617 results on '"Day, Felix R."'
Search Results
2. Genetic links between ovarian ageing, cancer risk and de novo mutation rates
- Author
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Stankovic, Stasa, Shekari, Saleh, Huang, Qin Qin, Gardner, Eugene J., Ivarsdottir, Erna V., Owens, Nick D. L., Mavaddat, Nasim, Azad, Ajuna, Hawkes, Gareth, Kentistou, Katherine A., Beaumont, Robin N., Day, Felix R., Zhao, Yajie, Jonsson, Hakon, Rafnar, Thorunn, Tragante, Vinicius, Sveinbjornsson, Gardar, Oddsson, Asmundur, Styrkarsdottir, Unnur, Gudmundsson, Julius, Stacey, Simon N., Gudbjartsson, Daniel F., Kennedy, Kitale, Wood, Andrew R., Weedon, Michael N., Ong, Ken K., Wright, Caroline F., Hoffmann, Eva R., Sulem, Patrick, Hurles, Matthew E., Ruth, Katherine S., Martin, Hilary C., Stefansson, Kari, Perry, John R. B., and Murray, Anna
- Published
- 2024
- Full Text
- View/download PDF
3. Understanding the genetic