Scott, RA, Langenberg, C, Wareham, NJ, Ferrucci, L, Frayling, TM, Pramstaller, PP, Borecki, IB, Waterworth, DM, Bergmann, S, Waeber, G, Vollenweider, P, Vestergaard, H, Hansen, T, Pedersen, O, Hu, FB, Slagboom, PE (Eline), Grallert, H, Spector, TD, Jukema, JW, Klein, RJ, Schadt, EE, Franks, PW, Lindgren, CM, Leibel, R L, Loos, RJF, Kilpelainen, TO, Carli, J F M, Skowronski, A A, Sun, Q, Kriebel, J, Feitosa, MF, Hedman, AK, Drong, AW, Hayes, J E, Zhao, JH, Pers, TH, Schick, U, Grarup, N, Kutalik, Z, Trompet, S, Mangino, M, Kristiansson, K, Beekman, M, Lyytikainen, LP, Eriksson, J, Henneman, Peter, Lahti, J, Tanaka, T, Luan, JA, Del Greco, F, Pasko, D, Renstrom, F, Willems, SM, Mahajan, A, Rose, LM, Guo, XQ, Liu, YM, Kleber, ME, Perusse, L, Gaunt, T, Ahluwalia, TS, Sung, YJ, Ramos, YF, Amin, Najaf, Amuzu, A, Barroso, I, Bellis, C, Blangero, J, Buckley, BM, Bohringer, S, Chen, YDI, de Craen, A J N, Crosslin, DR, Dale, CE, Dastani, Z, Day, FR, Deelen, J, Delgado, GE, Demirkan, Ayse, Finucane, FM, Ford, I, Garcia, ME, Gieger, C, Gustafsson, S, Hallmans, G, Hankinson, SE, Havulinna, AS, Herder, Cindy, Hernandez, D, Hicks, AA, Hunter, DJ, Illig, T, Ingelsson, E, Ioan-Facsinay, A, Jansson, JO, Jenny, NS, Jorgensen, ME, Jorgensen, T, Karlsson, M, Koenig, W, Kraft, P, Kwekkeboom, J, Laatikainen, T, Ladwig, KH, LeDuc, C A, Lowe, G, Lu, YC, Marques-Vidal, P, Meisinger, C, Menni, C, Morris, AP, Myers, RH, Mannisto, S, Nalls, MA, Paternoster, L, Peters, A, Pradhan, A D, Rankinen, T, Rasmussen-Torvik, LJ, Rathmann, W, Rice, TK, Richards, JB, Ridker, PM, Sattar, N, Savage, DB, Soderberg, S, Timpson, NJ, Vandenput, L, van Heemst, D, Uh, HW, Vohl, MC, Walker, M, Wichmann, HE, Widen, E, Wood, AR, Yao, J, Zeller, T, Zhang, YY, Meulenbelt, I, Kloppenburg, M, Astrup, A, Sorensen, TIA, Sarzynski, MA, Rao, DC, Jousilahti, P, Vartiainen, E, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Kajantie, E, Osmond, C, Palotie, A, Eriksson, JG, Heliovaara, M, Knekt, PB, Koskinen, S, Jula, A, Perola, M, Huupponen, R K, Viikari, JS, Kahonen, M, Lehtimaki, T, Raitakari, OT, Mellstrom, D, Lorentzon, M, Casas, JP, Bandinelli, S, Marz, W, Isaacs, Aaron, van Dijk, KW, Duijn, Cornelia, Harris, TB, Bouchard, C, Allison, MA, Chasman, DI, Ohlsson, C, Lind, L, Scott, RA, Langenberg, C, Wareham, NJ, Ferrucci, L, Frayling, TM, Pramstaller, PP, Borecki, IB, Waterworth, DM, Bergmann, S, Waeber, G, Vollenweider, P, Vestergaard, H, Hansen, T, Pedersen, O, Hu, FB, Slagboom, PE (Eline), Grallert, H, Spector, TD, Jukema, JW, Klein, RJ, Schadt, EE, Franks, PW, Lindgren, CM, Leibel, R L, and Loos, RJF
Published: 2016

19. y New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author: Lu, YC, Day, FR, Gustafsson, S, Buchkovich, ML, Na, JB, Bataille, V, Cousminer, DL, Dastani, Z, Drong, AW, Esko, T, Evans, DM, Falchi, M, Feitosa, MF, Ferreira, T, Hedman, AK, Haring, R, Hysi, PG, Iles, MM, Justice, AE, Kanoni, S, Lagou, V, Li, R, Li, X, Locke, A, Lu, C, Magi, R, Perry, JRB, Pers, TH, Qi, QB, Sanna, M, Schmidt, EM, Scott, WR, Shungin, D, Teumer, A, Vinkhuyzen, AAE, Walker, RW, Westra, HJ, Zhang, MF, Zhang, WH, Zhao, JH, Zhu, ZH, Afzal, U, Ahluwalia, TS, Bakker, SJL, Bellis, C, Bonnefond, A, Borodulin, K, Buchman, AS, Cederholm, T, Choh, AC, Choi, HJ, Curran, JE, de Groot, LCPGM (Lisette), De Jager, PL, Dhonukshe-Rutten, RAM, Enneman, Anke, Eury, E, Evans, DS, Forsen, T, Friedrich, N, Fumeron, F, Garcia, ME, Gartner, S, Han, BG, Havulinna, AS, Hayward, C, Hernandez, D, Hillege, H, Ittermann, T, Kent, JW, Kolcic, I, Laatikainen, T, Lahti, J, Leach, IM, Lee, CG, Lee, JY, Liu, T, Liu, YF, Lobbens, S, Loh, M, Lyytikainen, LP, Medina-Gomez, C, Michaelsson, K, Nalls, MA, Nielson, CM, Oozageer, L, Pascoe, L, Paternoster, L, Polasek, O, Ripatti, S, Sarzynski, MA, Shin, CS, Narancic, NS, Spira, D, Srikanth, P, Steinhagen-Thiessen, E, Sung, YJ, Swart, KMA, Taittonen, L, Tanaka, T, Tikkanen, E, van der Velde, Nathalie, Schoor, NM, Verweij, N (Niek), Wright, AF, Yu, L, Zmuda, JM, Eklund, N, Forrester, T, Grarup, N, Jackson, AU, Kristiansson, K, Kuulasmaa, T, Kuusisto, J, Lichtner, P, Luan, JA, Mahajan, A, Mannisto, S, Palmer, CD, Ried, JS, Scott, RA, Stancakova, A, Wagner, PJ, Demirkan, Ayse, Doring, A, Gudnason, V, Kiel, DP, Kuhnel, B, Mangino, M, McKnight, B, Menni, C, O'Connell, JR, Oostra, Ben, Shuldiner, AR, Song, KJ, Vandenput, L, Duijn, Cornelia, Vollenweider, P, White, CC, Boehnke, M, Boettcher, Y, Cooper, RS, Forouhi, NG, Gieger, C, Grallert, H, Hingorani, A, Jorgensen, T, Jousilahti, P, Kivimaki, M, Kumari, M, Laakso, M, Langenberg, C, Linneberg, A, Luke, A, McKenzie, CA, Palotie, A, Pedersen, O, Peters, A, Strauch, K, Tayo, BO, Wareham, NJ, Bennett, DA, Bertram, L, Blangero, J, Bluher, M, Bouchard, C, Campbell, H, Cho, NH, Cummings, SR, Czerwinski, SA, Demuth, I, Eckardt, R, Eriksson, JG, Ferrucci, L, Franco Duran, OH, Froguel, P, Gansevoort, RT, Hansen, T, Harris, TB, Hastie, N, Heliovaara, M, Hofman, Bert, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Knekt, PB, Koskinen, S, Kovacs, P, Lehtimaki, T, Lind, L, Liu, YM, Orwoll, ES, Osmond, C, Perola, M, Perusse, L, Raitakari, OT, Rankinen, T, Rao, DC, Rice, TK, Rivadeneira, Fernando, Rudan, I, Salomaa, V, Sorensen, TIA, Stumvoll, M, Tonjes, A, Towne, B, Tranah, GJ, Tremblay, A, Uitterlinden, André, van der Harst, P, Vartiainen, E, Viikari, JS, Vitart, V, Vohl, MC, Volzke, H, Walker, M, Wallaschofski, H, Wild, S, Wilson, JF, Yengo, L, Bishop, DT, Borecki, IB, Chambers, JC, Cupples, LA, Dehghan, Abbas, Deloukas, P, Fatemifar, G, Fox, C, Furey, TS, Franke, L, Han, JL, Hunter, DJ, Karjalainen, J, Karpe, F, Kaplan, RC, Kooner, JS, McCarthy, MI, Murabito, JM, Morris, AP, Bishop, JAN, North, KE, Ohlsson, C, Ong, KK, Prokopenko, I, Richards, JB, Schadt, EE, Spector, TD, Widen, E, Willer, CJ, Yang, Jiaqi, Ingelsson, E, Mohlke, KL, Hirschhorn, JN, Pospisilik, JA, Zillikens, M.C., Lindgren, C, Kilpelainen, TO, Loos, RJF, Lu, YC, Day, FR, Gustafsson, S, Buchkovich, ML, Na, JB, Bataille, V, Cousminer, DL, Dastani, Z, Drong, AW, Esko, T, Evans, DM, Falchi, M, Feitosa, MF, Ferreira, T, Hedman, AK, Haring, R, Hysi, PG, Iles, MM, Justice, AE, Kanoni, S, Lagou, V, Li, R, Li, X, Locke, A, Lu, C, Magi, R, Perry, JRB, Pers, TH, Qi, QB, Sanna, M, Schmidt, EM, Scott, WR, Shungin, D, Teumer, A, Vinkhuyzen, AAE, Walker, RW, Westra, HJ, Zhang, MF, Zhang, WH, Zhao, JH, Zhu, ZH, Afzal, U, Ahluwalia, TS, Bakker, SJL, Bellis, C, Bonnefond, A, Borodulin, K, Buchman, AS, Cederholm, T, Choh, AC, Choi, HJ, Curran, JE, de Groot, LCPGM (Lisette), De Jager, PL, Dhonukshe-Rutten, RAM, Enneman, Anke, Eury, E, Evans, DS, Forsen, T, Friedrich, N, Fumeron, F, Garcia, ME, Gartner, S, Han, BG, Havulinna, AS, Hayward, C, Hernandez, D, Hillege, H, Ittermann, T, Kent, JW, Kolcic, I, Laatikainen, T, Lahti, J, Leach, IM, Lee, CG, Lee, JY, Liu, T, Liu, YF, Lobbens, S, Loh, M, Lyytikainen, LP, Medina-Gomez, C, Michaelsson, K, Nalls, MA, Nielson, CM, Oozageer, L, Pascoe, L, Paternoster, L, Polasek, O, Ripatti, S, Sarzynski, MA, Shin, CS, Narancic, NS, Spira, D, Srikanth, P, Steinhagen-Thiessen, E, Sung, YJ, Swart, KMA, Taittonen, L, Tanaka, T, Tikkanen, E, van der Velde, Nathalie, Schoor, NM, Verweij, N (Niek), Wright, AF, Yu, L, Zmuda, JM, Eklund, N, Forrester, T, Grarup, N, Jackson, AU, Kristiansson, K, Kuulasmaa, T, Kuusisto, J, Lichtner, P, Luan, JA, Mahajan, A, Mannisto, S, Palmer, CD, Ried, JS, Scott, RA, Stancakova, A, Wagner, PJ, Demirkan, Ayse, Doring, A, Gudnason, V, Kiel, DP, Kuhnel, B, Mangino, M, McKnight, B, Menni, C, O'Connell, JR, Oostra, Ben, Shuldiner, AR, Song, KJ, Vandenput, L, Duijn, Cornelia, Vollenweider, P, White, CC, Boehnke, M, Boettcher, Y, Cooper, RS, Forouhi, NG, Gieger, C, Grallert, H, Hingorani, A, Jorgensen, T, Jousilahti, P, Kivimaki, M, Kumari, M, Laakso, M, Langenberg, C, Linneberg, A, Luke, A, McKenzie, CA, Palotie, A, Pedersen, O, Peters, A, Strauch, K, Tayo, BO, Wareham, NJ, Bennett, DA, Bertram, L, Blangero, J, Bluher, M, Bouchard, C, Campbell, H, Cho, NH, Cummings, SR, Czerwinski, SA, Demuth, I, Eckardt, R, Eriksson, JG, Ferrucci, L, Franco Duran, OH, Froguel, P, Gansevoort, RT, Hansen, T, Harris, TB, Hastie, N, Heliovaara, M, Hofman, Bert, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Knekt, PB, Koskinen, S, Kovacs, P, Lehtimaki, T, Lind, L, Liu, YM, Orwoll, ES, Osmond, C, Perola, M, Perusse, L, Raitakari, OT, Rankinen, T, Rao, DC, Rice, TK, Rivadeneira, Fernando, Rudan, I, Salomaa, V, Sorensen, TIA, Stumvoll, M, Tonjes, A, Towne, B, Tranah, GJ, Tremblay, A, Uitterlinden, André, van der Harst, P, Vartiainen, E, Viikari, JS, Vitart, V, Vohl, MC, Volzke, H, Walker, M, Wallaschofski, H, Wild, S, Wilson, JF, Yengo, L, Bishop, DT, Borecki, IB, Chambers, JC, Cupples, LA, Dehghan, Abbas, Deloukas, P, Fatemifar, G, Fox, C, Furey, TS, Franke, L, Han, JL, Hunter, DJ, Karjalainen, J, Karpe, F, Kaplan, RC, Kooner, JS, McCarthy, MI, Murabito, JM, Morris, AP, Bishop, JAN, North, KE, Ohlsson, C, Ong, KK, Prokopenko, I, Richards, JB, Schadt, EE, Spector, TD, Widen, E, Willer, CJ, Yang, Jiaqi, Ingelsson, E, Mohlke, KL, Hirschhorn, JN, Pospisilik, JA, Zillikens, M.C., Lindgren, C, Kilpelainen, TO, and Loos, RJF
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P < 5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Published: 2016

20. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Author: Berndt SI, Gustafsson S, Mxe4gi R, Ganna A, Wheeler E, Feitosa MF, Justice AE, Monda KL, Croteau-Chonka DC, Day FR, Esko T, Fall T, Ferreira T, Gentilini D, Jackson AU, Hottenga JJ, Willemsen G, Boomsma DI, Penninx B, Strachan DP, Thorsteinsdottir U, van Duijn CM, Visscher PM, Di Blasio AM, Hirschhorn JN, Lindgren CM, Morris AP, Meyre D, Scherag A, McCarthy MI, Speliotes EK, North KE, Loos RJ, and Ingelsson E
Published: 2013

21. Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

Author: Randall, JC, Winkler, TW, Kutalik, Z, Berndt, SI, Jackson, AU, Monda, KL, Kilpeläinen, TO, Esko, T, Mägi, R, Li, S, Workalemahu, T, Feitosa, MF, Croteau-Chonka, DC, Day, FR, Fall, T, Ferreira, T, Gustafsson, S, Locke, AE, Mathieson, I, Scherag, A, Vedantam, S, Wood, AR, Liang, L, Steinthorsdottir, V, Thorleifsson, G, Dermitzakis, ET, Dimas, AS, Karpe, F, Min, JL, Nicholson, G, Clegg, DJ, Person, T, Krohn, JP, Bauer, S, Buechler, C, Eisinger, K, DIAGRAM Consortium, Bonnefond, A, Froguel, P, MAGIC Investigators, Hottenga, JJ, Prokopenko, I, Waite, LL, Harris, TB, Smith, AV, Shuldiner, AR, McArdle, WL, Caulfield, MJ, Munroe, PB, Grönberg, H, Chen, YD, Li, G, Beckmann, JS, Johnson, T, Thorsteinsdottir, U, Teder-Laving, M, Khaw, KT, Wareham, NJ, Zhao, JH, Amin, N, Oostra, BA, Kraja, AT, Province, MA, Cupples, LA, Heard-Costa, NL, Kaprio, J, Ripatti, S, Surakka, I, Collins, FS, Saramies, J, Tuomilehto, J, Jula, A, Salomaa, V, Erdmann, J, Hengstenberg, C, Loley, C, Schunkert, H, Lamina, C, Wichmann, HE, Albrecht, E, Gieger, C, Hicks, AA, Johansson, A, Pramstaller, PP, Kathiresan, S, Speliotes, EK, Penninx, B, Hartikainen, AL, Jarvelin, MR, Gyllensten, U, Boomsma, DI, Campbell, H, Wilson, JF, Chanock, SJ, Farrall, M, Goel, A, Medina-Gomez, C, Rivadeneira, F, Estrada, K, Uitterlinden, AG, Hofman, A, Zillikens, MC, den Heijer, M, Kiemeney, LA, Maschio, A, Hall, P, Tyrer, J, Teumer, A, Völzke, H, Kovacs, P, Tönjes, A, Mangino, M, Spector, TD, Hayward, C, Rudan, I, Hall, AS, Samani, NJ, Attwood, AP, Sambrook, JG, Hung, J, Palmer, LJ, Lokki, ML, Sinisalo, J, Boucher, G, Huikuri, H, Lorentzon, M, Ohlsson, C, Eklund, N, Eriksson, JG, Barlassina, C, Rivolta, C, Nolte, IM, Snieder, H, Van der Klauw, MM, Van Vliet-Ostaptchouk, JV, Gejman, PV, Shi, J, Jacobs, KB, Wang, Z, Bakker, SJ, Mateo Leach, I, Navis, G, van der Harst, P, Martin, NG, Medland, SE, Montgomery, GW, Yang, J, Chasman, DI, Ridker, PM, Rose, LM, Lehtimäki, T, Raitakari, O, Absher, D, Iribarren, C, Basart, H, Hovingh, KG, Hyppönen, E, Power, C, Anderson, D, Beilby, JP, Hui, J, Jolley, J, Sager, H, Bornstein, SR, Schwarz, PE, Kristiansson, K, Perola, M, Lindström, J, Swift, AJ, Uusitupa, M, Atalay, M, Lakka, TA, Rauramaa, R, Bolton, JL, Fowkes, G, Fraser, RM, Price, JF, Fischer, K, Krjutå Kov, K, Metspalu, A, Mihailov, E, Langenberg, C, Luan, J, Ong, KK, Chines, PS, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Edkins, S, Franks, PW, Hallmans, G, Shungin, D, Morris, AD, Palmer, CN, Erbel, R, Moebus, S, Nöthen, MM, Pechlivanis, S, Hveem, K, Narisu, N, Hamsten, A, Humphries, SE, Strawbridge, RJ, Tremoli, E, Grallert, H, Thorand, B, Illig, T, Koenig, W, Müller-Nurasyid, M, Peters, A, Boehm, BO, Kleber, ME, März, W, Winkelmann, BR, Kuusisto, J, Laakso, M, Arveiler, D, Cesana, G, Kuulasmaa, K, Virtamo, J, Yarnell, JW, Kuh, D, Wong, A, Lind, L, de Faire, U, Gigante, B, Magnusson, PK, Pedersen, NL, Dedoussis, G, Dimitriou, M, Kolovou, G, Kanoni, S, Stirrups, K, Bonnycastle, LL, Njølstad, I, Wilsgaard, T, Ganna, A, Rehnberg, E, Hingorani, A, Kivimaki, M, Kumari, M, Assimes, TL, Barroso, I, Boehnke, M, Borecki, IB, Deloukas, P, Fox, CS, Frayling, T, Groop, LC, Haritunians, T, Hunter, D, Ingelsson, E, Kaplan, R, Mohlke, KL, O'Connell, JR, Schlessinger, D, Strachan, DP, Stefansson, K, van Duijn, CM, Abecasis, GR, McCarthy, MI, Hirschhorn, JN, Qi, L, Loos, RJ, Lindgren, CM, North, KE, Heid, IM, Hjelt Institute (-2014), Department of Public Health, Institute for Molecular Medicine Finland, Samuli Olli Ripatti / Principal Investigator, Haartman Institute (-2014), Transplantation Laboratory, Kardiologian yksikkö, Department of Medicine, Clinicum, Department of General Practice and Primary Health Care, Diabetes and Obesity Research Program, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Genetic Epidemiology, DIAGRAM Consortium, MAGIC Investigators, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Epidemiology, Erasmus School of Social and Behavioural Sciences, Clinical Genetics, Internal Medicine, Public Health, Surgery, Medical Research Council (MRC), and Dermitzakis, Emmanouil
Subjects: Male, Medicin och hälsovetenskap, Epidemiology, VARIANTS, Anthropometry/methods, Body Height/genetics, Body Mass Index, Body Weight/genetics, Body Weights and Measures, Female, Genetic Loci, Genome, Human, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Sex Characteristics, Waist Circumference/genetics, Waist-Hip Ratio, Medical and Health Sciences, ddc:576.5, GENETICS & HEREDITY, ADULT HEIGHT, RISK, Anthropometry, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, OBESITY, Genetic Epidemiology, Medicine, PPAR-GAMMA, Waist Circumference, Life Sciences & Biomedicine, Medical Genetics, Research Article, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, lcsh:QH426-470, 515 Psychology, education, DIAGRAM Consortium, Endocrinology and Diabetes, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, MAGIC Investigators, ddc:610, ENZYME-ACTIVITIES, METAANALYSIS, Medicinsk genetik, 0604 Genetics, Science & Technology, Body Weight, FAT DISTRIBUTION, Body Height, BODY-MASS INDEX, lcsh:Genetics, 3121 General medicine, internal medicine and other clinical medicine, 3111 Biomedicine, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Developmental Biology
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, Author Summary Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Published: 2013
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22. Biological interpretation of genome-wide association studies using predicted gene functions

Author: Pers, T, Karjalainen, J, Chan, Y, Westra, H, Wood, A, Yang, J, Lui, J, Vedantam, S, Gustafsson, S, Esko, T, Frayling, T, Speliotes, E, Boehnke, M, Raychaudhuri, S, Fehrmann, R, Hirschhorn, J, Franke, L, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Ferreira, T, Jackson, A, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, 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, E, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Mateo 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, A, 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, 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, I, 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, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, van Duijn, C, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L, 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, 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 E, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, 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, Ärnlöv 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 A, 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, 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 I, Bornstein SR, Bovet P, BRAMBILLA, PAOLO, 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 E, 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, 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, Thorsteinsdottir U, Barroso I, Fox CS, North KE, Strachan DP, Beckmann JS, Berndt SI, Borecki IB, McCarthy MI, Metspalu A, Stefansson K, Uitterlinden AG, van Duijn CM, Willer CJ, Price AL, Lettre G, Loos RJ, Weedon MN, Ingelsson E, O'Connell JR, Abecasis GR, Chasman DI, Goddard ME, Visscher PM, Frayling T.M., Pers, T, Karjalainen, J, Chan, Y, Westra, H, Wood, A, Yang, J, Lui, J, Vedantam, S, Gustafsson, S, Esko, T, Frayling, T, Speliotes, E, Boehnke, M, Raychaudhuri, S, Fehrmann, R, Hirschhorn, J, Franke, L, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Ferreira, T, Jackson, A, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, 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, E, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Mateo 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, A, 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, 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, I, 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, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, van Duijn, C, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L, 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, 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 E, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, 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, Ärnlöv 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 A, 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, 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 I, Bornstein SR, Bovet P, BRAMBILLA, PAOLO, 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 E, 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, 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, Thorsteinsdottir U, Barroso I, Fox CS, North KE, Strachan DP, Beckmann JS, Berndt SI, Borecki IB, McCarthy MI, Metspalu A, Stefansson K, Uitterlinden AG, van Duijn CM, Willer CJ, Price AL, Lettre G, Loos RJ, Weedon MN, Ingelsson E, O'Connell JR, Abecasis GR, Chasman DI, Goddard ME, Visscher PM, and Frayling T.M.
Abstract: The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.
Published: 2015

23. Rare coding variants and X-linked loci associated with age at menarche

Author: Lunetta, KL, Day, FR, Sulem, P, Ruth, KS, Tung, JY, Hinds, DA, Esko, T, Elks, CE, Altmaier, E, He, CY, Huffman, JE, Mihailov, E, Porcu, E, Robino, A, Rose, LM, Schick, UM, Stolk, Lisette, Teumer, A, Thompson, DJ, Traglia, M, Wang, CA, Yerges-Armstrong, LM, Antoniou, AC, Barbieri, C, Coviello, AD, Cucca, F, Demerath, EW, Dunning, AM, Gandin, I, Grove, ML, Gudbjartsson, DF, Hocking, LJ, Hofman, Bert, Huang, JY, Jackson, RD, Karasik, D, Kriebel, J, Lange, Edmee, Lange, LA, Langenberg, C, Li, X, Luan, JA, Magi, R, Morrison, AC, Padmanabhan, S, Pirie, A, Polasek, O, Porteous, D, Reiner, AP, Rivadeneira, Fernando, Rudan, I, Sala, CF, Schlessinger, D, Scott, RA, Stockl, D, Visser, Jenny, Volker, U, Vozzi, D, Wilson, JG, Zygmunt, M, Boerwinkle, E, Buring, JE, Crisponi, L, Easton, DF, Hayward, C, Hu, FB, Liu, SM (Simin), Metspalu, A, Pennell, CE, Ridker, PM, Strauch, K, Streeten, EA, Toniolo, D, Uitterlinden, André, Ulivi, S, Volzke, H, Wareham, NJ, Wellons, M, Franceschini, N, Chasman, DI, Thorsteinsdottir, U, Murray, A, Stefansson, K, Murabito, JM, Ong, KK, Perry, JRB, Forouhi, NG, Kerrison, ND, Sharp, SJ, Sims, M, Barroso, I, Deloukas, P, McCarthy, MI, Arriola, L, Balkau, B, Barricarte, A, Boeing, H, Franks, PW, Gonzalez, C, Grioni, S, Kaaks, R, Key, TJ, Navarro, C, Nilsson, PM, Overvad, K, Palli, D, Panico, S, Quiros, JR, Rolandsson, O, Sacerdote, C, Sanchez, MJ (Maria-Jose), Slimani, N, Tjonneland, A, Tumino, R, van der A, DL, van der Schouw, YT, Riboli, E, Smith, BH, Campbell, A (Archie), Deary, IJ, McIntosh, AM, Lunetta, KL, Day, FR, Sulem, P, Ruth, KS, Tung, JY, Hinds, DA, Esko, T, Elks, CE, Altmaier, E, He, CY, Huffman, JE, Mihailov, E, Porcu, E, Robino, A, Rose, LM, Schick, UM, Stolk, Lisette, Teumer, A, Thompson, DJ, Traglia, M, Wang, CA, Yerges-Armstrong, LM, Antoniou, AC, Barbieri, C, Coviello, AD, Cucca, F, Demerath, EW, Dunning, AM, Gandin, I, Grove, ML, Gudbjartsson, DF, Hocking, LJ, Hofman, Bert, Huang, JY, Jackson, RD, Karasik, D, Kriebel, J, Lange, Edmee, Lange, LA, Langenberg, C, Li, X, Luan, JA, Magi, R, Morrison, AC, Padmanabhan, S, Pirie, A, Polasek, O, Porteous, D, Reiner, AP, Rivadeneira, Fernando, Rudan, I, Sala, CF, Schlessinger, D, Scott, RA, Stockl, D, Visser, Jenny, Volker, U, Vozzi, D, Wilson, JG, Zygmunt, M, Boerwinkle, E, Buring, JE, Crisponi, L, Easton, DF, Hayward, C, Hu, FB, Liu, SM (Simin), Metspalu, A, Pennell, CE, Ridker, PM, Strauch, K, Streeten, EA, Toniolo, D, Uitterlinden, André, Ulivi, S, Volzke, H, Wareham, NJ, Wellons, M, Franceschini, N, Chasman, DI, Thorsteinsdottir, U, Murray, A, Stefansson, K, Murabito, JM, Ong, KK, Perry, JRB, Forouhi, NG, Kerrison, ND, Sharp, SJ, Sims, M, Barroso, I, Deloukas, P, McCarthy, MI, Arriola, L, Balkau, B, Barricarte, A, Boeing, H, Franks, PW, Gonzalez, C, Grioni, S, Kaaks, R, Key, TJ, Navarro, C, Nilsson, PM, Overvad, K, Palli, D, Panico, S, Quiros, JR, Rolandsson, O, Sacerdote, C, Sanchez, MJ (Maria-Jose), Slimani, N, Tjonneland, A, Tumino, R, van der A, DL, van der Schouw, YT, Riboli, E, Smith, BH, Campbell, A (Archie), Deary, IJ, and McIntosh, AM
Abstract: More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
Published: 2015

24. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Author: Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Berndt, SI, Feitosa, MF, Justice, AE, Monda, KL, Croteau Chonka, DC, Day, FR, Jackson, AU, Randall, JC, Willer, CJ, Winkler, TW, Wood, AR, Hu, YJ, Lee, SH, Lin, DY, Min, JL, Neale, BM, Bragg Gresham, JL, Hottenga, JJ, Huffman, JE, Kleber, ME, König, IR, McArdle, WL, Ngwa, JS, Nolte, IM, Peters, MJ, Rose, LM, Smith, AV, Strawbridge, RJ, Trip, MD, Van Vliet Ostaptchouk, JV, Waite, LL, Zhao, JH, Asselbergs, FW, Attwood, AP, Balmforth, AJ, Bonnycastle, LL, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de, Faire, U, de, Evans, DM, Ferrario, MM, Gejman, PV, Hall, AS, Hartikainen, AL, Heard Costa, NL, Heath, AC, Hu, FB, Hunt, SE, Jacobs, KB, Jansson, JO, Khaw, KT, Kraja, AT, Laitinen, JH, Lakka, TA, Launer, LJ, Lokki, ML, Madden, PA, Magnusson, PK, McKnight, B, Medland, SE, Montgomery, GW, Mühleisen, TW, Munroe, PB, Musk, AW, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CN, Peden, JF, Pramstaller, PP, Saaristo, TE, Sambrook, JG, Sanders, AR, Shin, SY, Stephens, JC, Stolk, RP, Swift, AJ, Theodoraki, EV, Tregouet, DA, Van der Klauw, MM, van Meurs, JB, Vermeulen, SH, Wild, SH, Winkelmann, BR, Witteman, JC, Wolffenbuttel, BH, Wright, AF, Zillikens, MC, Boehm, BO, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, LA, Dedoussis, GV, Eriksson, JG, Franks, PW, Harris, TB, Hicks, AA, Hovingh, KG, Jarvelin, MR, Jöckel, KH, Keinanen Kiukaanniemi, SM, Kiemeney, LA, Levinson, DF, Martin, NG, Morris, AD, Nieminen, MS, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Province, MA, Psaty, BM, Ridker, PM, Samani, NJ, Sørensen, TI, Spector, TD, Uitterlinden, AG, Wareham, NJ, Wichmann, HE, Wilson, JF, Abecasis, GR, Assimes, TL, Borecki, IB, Fox, CS, Groop, LC, Heid, IM, Kaplan, RC, Moffatt, MF, Mohlke, KL, O'Connell, JR, Schadt, EE, Strachan, DP, van, Duijn, CM, Visscher, PM, Di Blasio, AM, Hirschhorn, JN, Lindgren, CM, Morris, AP, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJ, Ingelsson, E., BRAMBILLA, PAOLO, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Berndt, SI, Feitosa, MF, Justice, AE, Monda, KL, Croteau Chonka, DC, Day, FR, Jackson, AU, Randall, JC, Willer, CJ, Winkler, TW, Wood, AR, Hu, YJ, Lee, SH, Lin, DY, Min, JL, Neale, BM, Bragg Gresham, JL, Hottenga, JJ, Huffman, JE, Kleber, ME, König, IR, McArdle, WL, Ngwa, JS, Nolte, IM, Peters, MJ, Rose, LM, Smith, AV, Strawbridge, RJ, Trip, MD, Van Vliet Ostaptchouk, JV, Waite, LL, Zhao, JH, Asselbergs, FW, Attwood, AP, Balmforth, AJ, Bonnycastle, LL, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de, Faire, U, de, Evans, DM, Ferrario, MM, Gejman, PV, Hall, AS, Hartikainen, AL, Heard Costa, NL, Heath, AC, Hu, FB, Hunt, SE, Jacobs, KB, Jansson, JO, Khaw, KT, Kraja, AT, Laitinen, JH, Lakka, TA, Launer, LJ, Lokki, ML, Madden, PA, Magnusson, PK, McKnight, B, Medland, SE, Montgomery, GW, Mühleisen, TW, Munroe, PB, Musk, AW, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CN, Peden, JF, Pramstaller, PP, Saaristo, TE, Sambrook, JG, Sanders, AR, Shin, SY, Stephens, JC, Stolk, RP, Swift, AJ, Theodoraki, EV, Tregouet, DA, Van der Klauw, MM, van Meurs, JB, Vermeulen, SH, Wild, SH, Winkelmann, BR, Witteman, JC, Wolffenbuttel, BH, Wright, AF, Zillikens, MC, Boehm, BO, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, LA, Dedoussis, GV, Eriksson, JG, Franks, PW, Harris, TB, Hicks, AA, Hovingh, KG, Jarvelin, MR, Jöckel, KH, Keinanen Kiukaanniemi, SM, Kiemeney, LA, Levinson, DF, Martin, NG, Morris, AD, Nieminen, MS, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Province, MA, Psaty, BM, Ridker, PM, Samani, NJ, Sørensen, TI, Spector, TD, Uitterlinden, AG, Wareham, NJ, Wichmann, HE, Wilson, JF, Abecasis, GR, Assimes, TL, Borecki, IB, Fox, CS, Groop, LC, Heid, IM, Kaplan, RC, Moffatt, MF, Mohlke, KL, O'Connell, JR, Schadt, EE, Strachan, DP, van, Duijn, CM, Visscher, PM, Di Blasio, AM, Hirschhorn, JN, Lindgren, CM, Morris, AP, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJ, Ingelsson, E., and BRAMBILLA, PAOLO
Abstract: Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups
Published: 2013

25. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

Author: Day, FR, Thompson, DJ, Helgason, H, Chasman, DI, Finucane, H, Sulem, P, Ruth, KS, Whalen, S, Sarkar, AK, Albrecht, E, Altmaier, E, Amini, M, Barbieri, CM, Boutin, T, Campbell, A, Demerath, E, Giri, A, He, C, Hottenga, JJ, Karlsson, R, Kolcic, I, Loh, P-R, Lunetta, KL, Mangino, M, Marco, B, McMahon, G, Medland, SE, Nolte, IM, Noordam, R, Nutile, T, Paternoster, L, Perjakova, N, Porcu, E, Rose, LM, Schraut, KE, Segrè, AV, Smith, AV, Stolk, L, Teumer, A, Andrulis, IL, Bandinelli, S, Beckmann, MW, Benitez, J, Bergmann, S, Bochud, M, Boerwinkle, E, Bojesen, SE, Bolla, MK, Brand, JS, Brauch, H, Brenner, H, Broer, L, Brüning, T, Buring, JE, Campbell, H, Catamo, E, Chanock, S, Chenevix-Trench, G, Corre, T, Couch, FJ, Cousminer, DL, Cox, A, Crisponi, L, Czene, K, Davey Smith, G, De Geus, EJCN, De Mutsert, R, De Vivo, I, Dennis, J, Devilee, P, Dos-Santos-Silva, I, Dunning, AM, Eriksson, JG, Fasching, PA, Fernández-Rhodes, L, Ferrucci, L, Flesch-Janys, D, Franke, L, Gabrielson, M, Gandin, I, Giles, GG, Grallert, H, Gudbjartsson, DF, Guénel, P, Hall, P, Hallberg, E, Hamann, U, Harris, TB, Hartman, CA, Heiss, G, Hooning, MJ, Hopper, JL, Hu, F, Hunter, DJ, Ikram, MA, Im, HK, Järvelin, M-R, Joshi, PK, Karasik, D, Kellis, M, Kutalik, Z, LaChance, G, Lambrechts, D, Langenberg, C, Launer, LJ, Laven, JSE, Lenarduzzi, S, Li, J, Lind, PA, Lindstrom, S, Liu, Y, Luan, J, Mägi, R, Mannermaa, A, Mbarek, H, McCarthy, MI, Meisinger, C, Meitinger, T, Menni, C, Metspalu, A, Michailidou, K, Milani, L, Milne, RL, Montgomery, GW, Mulligan, AM, Nalls, MA, Navarro, P, Nevanlinna, H, Nyholt, DR, Oldehinkel, AJ, O'Mara, TA, Padmanabhan, S, Palotie, A, Pedersen, N, Peters, A, Peto, J, Pharoah, PDP, Pouta, A, Radice, P, Rahman, I, Ring, SM, Robino, A, Rosendaal, FR, Rudan, I, Rueedi, R, Ruggiero, D, Sala, CF, Schmidt, MK, Scott, RA, Shah, M, Sorice, R, Southey, MC, Sovio, U, Stampfer, M, Steri, M, Strauch, K, Tanaka, T, Tikkanen, E, Timpson, NJ, Traglia, M, Truong, T, Tyrer, JP, Uitterlinden, AG, Edwards, DRV, Vitart, V, Völker, U, Vollenweider, P, Wang, Q, Widen, E, Van Dijk, KW, Willemsen, G, Winqvist, R, Wolffenbuttel, BHR, Zhao, JH, Zoledziewska, M, Zygmunt, M, Alizadeh, BZ, Boomsma, DI, Ciullo, M, Cucca, F, Esko, T, Franceschini, N, Gieger, C, Gudnason, V, Hayward, C, Kraft, P, Lawlor, DA, Magnusson, PKE, Martin, NG, Mook-Kanamori, DO, Nohr, EA, Polasek, O, Porteous, D, Price, AL, Ridker, PM, Snieder, H, Spector, TD, Stöckl, D, Toniolo, D, Ulivi, S, Visser, JA, Völzke, H, Wareham, NJ, Wilson, JF, LifeLines Cohort Study, InterAct Consortium, KConFab/AOCS Investigators, Endometrial Cancer Association Consortium, Ovarian Cancer Association Consortium, PRACTICAL Consortium, Spurdle, AB, Thorsteindottir, U, Pollard, KS, Easton, DF, Tung, JY, Chang-Claude, J, Hinds, D, Murray, A, Murabito, JM, Stefansson, K, Ong, KK, and Perry, JRB
Subjects: 2. Zero hunger, genome-wide association studies, cancer, reproductive disorders, 3. Good health
Abstract: The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10$^{−8}$) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.

26. Genome-wide associations for birth weight and correlations with adult disease

Author: Horikoshi, M, Beaumont, RN, Day, FR, Warrington, NM, Kooijman, MN, Fernandez-Tajes, J, Feenstra, B, Van Zuydam, NR, Gaulton, KJ, Grarup, N, Bradfield, JP, Strachan, DP, Li-Gao, R, Ahluwalia, TS, Kreiner, E, Rueedi, R, Lyytikäinen, L-P, Cousminer, DL, Wu, Y, Thiering, E, Wang, CA, Have, CT, Hottenga, J-J, Vilor-Tejedor, N, Joshi, PK, Boh, ETH, Ntalla, I, Pitkänen, N, Mahajan, A, Van Leeuwen, EM, Joro, R, Lagou, V, Nodzenski, M, Diver, LA, Zondervan, KT, Bustamante, M, Marques-Vidal, P, Mercader, JM, Bennett, AJ, Rahmioglu, N, Nyholt, DR, Ma, RCW, Tam, CHT, Tam, WH, CHARGE Consortium Hematology Working Group, Ganesh, SK, Van Rooij, FJA, Jones, SE, Loh, P-R, Ruth, KS, Tuke, MA, Tyrrell, J, Wood, AR, Yaghootkar, H, Scholtens, DM, Paternoster, L, Prokopenko, I, Kovacs, P, Atalay, M, Willems, SM, Panoutsopoulou, K, Wang, X, Carstensen, L, Geller, F, Schraut, KE, Murcia, M, Van Beijsterveldt, CEM, Willemsen, G, Appel, EVR, Fonvig, CE, Trier, C, Tiesler, CMT, Standl, M, Kutalik, Z, Bonàs-Guarch, S, Hougaard, DM, Sánchez, F, Torrents, D, Waage, J, Hollegaard, MV, De Haan, HG, Rosendaal, FR, Medina-Gomez, C, Ring, SM, Hemani, G, McMahon, G, Robertson, NR, Groves, CJ, Langenberg, C, Luan, J, Scott, RA, Zhao, JH, Mentch, FD, MacKenzie, SM, Reynolds, RM, Early Growth Genetics (EGG) Consortium, Lowe, WL, Tönjes, A, Stumvoll, M, Lindi, V, Lakka, TA, Van Duijn, CM, Kiess, W, Körner, A, Sørensen, TIA, Niinikoski, H, Pahkala, K, Raitakari, OT, Zeggini, E, Dedoussis, GV, Teo, Y-Y, Saw, S-M, Melbye, M, Campbell, H, Wilson, JF, Vrijheid, M, De Geus, EJCN, Boomsma, DI, Kadarmideen, HN, Holm, J-C, Hansen, T, Sebert, S, Hattersley, AT, Beilin, LJ, Newnham, JP, Pennell, CE, Heinrich, J, Adair, LS, Borja, JB, Mohlke, KL, Eriksson, JG, Widén, E, Kähönen, M, Viikari, JS, Lehtimäki, T, Vollenweider, P, Bønnelykke, K, Bisgaard, H, Mook-Kanamori, DO, Hofman, A, Rivadeneira, F, Uitterlinden, AG, Pisinger, C, Pedersen, O, Power, C, Hyppönen, E, Wareham, NJ, Hakonarson, H, Davies, E, Walker, BR, Jaddoe, VWV, Järvelin, M-R, Grant, SFA, Vaag, AA, Lawlor, DA, Frayling, TM, Smith, GD, Morris, AP, Ong, KK, Felix, JF, Timpson, NJ, Perry, JRB, Evans, DM, McCarthy, MI, and Freathy, RM
Subjects: quantitative trait, hypertension, intrauterine growth, genome-wide association studies, metabolic disorders, 3. Good health
Abstract: Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$ < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$ = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$ = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$ = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

27. Dissecting Causal Pathways Using Mendelian Randomization with Summarized Genetic Data: Application to Age at Menarche and Risk of Breast Cancer

Author: Burgess, S, Thompson, DJ, Rees, JMB, Day, FR, Perry, and Ong, K
Subjects: 2. Zero hunger, Mendelian randomization, direct effect, causal inference, mediation analysis, 3. Good health, instrumental variable
Abstract: Mendelian randomization is the use of genetic variants as instrumental variables to estimate causal effects of risk factors on outcomes. The total causal effect of a risk factor is the change in the outcome resulting from intervening on the risk factor. This total causal effect may potentially encompass multiple mediating mechanisms. For a proposed mediator, the direct effect of the risk factor is the change in the outcome resulting from a change in the risk factor, keeping the mediator constant. A difference between the total effect and the direct effect indicates that the causal pathway from the risk factor to the outcome acts at least in part via the mediator (an indirect effect). Here, we show that Mendelian randomization estimates of total and direct effects can be obtained using summarized data on genetic associations with the risk factor, mediator, and outcome, potentially from different data sources. We perform simulations to test the validity of this approach when there is unmeasured confounding and/or bidirectional effects between the risk factor and mediator. We illustrate this method using the relationship between age at menarche and risk of breast cancer, with body mass index (BMI) as a potential mediator. We show an inverse direct causal effect of age at menarche on risk of breast cancer (independent of BMI), and a positive indirect effect via BMI. In conclusion, multivariable Mendelian randomization using summarized genetic data provides a rapid and accessible analytic strategy that can be undertaken using publicly available data to better understand causal mechanisms.

28. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

Author: Willems, SM, Wright, DJ, Day, FR, Trajanoska, K, Joshi, PK, Morris, JA, Matteini, AM, Garton, FC, Grarup, N, Oskolkov, N, Thalamuthu, A, Mangino, M, Liu, J, Demirkan, A, Lek, M, Xu, L, Wang, G, Oldmeadow, C, Gaulton, KJ, Lotta, LA, Miyamoto-Mikami, E, Rivas, MA, White, T, Loh, P-R, Aadahl, M, Amin, N, Attia, Austin, K, Benyamin, B, Brage, S, Cheng, Y-C, Cięszczyk, P, Derave, W, Eriksson, K-F, Eynon, N, Linneberg, A, Lucia, A, Massidda, M, Mitchell, BD, Miyachi, M, Murakami, H, Padmanabhan, S, Pandey, A, Papadimitriou, I, Rajpal, DK, Sale, C, Schnurr, TM, Sessa, F, Shrine, N, Tobin, MD, Varley, I, Wain, LV, Wray, NR, Lindgren, CM, MacArthur, DG, Waterworth, D, McCarthy, MI, Pedersen, O, Khaw, K-T, Kiel, DP, Pitsiladis, Y, Fuku, N, Franks, PW, North, KN, Van Duijn, CM, Mather, KA, Hansen, T, Hansson, O, Spector, T, Murabito, JM, Richards, JB, Rivadeneira, F, Langenberg, C, Perry, JRB, Wareham, NJ, and Scott, RA
Subjects: Adult, Male, Hand Strength, Membrane Proteins, Nuclear Proteins, Middle Aged, Transforming Growth Factor alpha, Hand, Polymorphism, Single Nucleotide, Actins, United Kingdom, White People, 3. Good health, Neoplasm Proteins, Cohort Studies, Repressor Proteins, Genetics, Population, Genetic Loci, Humans, Female, Aged, Genome-Wide Association Study
Abstract: Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P

29. Into every life a little Zen must fall. A Christian philosopher looks to Alan Watts and the East. Alan Keightley.

Author: Day, Fr Michael, primary
Published: 1988
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30. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Author: Zhaoming Wang, André Scherag, James F. Wilson, Nancy L. Heard-Costa, Ingrid B. Borecki, Sang Hong Lee, Veronique Vitart, Zoltán Kutalik, Jeffrey R. O'Connell, Mieke D. Trip, Lu Qi, Peter Vollenweider, Jennifer L. Bragg-Gresham, Davide Gentilini, Kees Hovingh, Lynda M. Rose, Carolin Pütter, Martin Farrall, Albert V. Smith, Nicholas G. Martin, Tõnu Esko, David J. Hunter, Georg Homuth, Liming Liang, Yudi Pawitan, Winfried März, George Dedoussis, Irene Mateo Leach, Nicholas J. Wareham, Lars Lind, Thomas Illig, Andrew P. Morris, Daniele Cusi, Jouke-Jan Hottenga, Tove Fall, Themistocles L. Assimes, Massimo Mangino, Dmitry Shungin, Kari Stefansson, Anne U. Jackson, Inês Barroso, Sarah E. Medland, Lude Franke, Karen L. Mohlke, Folkert W. Asselbergs, Sarah E. Hunt, Gudmar Thorleifsson, Pablo V. Gejman, Serena Sanna, Mark I. McCarthy, David M. Evans, Joel N. Hirschhorn, Alan F. Wright, Sarah H. Wild, Patricia B. Munroe, Marcel Bruinenberg, Gonneke Willemsen, Ulf de Faire, Markku Laakso, Marja-Liisa Lokki, Andrew C. Heath, Jing Hua Zhao, Lavinia Paternoster, Jana V. van Vliet-Ostaptchouk, Sailaja Vedantam, Danyu Lin, Eric E. Schadt, Stefano Signorini, Harald Grallert, Tsegaselassie Workalemahu, Jonathan Tyrer, Albert Hofman, George Nicholson, Patrik K. E. Magnusson, Arthur W. Musk, Jian Yang, Vilmundur Gudnason, Robert C. Kaplan, Panos Deloukas, Nilesh J. Samani, Inke R. König, Frank B. Hu, Paul M. Ridker, Tamara B. Harris, Bruce H. R. Wolffenbuttel, Ellen A. Nohr, Sarah Edkins, Lambertus A. Kiemeney, Anke Hinney, Eric Boerwinkle, Klaus Stark, Ben A. Oostra, Barbara Thorand, Unnur Thorsteinsdottir, Meena Kumari, Evelin Mihailov, Caroline S. Fox, Michael Boehnke, Aroon D. Hingorani, Jonathan Stephens, Kathleen Stirrups, Inga Prokopenko, Anke Tönjes, Lili Milani, John Beilby, Carlos Iribarren, Kari E. North, Cécile Lecoeur, So-Youn Shin, Marjo-Riitta Järvelin, Matti Uusitupa, Åsa Johansson, Nancy L. Pedersen, Krista Fischer, Fernando Rivadeneira, Wolfgang Koenig, Fredrik Karpe, Antti Jula, Lindsay L. Waite, Gérard Waeber, Mustafa Atalay, Heribert Schunkert, Narisu Narisu, Sita H. Vermeulen, Bernhard R. Winkelmann, Guo Li, Anders Hamsten, Elizabeth K. Speliotes, Ivonne Jarick, Sirkka Keinänen-Kiukaanniemi, L. Adrienne Cupples, Ruth J. F. Loos, Martina Müller-Nurasyid, David-Alexandre Trégouët, Claudia Langenberg, Willem H. Ouwehand, Julius S. Ngwa, Jennifer E. Huffman, H-Erich Wichmann, Amy J. Swift, Marco M Ferrario, Leif Groop, Henrik Grönberg, Peter M. Visscher, Claes Ohlsson, Markku S. Nieminen, Aparna Radhakrishnan, Harold Snieder, Devin Absher, Albertine J. Oldehinkel, Erik Ingelsson, Anna Maria Di Blasio, M. Carola Zillikens, Veikko Salomaa, Colin N. A. Palmer, Lori L. Bonnycastle, Teresa Ferreira, Ronald P. Stolk, Annette Peters, Philippe Froguel, Michael Stumvoll, David Schlessinger, Maria Dimitriou, Timo Saaristo, Cristen J. Willer, Jarmo Virtamo, Jorma Viikari, Alena Stančáková, Mika Kivimäki, Paolo Brambilla, Jaakko Tuomilehto, Dorret I. Boomsma, Harry Campbell, Jianjun Liu, Daniel I. Chasman, Gonçalo R. Abecasis, Ilja M. Nolte, Karl-Heinz Jöckel, Reedik Mägi, Pamela A. F. Madden, Jaana Laitinen, Sonja I. Berndt, Frank Kee, Marcus E. Kleber, Jacqueline C.M. Witteman, Jouko Saramies, Francis S. Collins, Johan G. Eriksson, Melanie M. van der Klauw, Yi-Juan Hu, John F. Peden, Markus Perola, Henri Wallaschofski, Jean Ferrières, Elena Tremoli, Marjolein J. Peters, Olli T. Raitakari, Claudia Lamina, Sekar Kathiresan, Mary F. Feitosa, Diana Kuh, Tim D. Spector, Paul W. Franks, Gerjan Navis, Martin den Heijer, Christian Gieger, Kevin B. Jacobs, Andrea Ganna, Timothy M. Frayling, Iris M. Heid, Bernhard O. Boehm, Eleanor Wheeler, Sonali Pechlivanis, Miriam F. Moffatt, Brenda W.J.H. Penninx, Anna-Liisa Hartikainen, Augusto Rendon, Stefan Schreiber, Stephen J. Chanock, Andrew R. Wood, Jianxin Shi, Najaf Amin, Lenore J. Launer, Michael A. Province, Jeanette Erdmann, Mattias Lorentzon, Hugh Watkins, Johanna Kuusisto, John-Olov Jansson, David P. Strachan, Anne E. Justice, Toby Johnson, Cornelia M. van Duijn, Niina Eklund, Samuli Ripatti, Aarno Palotie, Aldi T. Kraja, Michael Preuss, Rona J. Strawbridge, Ozren Polasek, Elisabeth Widen, Barbara McKnight, Mariano Dei, Vincent Mooser, Josine L. Min, Caroline Hayward, Mika Kähönen, Peter P. Pramstaller, Femmie de Vegt, Rainer Rauramaa, Douglas F. Levinson, Diana Marek, Antonio Liuzzi, Stefan Gustafsson, Andrew A. Hicks, Gemma Cadby, Damien C. Croteau-Chonka, Mark J. Caulfield, Boris Skrobek, Lyle J. Palmer, Alexander Teumer, Ken K. Ong, Ulf Gyllensten, Anneli Pouta, Anuj Goel, Eva Albrecht, Kristian Hveem, Inger Njølstad, David Meyre, Ida Surakka, Francesca Frau, Paolo Manunta, Sabine Schipf, Carolina Medina-Gomez, Kay-Tee Khaw, Alan R. Sanders, Thorkild I. A. Sørensen, André G. Uitterlinden, Alistair S. Hall, Felix R. Day, Karol Estrada, Jennifer G. Sambrook, Eirini V. Theodoraki, Valgerdur Steinthorsdottir, Cecilia M. Lindgren, Talin Haritunian, Benjamin M. Neale, Juha Sinisalo, Kati Kristiansson, Thomas W. Winkler, Pim van der Harst, Peter S. Chines, Joyce B. J. van Meurs, Wendy L. McArdle, Andrew Wong, Grant W. Montgomery, Terho Lehtimäki, Igor Rudan, Keri L. Monda, John M. C. Connell, Jian'an Luan, Per Hall, Joshua C. Randall, Anthony J. Balmforth, Chris Power, Philippe Amouyel, Andres Metspalu, Johannes Hebebrand, Andrew D. Morris, Jaana Lindström, Liesbeth Vandenput, William O.C.M. Cookson, Hanneke Basart, Stavroula Kanoni, Elina Hyppönen, Christian Hengstenberg, Thomas W. Mühleisen, Kari Kuulasmaa, Timo A. Lakka, Nicole Soranzo, Bruce M. Psaty, Antony P. Attwood, Epidemiology, Clinical Genetics, Surgery, Erasmus School of Social and Behavioural Sciences, Public Health, Internal Medicine, Immunology, Child and Adolescent Psychiatry / Psychology, Internal medicine, Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Lifestyle, overweight and diabetes, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Other departments, Vascular Medicine, Biological Psychology, Cognitive Psychology, AIMMS, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Life Course Epidemiology (LCE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Medical Research Council (MRC), Berndt, Sonja I, Gustafsson, Stefan, Mägi, Reedik, Ganna, Andrea, Lee, Sang Hong, Hyppönen, Elina Tuulikki, Ingelsson, Erik, Berndt, Si, Feitosa, Mf, Justice, Ae, Monda, Kl, CROTEAU CHONKA, Dc, Day, Fr, Jackson, Au, Randall, Jc, Willer, Cj, Winkler, Tw, Wood, Ar, Hu, Yj, Lee, Sh, Lin, Dy, Min, Jl, Neale, Bm, BRAGG GRESHAM, Jl, DEN HEIJER, M, Hottenga, Jj, Huffman, Je, Johansson, A, Kleber, Me, König, Ir, Mcardle, Wl, MEDINA GOMEZ, C, MÜLLER NURASYID, M, Nolte, Im, Peters, Mj, Rose, Lm, Smith, Av, Strawbridge, Rj, Trip, Md, VAN VLIET OSTAPTCHOUK, Jv, Waite, Ll, Zhao, Jh, Asselbergs, Fw, Attwood, Ap, Balmforth, Aj, Bonnycastle, Ll, Chasman, Di, Connell, Jm, Cookson, Wo, DE FAIRE, U, DE VEGT, F, Evans, Dm, Ferrario, Mm, Gejman, Pv, Hartikainen, Al, HEARD COSTA, Nl, Heath, Ac, Hu, Fb, Hunt, Se, Jacobs, Kb, Jansson, Jo, Khaw, Kt, Kraja, At, Laitinen, Jh, Lakka, Ta, Launer, Lj, Lokki, Ml, Madden, Pa, Magnusson, Pk, Manunta, Paolo, MATEO LEACH, I, Medland, Se, Montgomery, Gw, Mühleisen, Tw, Munroe, Pb, Musk, Aw, Nohr, Ea, Ong, Kk, Oostra, Ba, Palmer, Cn, Peden, Jf, Pramstaller, Pp, Saaristo, Te, Sambrook, Jg, Sanders, Ar, Shin, Sy, Stephens, Jc, Stolk, Rp, Swift, Aj, Theodoraki, Ev, Tregouet, Da, VAN DER KLAUW, Mm, VAN MEURS, Jb, Vermeulen, Sh, Wild, Sh, Winkelmann, Br, Witteman, Jc, Wolffenbuttel, Bh, Wright, Af, Zillikens, Mc, Boehm, Bo, Boomsma, Di, Caulfield, Mj, Chanock, Sj, Cupples, La, Dedoussis, Gv, Eriksson, Jg, Franks, Pw, Harris, Tb, Hicks, Aa, Hovingh, Kg, Jarvelin, Mr, Jöckel, Kh, KEINANEN KIUKAANNIEMI, Sm, Kiemeney, La, Levinson, Df, Martin, Ng, Morris, Ad, Oldehinkel, Aj, Ouwehand, Wh, Palmer, Lj, Province, Ma, Psaty, Bm, Ridker, Pm, Samani, Nj, Sørensen, Ti, Spector, Td, Uitterlinden, Ag, VAN DER HARST, P, Wareham, Nj, Wichmann, He, Wilson, Jf, Abecasis, Gr, Assimes, Tl, Borecki, Ib, Groop, Lc, Heid, Im, Kaplan, Rc, Moffatt, Mf, Mohlke, Kl, O'Connell, Jr, Schadt, Ee, Strachan, Dp, VAN DUIJN, Cm, Visscher, Pm, DI BLASIO, Am, Hirschhorn, Jn, Lindgren, Cm, Morris, Ap, Mccarthy, Mi, Speliotes, Ek, North, Ke, Loos, Rj, and Ingelsson, E.
Subjects: Netherlands Twin Register (NTR), Linkage disequilibrium, SORTILIN, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Medizin, Genome-wide association study, Aetiology, screening and detection [ONCOL 5], polymorphism, Body Mass Index, 0302 clinical medicine, Missing heritability problem, MISSING HERITABILITY, EXTREME OBESITY, CONFER RISK, POPULATION, Genetics & Heredity, 2. Zero hunger, Genetics, Medical And Health Sciences, 0303 health sciences, education.field_of_study, Anthropometry, COMMON VARIANTS, Single Nucleotide, ASSOCIATION, Biological Sciences, Anthropometry, Body Height, genetics, Body Mass Index, Case-Control Studies, European Continental Ancestry Group, genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Obesity, genetics, Phenotype, Polymorphism, genetics, Quantitative Trait Loci, Waist-Hip Ratio, Phenotype, Life Sciences & Biomedicine, EXPRESSION, Genotype, Missing heritabillity, Population, European Continental Ancestry Group, Quantitative Trait Loci, EARLY-ONSET, Genomics, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, Article, White People, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, Obesity, body height/genetics, Polymorphism, Allele, Genetik, education, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 030304 developmental biology, Science & Technology, Waist-Hip Ratio, BMI, height, WHR, obesity, GWS, ta3121, Genetic architecture, Body Height, BODY-MASS INDEX, Case-Control Studies, gene, stature, height, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups. © 2013 Nature America, Inc. All rights reserved.
Published: 2013
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31. Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

Author: Kentistou KA, Lim BEM, Kaisinger LR, Steinthorsdottir V, Sharp LN, Patel KA, Tragante V, Hawkes G, Gardner EJ, Olafsdottir T, Wood AR, Zhao Y, Thorleifsson G, Day FR, Ozanne SE, Hattersley AT, O'Rahilly S, Stefansson K, Ong KK, Beaumont RN, Perry JRB, and Freathy RM
Subjects: Humans, Female, Pregnancy, Male, Adult, Receptor, IGF Type 1 genetics, Receptor, IGF Type 1 metabolism, Somatomedins metabolism, Somatomedins genetics, Infant, Newborn, Nitric Oxide Synthase Type III genetics, Nitric Oxide Synthase Type III metabolism, Exome Sequencing, Genome-Wide Association Study, Fetus metabolism, Insulin-Like Peptides, Birth Weight genetics, Placenta metabolism, Adipose Tissue metabolism, Signal Transduction genetics, PPAR gamma genetics, PPAR gamma metabolism
Abstract: Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests. We identify 9 genes; 5 with fetal-only effects on birth weight, 1 with maternal-only effects, 3 with both, and observe directionally concordant associations in an independent sample. Four of the genes were previously implicated by GWAS of birth weight. IGF1R and PAPPA2 (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling. PPARG, INHBE and ACVR1C (fetal-acting) are involved in adipose tissue regulation, and the latter two also show associations with favourable adiposity patterns in adults. We highlight the dual role of PPARG (fetal-acting) in adipocyte differentiation and placental angiogenesis. NOS3 (fetal and maternal-acting), NRK (fetal), and ADAMTS8 (maternal-acting) have been implicated in placental function and hypertension. To conclude, our analysis of rare coding variants identifies regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, and further evidence for the role of insulin-like growth factors., Competing Interests: Competing interests: J.R.B.P. and E.J.G. are employees/shareholders of Insmed. J.R.B.P. also receives research funding from GSK and consultancy fees from WW International. Y.Z. is a UK University worker at GSK. S.O. has undertaken remunerated consultancy work for Pfizer, Third Rock Ventures, AstraZeneca, NorthSea Therapeutics and Courage Therapeutics. V.S., V.T., T.O., G.T., and K.S. are employees of deCODE genetics, a subsidiary of Amgen. The remaining authors declare no competing interests., (© 2025. The Author(s).)
Published: 2025
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32. Genetic Variants Associated With Preeclampsia and Maternal Serum sFLT1 Levels.

Author: Mack JA, Sovio U, Day FR, Gaccioli F, Cook E, Bayzid N, Cotic M, Dunton N, Madhan G, Motsinger-Reif A, Perry JRB, Charnock-Jones DS, and Smith GCS
Abstract: Background: Elevated maternal serum sFLT1 (soluble fms-like tyrosine kinase 1) has a key role in the pathophysiology of preeclampsia. We sought to determine the relationship between the maternal and fetal genome and maternal levels of sFLT1 at 12, 20, 28, and 36 weeks of gestational age (wkGA)., Methods: We studied a prospective cohort of nulliparous women (3968 mother-child pairs). We related maternal and fetal genotype to the adjusted sFLT1 Z score and sFLT1:placental growth factor (PlGF) ratio Z score at each wkGA and the change in the Z score between 28 and 36 wkGA (Δ36-28). We studied genetic variants from a previous fetal genome-wide association study of preeclampsia and an externally defined polygenic score from a maternal genome-wide association study of preeclampsia., Results: Four variants from the fetal preeclampsia genome-wide association study were positively associated with sFLT1 and sFLT1:PlGF Z score at 36 wkGA, and FLT1 enhancer single-nucleotide polymorphisms were associated with increased Δ36-28 of sFLT1. The associations were specific for the fetal genome or stronger for the fetal than the maternal genome. An increased risk of preeclampsia based on the maternal polygenic score for preeclampsia was associated with lower levels of sFLT1 and sFLT1:PlGF ratio in the first trimester and a greater Δ36-28 for sFLT1., Conclusions: The current data are consistent with a causal association between sFLT1 released by the placenta in late pregnancy and the pathophysiology of preeclampsia. The data are also consistent with maternal components to the protective effect of high sFLT1 in the first trimester and the rise in third-trimester sFLT1 levels and preeclampsia.
Published: 2024
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33. Likely causal effects of insulin resistance and IGF-1 bioaction on childhood and adult adiposity: a Mendelian randomization study.

Author: Olwi DI, Kaisinger LR, Kentistou KA, Vaudel M, Stankovic S, Njølstad PR, Johansson S, Perry JRB, Day FR, and Ong KK
Subjects: Humans, Child, Adult, Male, Female, Body Mass Index, Insulin blood, Insulin metabolism, Pediatric Obesity genetics, Pediatric Obesity epidemiology, Mendelian Randomization Analysis, Insulin Resistance genetics, Adiposity genetics, Insulin-Like Growth Factor I metabolism
Abstract: Background: Circulating insulin and insulin-like growth factor-1 (IGF-1) concentrations are positively correlated with adiposity. However, the causal effects of insulin and IGF-1 on adiposity are unclear., Methods: We performed two-sample Mendelian randomization analyses to estimate the likely causal effects of fasting insulin and IGF-1 on relative childhood adiposity and adult body mass index (BMI). To improve accuracy and biological interpretation, we applied Steiger filtering (to avoid reverse causality) and 'biological effect' filtering of fasting insulin and IGF-1 associated variants., Results: Fasting insulin-increasing alleles (35 variants also associated with higher fasting glucose, indicative of insulin resistance) were associated with lower relative childhood adiposity (P = 3.8 × 10 -3 ) and lower adult BMI (P = 1.4 × 10 -5 ). IGF-1-increasing alleles also associated with taller childhood height (351 variants indicative of greater IGF-1 bioaction) showed no association with relative childhood adiposity (P = 0.077) or adult BMI (P = 0.562). Conversely, IGF-1-increasing alleles also associated with shorter childhood height (306 variants indicative of IGF-1 resistance) were associated with lower relative childhood adiposity (P = 6.7 × 10 -3 ), but effects on adult BMI were inconclusive., Conclusions: Genetic causal modelling indicates negative effects of insulin resistance on childhood and adult adiposity, and negative effects of IGF-1 resistance on childhood adiposity. Our findings demonstrate the need to distinguish between bioaction and resistance when modelling variants associated with biomarker concentrations., (© 2024. The Author(s).)
Published: 2024
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34. Genetic links between ovarian ageing, cancer risk and de novo mutation rates.

Author: Stankovic S, Shekari S, Huang QQ, Gardner EJ, Ivarsdottir EV, Owens NDL, Mavaddat N, Azad A, Hawkes G, Kentistou KA, Beaumont RN, Day FR, Zhao Y, Jonsson H, Rafnar T, Tragante V, Sveinbjornsson G, Oddsson A, Styrkarsdottir U, Gudmundsson J, Stacey SN, Gudbjartsson DF, Kennedy K, Wood AR, Weedon MN, Ong KK, Wright CF, Hoffmann ER, Sulem P, Hurles ME, Ruth KS, Martin HC, Stefansson K, Perry JRB, and Murray A
Subjects: Adult, Female, Humans, Male, Middle Aged, DNA Damage genetics, Fertility genetics, Genetic Variation genetics, Genome, Human genetics, Germ-Line Mutation genetics, Menarche genetics, Time Factors, UK Biobank, United Kingdom epidemiology, Aging genetics, Aging pathology, Genetic Predisposition to Disease genetics, Menopause genetics, Mutation Rate, Neoplasms genetics, Ovary metabolism, Ovary pathology
Abstract: Human genetic studies of common variants have provided substantial insight into the biological mechanisms that govern ovarian ageing 1 . Here we report analyses of rare protein-coding variants in 106,973 women from the UK Biobank study, implicating genes with effects around five times larger than previously found for common variants (ETAA1, ZNF518A, PNPLA8, PALB2 and SAMHD1). The SAMHD1 association reinforces the link between ovarian ageing and cancer susceptibility 1 , with damaging germline variants being associated with extended reproductive lifespan and increased all-cause cancer risk in both men and women. Protein-truncating variants in ZNF518A are associated with shorter reproductive lifespan-that is, earlier age at menopause (by 5.61 years) and later age at menarche (by 0.56 years). Finally, using 8,089 sequenced trios from the 100,000 Genomes Project (100kGP), we observe that common genetic variants associated with earlier ovarian ageing associate with an increased rate of maternally derived de novo mutations. Although we were unable to replicate the finding in independent samples from the deCODE study, it is consistent with the expected role of DNA damage response genes in maintaining the genetic integrity of germ cells. This study provides evidence of genetic links between age of menopause and cancer risk., (© 2024. The Author(s).)
Published: 2024
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35. Publisher Correction: Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Author: Kentistou KA, Kaisinger LR, Stankovic S, Vaudel M, Mendes de Oliveira E, Messina A, Walters RG, Liu X, Busch AS, Helgason H, Thompson DJ, Santoni F, Petricek KM, Zouaghi Y, Huang-Doran I, Gudbjartsson DF, Bratland E, Lin K, Gardner EJ, Zhao Y, Jia RY, Terao C, Riggan MJ, Bolla MK, Yazdanpanah M, Yazdanpanah N, Bradfield JP, Broer L, Campbell A, Chasman DI, Cousminer DL, Franceschini N, Franke LH, Girotto G, He C, Järvelin MR, Joshi PK, Kamatani Y, Karlsson R, Luan J, Lunetta KL, Mägi R, Mangino M, Medland SE, Meisinger C, Noordam R, Nutile T, Concas MP, Polašek O, Porcu E, Ring SM, Sala C, Smith AV, Tanaka T, van der Most PJ, Vitart V, Wang CA, Willemsen G, Zygmunt M, Ahearn TU, Andrulis IL, Anton-Culver H, Antoniou AC, Auer PL, Barnes CLK, Beckmann MW, Berrington de Gonzalez A, Bogdanova NV, Bojesen SE, Brenner H, Buring JE, Canzian F, Chang-Claude J, Couch FJ, Cox A, Crisponi L, Czene K, Daly MB, Demerath EW, Dennis J, Devilee P, De Vivo I, Dörk T, Dunning AM, Dwek M, Eriksson JG, Fasching PA, Fernandez-Rhodes L, Ferreli L, Fletcher O, Gago-Dominguez M, García-Closas M, García-Sáenz JA, González-Neira A, Grallert H, Guénel P, Haiman CA, Hall P, Hamann U, Hakonarson H, Hart RJ, Hickey M, Hooning MJ, Hoppe R, Hopper JL, Hottenga JJ, Hu FB, Huebner H, Hunter DJ, Jernström H, John EM, Karasik D, Khusnutdinova EK, Kristensen VN, Lacey JV, Lambrechts D, Launer LJ, Lind PA, Lindblom A, Magnusson PKE, Mannermaa A, McCarthy MI, Meitinger T, Menni C, Michailidou K, Millwood IY, Milne RL, Montgomery GW, Nevanlinna H, Nolte IM, Nyholt DR, Obi N, O'Brien KM, Offit K, Oldehinkel AJ, Ostrowski SR, Palotie A, Pedersen OB, Peters A, Pianigiani G, Plaseska-Karanfilska D, Pouta A, Pozarickij A, Radice P, Rennert G, Rosendaal FR, Ruggiero D, Saloustros E, Sandler DP, Schipf S, Schmidt CO, Schmidt MK, Small K, Spedicati B, Stampfer M, Stone J, Tamimi RM, Teras LR, Tikkanen E, Turman C, Vachon CM, Wang Q, Winqvist R, Wolk A, Zemel BS, Zheng W, van Dijk KW, Alizadeh BZ, Bandinelli S, Boerwinkle E, Boomsma DI, Ciullo M, Chenevix-Trench G, Cucca F, Esko T, Gieger C, Grant SFA, Gudnason V, Hayward C, Kolčić I, Kraft P, Lawlor DA, Martin NG, Nøhr EA, Pedersen NL, Pennell CE, Ridker PM, Robino A, Snieder H, Sovio U, Spector TD, Stöckl D, Sudlow C, Timpson NJ, Toniolo D, Uitterlinden A, Ulivi S, Völzke H, Wareham NJ, Widen E, Wilson JF, Pharoah PDP, Li L, Easton DF, Njølstad PR, Sulem P, Murabito JM, Murray A, Manousaki D, Juul A, Erikstrup C, Stefansson K, Horikoshi M, Chen Z, Farooqi IS, Pitteloud N, Johansson S, Day FR, Perry JRB, and Ong KK
Published: 2024
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36. Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Author: Kentistou KA, Kaisinger LR, Stankovic S, Vaudel M, Mendes de Oliveira E, Messina A, Walters RG, Liu X, Busch AS, Helgason H, Thompson DJ, Santoni F, Petricek KM, Zouaghi Y, Huang-Doran I, Gudbjartsson DF, Bratland E, Lin K, Gardner EJ, Zhao Y, Jia RY, Terao C, Riggan MJ, Bolla MK, Yazdanpanah M, Yazdanpanah N, Bradfield JP, Broer L, Campbell A, Chasman DI, Cousminer DL, Franceschini N, Franke LH, Girotto G, He C, Järvelin MR, Joshi PK, Kamatani Y, Karlsson R, Luan J, Lunetta KL, Mägi R, Mangino M, Medland SE, Meisinger C, Noordam R, Nutile T, Concas MP, Polašek O, Porcu E, Ring SM, Sala C, Smith AV, Tanaka T, van der Most PJ, Vitart V, Wang CA, Willemsen G, Zygmunt M, Ahearn TU, Andrulis IL, Anton-Culver H, Antoniou AC, Auer PL, Barnes CLK, Beckmann MW, Berrington de Gonzalez A, Bogdanova NV, Bojesen SE, Brenner H, Buring JE, Canzian F, Chang-Claude J, Couch FJ, Cox A, Crisponi L, Czene K, Daly MB, Demerath EW, Dennis J, Devilee P, De Vivo I, Dörk T, Dunning AM, Dwek M, Eriksson JG, Fasching PA, Fernandez-Rhodes L, Ferreli L, Fletcher O, Gago-Dominguez M, García-Closas M, García-Sáenz JA, González-Neira A, Grallert H, Guénel P, Haiman CA, Hall P, Hamann U, Hakonarson H, Hart RJ, Hickey M, Hooning MJ, Hoppe R, Hopper JL, Hottenga JJ, Hu FB, Huebner H, Hunter DJ, Jernström H, John EM, Karasik D, Khusnutdinova EK, Kristensen VN, Lacey JV, Lambrechts D, Launer LJ, Lind PA, Lindblom A, Magnusson PKE, Mannermaa A, McCarthy MI, Meitinger T, Menni C, Michailidou K, Millwood IY, Milne RL, Montgomery GW, Nevanlinna H, Nolte IM, Nyholt DR, Obi N, O'Brien KM, Offit K, Oldehinkel AJ, Ostrowski SR, Palotie A, Pedersen OB, Peters A, Pianigiani G, Plaseska-Karanfilska D, Pouta A, Pozarickij A, Radice P, Rennert G, Rosendaal FR, Ruggiero D, Saloustros E, Sandler DP, Schipf S, Schmidt CO, Schmidt MK, Small K, Spedicati B, Stampfer M, Stone J, Tamimi RM, Teras LR, Tikkanen E, Turman C, Vachon CM, Wang Q, Winqvist R, Wolk A, Zemel BS, Zheng W, van Dijk KW, Alizadeh BZ, Bandinelli S, Boerwinkle E, Boomsma DI, Ciullo M, Chenevix-Trench G, Cucca F, Esko T, Gieger C, Grant SFA, Gudnason V, Hayward C, Kolčić I, Kraft P, Lawlor DA, Martin NG, Nøhr EA, Pedersen NL, Pennell CE, Ridker PM, Robino A, Snieder H, Sovio U, Spector TD, Stöckl D, Sudlow C, Timpson NJ, Toniolo D, Uitterlinden A, Ulivi S, Völzke H, Wareham NJ, Widen E, Wilson JF, Pharoah PDP, Li L, Easton DF, Njølstad PR, Sulem P, Murabito JM, Murray A, Manousaki D, Juul A, Erikstrup C, Stefansson K, Horikoshi M, Chen Z, Farooqi IS, Pitteloud N, Johansson S, Day FR, Perry JRB, and Ong KK
Subjects: Humans, Female, Animals, Multifactorial Inheritance genetics, Mice, Genome-Wide Association Study, Adolescent, Puberty, Precocious genetics, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled genetics, Puberty, Delayed genetics, Child, Menarche genetics, Puberty genetics, Gene Frequency
Abstract: Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease., (© 2024. The Author(s).)
Published: 2024
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37. Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

Author: Kentistou KA, Lim BEM, Kaisinger LR, Steinthorsdottir V, Sharp LN, Patel KA, Tragante V, Hawkes G, Gardner EJ, Olafsdottir T, Wood AR, Zhao Y, Thorleifsson G, Day FR, Ozanne SE, Hattersley AT, O'Rahilly S, Stefansson K, Ong KK, Beaumont RN, Perry JRB, and Freathy RM
Abstract: Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. Genome-wide association studies of birth weight have highlighted associated variants in more than 200 regions of the genome, but the causal genes are mostly unknown. Rare genetic variants with robust evidence of association are more likely to point to causal genes, but to date, only a few rare variants are known to influence birth weight. We aimed to identify genes that harbour rare variants that impact birth weight when carried by either the fetus or the mother, by analysing whole exome sequence data in UK Biobank participants. We annotated rare (minor allele frequency <0.1%) protein-truncating or high impact missense variants on whole exome sequence data in up to 234,675 participants with data on their own birth weight (fetal variants), and up to 181,883 mothers who reported the birth weight of their first child (maternal variants). Variants within each gene were collapsed to perform gene burden tests and for each associated gene, we compared the observed fetal and maternal effects. We identified 8 genes with evidence of rare fetal variant effects on birth weight, of which 2 also showed maternal effects. One additional gene showed evidence of maternal effects only. We observed 10/11 directionally concordant associations in an independent sample of up to 45,622 individuals (sign test P =0.01). Of the genes identified, IGF1R and PAPPA2 (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling. PPARG, INHBE and ACVR1C (all fetal-acting) have known roles in adipose tissue regulation and rare variants in the latter two also showed associations with favourable adiposity patterns in adults. We highlight the dual role of PPARG in both adipocyte differentiation and placental angiogenesis. NOS3, NRK, and ADAMTS8 (fetal and maternal-acting) have been implicated in both placental function and hypertension. Analysis of rare coding variants has identified regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, as well as further evidence for the role of insulin-like growth factors., Competing Interests: Competing interests J.R.B.P. and E.J.G. are employees/shareholders of Insmed. J.R.B.P. also receives research funding from GSK. Y.Z. is a UK University worker at GSK. S.O. has undertaken remunerated consultancy work for Pfizer, Third Rock Ventures, AstraZeneca, NorthSea Therapeutics and Courage Therapeutics. V.S., V.T., T.O., G.T., and K.S. are employees of deCODE genetics, a subsidiary of Amgen.
Published: 2024
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38. Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease.

Author: Zhao Y, Chukanova M, Kentistou KA, Fairhurst-Hunter Z, Siegert AM, Jia RY, Dowsett GKC, Gardner EJ, Lawler K, Day FR, Kaisinger LR, Tung YL, Lam BYH, Chen HC, Wang Q, Berumen-Campos J, Kuri-Morales P, Tapia-Conyer R, Alegre-Diaz J, Barroso I, Emberson J, Torres JM, Collins R, Saleheen D, Smith KR, Paul DS, Merkle F, Farooqi IS, Wareham NJ, Petrovski S, O'Rahilly S, Ong KK, Yeo GSH, and Perry JRB
Subjects: Adult, Humans, Adaptor Proteins, Signal Transducing genetics, Genetic Predisposition to Disease, Obesity complications, Obesity genetics, Proteomics, Diabetes Mellitus, Type 2 genetics, Induced Pluripotent Stem Cells, Liver Diseases, Nerve Tissue Proteins genetics
Abstract: Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN protein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large in BSN PTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity., (© 2024. The Author(s).)
Published: 2024
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39. Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry.

Author: Burns K, Mullin BH, Moolhuijsen LME, Laisk T, Tyrmi JS, Cui J, Actkins KV, Louwers YV, Davis LK, Dudbridge F, Azziz R, Goodarzi MO, Laivuori H, Mägi R, Visser JA, Laven JSE, Wilson SG, Day FR, and Stuckey BGA
Subjects: Female, Humans, Body Mass Index, Overweight genetics, Case-Control Studies, Obesity genetics, Genome-Wide Association Study, Polycystic Ovary Syndrome genetics, Polycystic Ovary Syndrome complications
Abstract: Background: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder with a substantial genetic component. However, the clinical manifestations of PCOS are heterogeneous with notable differences between lean and obese women, implying a different pathophysiology manifesting in differential body mass index (BMI). We performed a meta-analysis of genome-wide association study (GWAS) data from six well-characterised cohorts, using a case-control study design stratified by BMI, aiming to identify genetic variants associated with lean and overweight/obese PCOS subtypes., Results: The study comprised 254,588 women (5,937 cases and 248,651 controls) from individual studies performed in Australia, Estonia, Finland, the Netherlands and United States of America, and separated according to three BMI stratifications (lean, overweight and obese). Genome-wide association analyses were performed for each stratification within each cohort, with the data for each BMI group meta-analysed using METAL software. Almost half of the total study population (47%, n = 119,584) were of lean BMI (≤ 25 kg/m 2 ). Two genome-wide significant loci were identified for lean PCOS, led by rs12000707 within DENND1A (P = 1.55 × 10 -12 ) and rs2228260 within XBP1 (P = 3.68 × 10 -8 ). One additional locus, LINC02905, was highlighted as significantly associated with lean PCOS through gene-based analyses (P = 1.76 × 10 -6 ). There were no significant loci observed for the overweight or obese sub-strata when analysed separately, however, when these strata were combined, an association signal led by rs569675099 within DENND1A reached genome-wide significance (P = 3.22 × 10 -9 ) and a gene-based association was identified with ERBB4 (P = 1.59 × 10 -6 ). Nineteen of 28 signals identified in previous GWAS, were replicated with consistent allelic effect in the lean stratum. There were less replicated signals in the overweight and obese groups, and only 4 SNPs were replicated in each of the three BMI strata., Conclusions: Genetic variation at the XBP1, LINC02905 and ERBB4 loci were associated with PCOS within unique BMI strata, while DENND1A demonstrated associations across multiple strata, providing evidence of both distinct and shared genetic features between lean and overweight/obese PCOS-affected women. This study demonstrated that PCOS-affected women with contrasting body weight are not only phenotypically distinct but also show variation in genetic architecture; lean PCOS women typically display elevated gonadotrophin ratios, lower insulin resistance, higher androgen levels, including adrenal androgens, and more favourable lipid profiles. Overall, these findings add to the growing body of evidence supporting a genetic basis for PCOS as well as differences in genetic patterns relevant to PCOS BMI-subtype., (© 2024. Crown.)
Published: 2024
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40. Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study.

Author: Watts EL, Gonzales TI, Strain T, Saint-Maurice PF, Bishop DT, Chanock SJ, Johansson M, Keku TO, Le Marchand L, Moreno V, Newcomb PA, Newton CC, Pai RK, Purdue MP, Ulrich CM, Smith-Byrne K, Van Guelpen B, Day FR, Wijndaele K, Wareham NJ, Matthews CE, Moore SC, and Brage S
Subjects: Male, Humans, Biological Specimen Banks, UK Biobank, Risk Factors, Cardiorespiratory Fitness, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics, Colorectal Neoplasms diagnosis
Abstract: Background: The association of fitness with cancer risk is not clear., Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method., Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O 2 ⋅min -1 ⋅kg -1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73-0.89), colorectal (0.94, 0.90-0.99), and breast cancer (0.96, 0.92-0.99). In MR analyses, a 0.5 SD increase in genetically predicted O 2 ⋅min -1 ⋅kg -1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86-0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated., Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention., (© 2023. The Author(s).)
Published: 2024
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41. Associations of appetitive traits with growth velocities from infancy to childhood.

Author: Olwi DI, Day FR, Cheng TS, Olga L, Petry CJ, Hughes IA, Smith AD, and Ong KK
Subjects: Child, Humans, Infant, Adolescent, Adiposity, Emotions, Feeding Behavior, Obesity, Pleasure
Abstract: Several studies have reported associations between appetitive traits and weight gain during infancy or childhood, but none have directly compared these associations across both age periods. Here, we tested the associations between appetitive traits and growth velocities from birth to childhood. Appetitive trait data were collected using the Children's Eating Behaviour Questionnaire (CEBQ) in 149 children from the Cambridge Baby Growth Study at age 9-17 years. These participants also provided anthropometric measurements during infancy (birth, 3, 12, 18, and 24 months) and childhood (5 to 11 years). Standardized growth velocities (in weight, length/height, BMI, and body fat percentage) for 0-3 months, 3-24 months, and 24 months to childhood were estimated using individual linear-spline models. Associations between each of the eight CEBQ traits and each growth velocity were tested in separate multilevel linear regression models, adjusted for sex, age at CEBQ completion, and the corresponding birth measurement (weight, length, BMI, or body fat percentage). The three food-approach traits (food responsiveness, enjoyment of food and emotional overeating) were positively associated with infancy and childhood growth velocities in weight, BMI, and body fat percentage. By contrast, only one of the food-avoidant traits, satiety responsiveness, was negatively associated with all growth velocities. Significant associations were mostly of similar magnitude across all age periods. These findings reveal a broadly consistent relationship between appetitive traits with gains in weight and adiposity throughout infancy and childhood. Future interventions and strategies to prevent obesity may benefit from measuring appetitive traits in infants and children and targeting these as part of their programs., (© 2023. Springer Nature Limited.)
Published: 2023
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42. Large-scale exome sequence analysis identifies sex- and age-specific determinants of obesity.

Author: Kaisinger LR, Kentistou KA, Stankovic S, Gardner EJ, Day FR, Zhao Y, Mörseburg A, Carnie CJ, Zagnoli-Vieira G, Puddu F, Jackson SP, O'Rahilly S, Farooqi IS, Dearden L, Pantaleão LC, Ozanne SE, Ong KK, and Perry JRB
Abstract: Obesity contributes substantially to the global burden of disease and has a significant heritable component. Recent large-scale exome sequencing studies identified several genes in which rare, protein-coding variants have large effects on adult body mass index (BMI). Here we extended such work by performing sex-stratified associations in the UK Biobank study (N∼420,000). We identified genes in which rare heterozygous loss-of-function increases adult BMI in women ( DIDO1, PTPRG, and SLC12A5 ) and in men ( SLTM ), with effect sizes up to ∼8 kg/m 2 . This is complemented by analyses implicating rare variants in OBSCN and MADD for recalled childhood adiposity. The known functions of these genes, as well as findings of common variant genome-wide pathway enrichment analyses, suggest a role for neuron death, apoptosis, and DNA damage response mechanisms in the susceptibility to obesity across the life-course. These findings highlight the importance of considering sex-specific and life-course effects in the genetic regulation of obesity., Competing Interests: E.J.G., S.P.J., and J.R.B.P. are employees and shareholders of Adrestia Therapeutics Ltd., (© 2023 The Authors.)
Published: 2023
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43. Causal associations between cardiorespiratory fitness and type 2 diabetes.

Author: Cai L, Gonzales T, Wheeler E, Kerrison ND, Day FR, Langenberg C, Perry JRB, Brage S, and Wareham NJ
Subjects: Humans, Proteomics, Obesity, Risk Factors, Diabetes Mellitus, Type 2 genetics, Cardiorespiratory Fitness physiology
Abstract: Higher cardiorespiratory fitness is associated with lower risk of type 2 diabetes. However, the causality of this relationship and the biological mechanisms that underlie it are unclear. Here, we examine genetic determinants of cardiorespiratory fitness in 450k European-ancestry individuals in UK Biobank, by leveraging the genetic overlap between fitness measured by an exercise test and resting heart rate. We identified 160 fitness-associated loci which we validated in an independent cohort, the Fenland study. Gene-based analyses prioritised candidate genes, such as CACNA1C, SCN10A, MYH11 and MYH6, that are enriched in biological processes related to cardiac muscle development and muscle contractility. In a Mendelian Randomisation framework, we demonstrate that higher genetically predicted fitness is causally associated with lower risk of type 2 diabetes independent of adiposity. Integration with proteomic data identified N-terminal pro B-type natriuretic peptide, hepatocyte growth factor-like protein and sex hormone-binding globulin as potential mediators of this relationship. Collectively, our findings provide insights into the biological mechanisms underpinning cardiorespiratory fitness and highlight the importance of improving fitness for diabetes prevention., (© 2023. The Author(s).)
Published: 2023
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44. Penetrance of pathogenic genetic variants associated with premature ovarian insufficiency.

Author: Shekari S, Stankovic S, Gardner EJ, Hawkes G, Kentistou KA, Beaumont RN, Mörseburg A, Wood AR, Prague JK, Mishra GD, Day FR, Baptista J, Wright CF, Weedon MN, Hoffmann ER, Ruth KS, Ong KK, Perry JRB, and Murray A
Subjects: Female, Humans, Adult, Penetrance, Basic Helix-Loop-Helix Transcription Factors genetics, Primary Ovarian Insufficiency genetics, Primary Ovarian Insufficiency complications, Primary Ovarian Insufficiency pathology, Menopause, Premature genetics
Abstract: Premature ovarian insufficiency (POI) affects 1% of women and is a leading cause of infertility. It is often considered to be a monogenic disorder, with pathogenic variants in ~100 genes described in the literature. We sought to systematically evaluate the penetrance of variants in these genes using exome sequence data in 104,733 women from the UK Biobank, 2,231 (1.14%) of whom reported at natural menopause under the age of 40 years. We found limited evidence to support any previously reported autosomal dominant effect. For nearly all heterozygous effects on previously reported POI genes, we ruled out even modest penetrance, with 99.9% (13,699 out of 13,708) of all protein-truncating variants found in reproductively healthy women. We found evidence of haploinsufficiency effects in several genes, including TWNK (1.54 years earlier menopause, P = 1.59 × 10 -6 ) and SOHLH2 (3.48 years earlier menopause, P = 1.03 × 10 -4 ). Collectively, our results suggest that, for the vast majority of women, POI is not caused by autosomal dominant variants either in genes previously reported or currently evaluated in clinical diagnostic panels. Our findings, plus previous studies, suggest that most POI cases are likely oligogenic or polygenic in nature, which has important implications for future clinical genetic studies, and genetic counseling for families affected by POI., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2023
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45. Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Author: Kentistou KA, Kaisinger LR, Stankovic S, Vaudel M, de Oliveira EM, Messina A, Walters RG, Liu X, Busch AS, Helgason H, Thompson DJ, Santon F, Petricek KM, Zouaghi Y, Huang-Doran I, Gudbjartsson DF, Bratland E, Lin K, Gardner EJ, Zhao Y, Jia R, Terao C, Riggan M, Bolla MK, Yazdanpanah M, Yazdanpanah N, Bradfield JP, Broer L, Campbell A, Chasman DI, Cousminer DL, Franceschini N, Franke LH, Girotto G, He C, Järvelin MR, Joshi PK, Kamatani Y, Karlsson R, Luan J, Lunetta KL, Mägi R, Mangino M, Medland SE, Meisinger C, Noordam R, Nutile T, Concas MP, Polašek O, Porcu E, Ring SM, Sala C, Smith AV, Tanaka T, van der Most PJ, Vitart V, Wang CA, Willemsen G, Zygmunt M, Ahearn TU, Andrulis IL, Anton-Culver H, Antoniou AC, Auer PL, Barnes CL, Beckmann MW, Berrington A, Bogdanova NV, Bojesen SE, Brenner H, Buring JE, Canzian F, Chang-Claude J, Couch FJ, Cox A, Crisponi L, Czene K, Daly MB, Demerath EW, Dennis J, Devilee P, Vivo I, Dörk T, Dunning AM, Dwek M, Eriksson JG, Fasching PA, Fernandez-Rhodes L, Ferreli L, Fletcher O, Gago-Dominguez M, García-Closas M, García-Sáenz JA, González-Neira A, Grallert H, Guénel P, Haiman CA, Hall P, Hamann U, Hakonarson H, Hart RJ, Hickey M, Hooning MJ, Hoppe R, Hopper JL, Hottenga JJ, Hu FB, Hübner H, Hunter DJ, Jernström H, John EM, Karasik D, Khusnutdinova EK, Kristensen VN, Lacey JV, Lambrechts D, Launer LJ, Lind PA, Lindblom A, Magnusson PK, Mannermaa A, McCarthy MI, Meitinger T, Menni C, Michailidou K, Millwood IY, Milne RL, Montgomery GW, Nevanlinna H, Nolte IM, Nyholt DR, Obi N, O'Brien KM, Offit K, Oldehinkel AJ, Ostrowski SR, Palotie A, Pedersen OB, Peters A, Pianigiani G, Plaseska-Karanfilska D, Pouta A, Pozarickij A, Radice P, Rennert G, Rosendaal FR, Ruggiero D, Saloustros E, Sandler DP, Schipf S, Schmidt CO, Schmidt MK, Small K, Spedicati B, Stampfer M, Stone J, Tamimi RM, Teras LR, Tikkanen E, Turman C, Vachon CM, Wang Q, Winqvist R, Wolk A, Zemel BS, Zheng W, van Dijk KW, Alizadeh BZ, Bandinelli S, Boerwinkle E, Boomsma DI, Ciullo M, Chenevix-Trench G, Cucca F, Esko T, Gieger C, Grant SF, Gudnason V, Hayward C, Kolčić I, Kraft P, Lawlor DA, Martin NG, Nøhr EA, Pedersen NL, Pennell CE, Ridker PM, Robino A, Snieder H, Sovio U, Spector TD, Stöckl D, Sudlow C, Timpson NJ, Toniolo D, Uitterlinden A, Ulivi S, Völzke H, Wareham NJ, Widen E, Wilson JF, Pharoah PD, Li L, Easton DF, Njølstad P, Sulem P, Murabito JM, Murray A, Manousaki D, Juul A, Erikstrup C, Stefansson K, Horikoshi M, Chen Z, Farooqi IS, Pitteloud N, Johansson S, Day FR, Perry JR, and Ong KK
Abstract: Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively. These common variant analyses were supported by exome sequence analysis of ~220,000 women, identifying several genes, including rare loss of function variants in ZNF483 which abolished the impact of polygenic risk. Next, we implicated 660 genes in pubertal development using a combination of in silico variant-to-gene mapping approaches and integration with dynamic gene expression data from mouse embryonic GnRH neurons. This included an uncharacterized G-protein coupled receptor GPR83 , which we demonstrate amplifies signaling of MC3R , a key sensor of nutritional status. Finally, we identified several genes, including ovary-expressed genes involved in DNA damage response that co-localize with signals associated with menopause timing, leading us to hypothesize that the ovarian reserve might signal centrally to trigger puberty. Collectively these findings extend our understanding of the biological complexity of puberty timing and highlight body size dependent and independent mechanisms that potentially link reproductive timing to later life disease., Competing Interests: Competing interests J.R.B.P. and E.J.G. are employed by Adrestia Therapeutics. D.J.T. is employed by Genomics PLC. D.L.C. and J.P.B. are employed by GSK. E.T. is employed by Pfizer. D.A.L. has received support from Roche Disgnostics and Medtroic Ltd for work unrelated to the research in this paper. T.D.S. is co-founder and stakeholder of Zoe Global Ltd. P.A.F. conducts research funded by Amgen, Novartis and Pfizer, he received Honoraria from Roche, Novartis and Pfizer. M.W.B. conducts research funded by Amgen, Novartis and Pfizer.
Published: 2023
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46. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus.

Author: Mathieson I, Day FR, Barban N, Tropf FC, Brazel DM, Vaez A, van Zuydam N, Bitarello BD, Gardner EJ, Akimova ET, Azad A, Bergmann S, Bielak LF, Boomsma DI, Bosak K, Brumat M, Buring JE, Cesarini D, Chasman DI, Chavarro JE, Cocca M, Concas MP, Davey Smith G, Davies G, Deary IJ, Esko T, Faul JD, Franco O, Ganna A, Gaskins AJ, Gelemanovic A, de Geus EJC, Gieger C, Girotto G, Gopinath B, Grabe HJ, Gunderson EP, Hayward C, He C, van Heemst D, Hill WD, Hoffmann ER, Homuth G, Hottenga JJ, Huang H, Hyppӧnen E, Ikram MA, Jansen R, Johannesson M, Kamali Z, Kardia SLR, Kavousi M, Kifley A, Kiiskinen T, Kraft P, Kühnel B, Langenberg C, Liew G, Lind PA, Luan J, Mägi R, Magnusson PKE, Mahajan A, Martin NG, Mbarek H, McCarthy MI, McMahon G, Medland SE, Meitinger T, Metspalu A, Mihailov E, Milani L, Missmer SA, Mitchell P, Møllegaard S, Mook-Kanamori DO, Morgan A, van der Most PJ, de Mutsert R, Nauck M, Nolte IM, Noordam R, Penninx BWJH, Peters A, Peyser PA, Polašek O, Power C, Pribisalic A, Redmond P, Rich-Edwards JW, Ridker PM, Rietveld CA, Ring SM, Rose LM, Rueedi R, Shukla V, Smith JA, Stankovic S, Stefánsson K, Stöckl D, Strauch K, Swertz MA, Teumer A, Thorleifsson G, Thorsteinsdottir U, Thurik AR, Timpson NJ, Turman C, Uitterlinden AG, Waldenberger M, Wareham NJ, Weir DR, Willemsen G, Zhao JH, Zhao W, Zhao Y, Snieder H, den Hoed M, Ong KK, Mills MC, and Perry JRB
Subjects: Child, Female, Humans, Aging physiology, Menopause genetics, Selection, Genetic, Fertility genetics, Reproduction genetics
Abstract: Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2023
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47. Damaging missense variants in IGF1R implicate a role for IGF-1 resistance in the etiology of type 2 diabetes.

Author: Gardner EJ, Kentistou KA, Stankovic S, Lockhart S, Wheeler E, Day FR, Kerrison ND, Wareham NJ, Langenberg C, O'Rahilly S, Ong KK, and Perry JRB
Abstract: Type 2 diabetes (T2D) is a heritable metabolic disorder. While population studies have identified hundreds of common genetic variants associated with T2D, the role of rare (frequency < 0.1%) protein-coding variation is less clear. We performed exome sequence analysis in 418,436 (n = 32,374 T2D cases) individuals in the UK Biobank. We identified previously reported genes ( GCK , GIGYF1 , HNF1A ) in addition to missense variants in ZEB2 (n = 31 carriers; odds ratio [OR] = 5.5 [95% confidence interval = 2.5-12.0]; p = 6.4 × 10 -7 ), MLXIPL (n = 245; OR = 2.3 [1.6-3.2]; p = 3.2 × 10 -7 ), and IGF1R (n = 394; OR = 2.4 [1.8-3.2]; p = 1.3 × 10 -10 ). Carriers of damaging missense variants within IGF1R were also shorter (-2.2 cm [-1.8 to -2.7]; p = 1.2 × 10 -19 ) and had higher circulating insulin-like growth factor-1 (IGF-1) protein levels (2.3 nmol/L [1.7-2.9]; p = 2.8 × 10 -14 ), indicating relative IGF-1 resistance. A likely causal role of IGF-1 resistance was supported by Mendelian randomization analyses using common variants. These results increase understanding of the genetic architecture of T2D and highlight the growth hormone/IGF-1 axis as a potential therapeutic target., Competing Interests: E.J.G. and J.R.B.P. are employees of and hold shares in Adrestia Therapeutics., (© 2022 The Authors.)
Published: 2022
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48. Detection and characterization of male sex chromosome abnormalities in the UK Biobank study.

Author: Zhao Y, Gardner EJ, Tuke MA, Zhang H, Pietzner M, Koprulu M, Jia RY, Ruth KS, Wood AR, Beaumont RN, Tyrrell J, Jones SE, Lango Allen H, Day FR, Langenberg C, Frayling TM, Weedon MN, Perry JRB, Ong KK, and Murray A
Subjects: Biological Specimen Banks, Humans, Male, Sex Chromosome Aberrations, United Kingdom epidemiology, XYY Karyotype, Diabetes Mellitus, Type 2, Klinefelter Syndrome diagnosis, Klinefelter Syndrome epidemiology, Klinefelter Syndrome genetics
Abstract: Purpose: The study aimed to systematically ascertain male sex chromosome abnormalities, 47,XXY (Klinefelter syndrome [KS]) and 47,XYY, and characterize their risks of adverse health outcomes., Methods: We analyzed genotyping array or exome sequence data in 207,067 men of European ancestry aged 40 to 70 years from the UK Biobank and related these to extensive routine health record data., Results: Only 49 of 213 (23%) of men whom we identified with KS and only 1 of 143 (0.7%) with 47,XYY had a diagnosis of abnormal karyotype on their medical records or self-report. We observed expected associations for KS with reproductive dysfunction (late puberty: risk ratio [RR] = 2.7; childlessness: RR = 4.2; testosterone concentration: RR = -3.8 nmol/L, all P < 2 × 10 -8 ), whereas XYY men appeared to have normal reproductive function. Despite this difference, we identified several higher disease risks shared across both KS and 47,XYY, including type 2 diabetes (RR = 3.0 and 2.6, respectively), venous thrombosis (RR = 6.4 and 7.4, respectively), pulmonary embolism (RR = 3.3 and 3.7, respectively), and chronic obstructive pulmonary disease (RR = 4.4 and 4.6, respectively) (all P < 7 × 10 -6 )., Conclusion: KS and 47,XYY were mostly unrecognized but conferred substantially higher risks for metabolic, vascular, and respiratory diseases, which were only partially explained by higher levels of body mass index, deprivation, and smoking., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2022
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49. Using genetic variation to disentangle the complex relationship between food intake and health outcomes.

Author: Pirastu N, McDonnell C, Grzeszkowiak EJ, Mounier N, Imamura F, Merino J, Day FR, Zheng J, Taba N, Concas MP, Repetto L, Kentistou KA, Robino A, Esko T, Joshi PK, Fischer K, Ong KK, Gaunt TR, Kutalik Z, Perry JRB, and Wilson JF
Subjects: Causality, Humans, Outcome Assessment, Health Care, Risk Factors, Eating, Genetic Variation
Abstract: Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr Joshi is a paid consultant to Global Gene Corp and Humanity Inc.
Published: 2022
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50. Epigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts.

Author: Fraszczyk E, Spijkerman AMW, Zhang Y, Brandmaier S, Day FR, Zhou L, Wackers P, Dollé MET, Bloks VW, Gào X, Gieger C, Kooner J, Kriebel J, Picavet HSJ, Rathmann W, Schöttker B, Loh M, Verschuren WMM, van Vliet-Ostaptchouk JV, Wareham NJ, Chambers JC, Ong KK, Grallert H, Brenner H, Luijten M, and Snieder H
Subjects: CpG Islands genetics, DNA Methylation genetics, Epigenesis, Genetic genetics, Genome-Wide Association Study, Humans, Prospective Studies, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 genetics, Epigenome
Abstract: Aims/hypothesis: Type 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor prevention efforts to those at the highest risk. The aim of this study was to identify predictive methylation markers for incident type 2 diabetes by combining epigenome-wide association study (EWAS) results from five prospective European cohorts., Methods: We conducted a meta-analysis of EWASs in blood collected 7-10 years prior to type 2 diabetes diagnosis. DNA methylation was measured with Illumina Infinium Methylation arrays. A total of 1250 cases and 1950 controls from five longitudinal cohorts were included: Doetinchem, ESTHER, KORA1, KORA2 and EPIC-Norfolk. Associations between DNA methylation and incident type 2 diabetes were examined using robust linear regression with adjustment for potential confounders. Inverse-variance fixed-effects meta-analysis of cohort-level individual CpG EWAS estimates was performed using METAL. The methylGSA R package was used for gene set enrichment analysis. Confirmation of genome-wide significant CpG sites was performed in a cohort of Indian Asians (LOLIPOP, UK)., Results: The meta-analysis identified 76 CpG sites that were differentially methylated in individuals with incident type 2 diabetes compared with control individuals (p values <1.1 × 10 -7 ). Sixty-four out of 76 (84.2%) CpG sites were confirmed by directionally consistent effects and p values <0.05 in an independent cohort of Indian Asians. However, on adjustment for baseline BMI only four CpG sites remained genome-wide significant, and addition of the 76 CpG methylation risk score to a prediction model including established predictors of type 2 diabetes (age, sex, BMI and HbA 1c ) showed no improvement (AUC 0.757 vs 0.753). Gene set enrichment analysis of the full epigenome-wide results clearly showed enrichment of processes linked to insulin signalling, lipid homeostasis and inflammation., Conclusions/interpretation: By combining results from five European cohorts, and thus significantly increasing study sample size, we identified 76 CpG sites associated with incident type 2 diabetes. Replication of 64 CpGs in an independent cohort of Indian Asians suggests that the association between DNA methylation levels and incident type 2 diabetes is robust and independent of ethnicity. Our data also indicate that BMI partly explains the association between DNA methylation and incident type 2 diabetes. Further studies are required to elucidate the underlying biological mechanisms and to determine potential causal roles of the differentially methylated CpG sites in type 2 diabetes development., (© 2022. The Author(s).)
Published: 2022
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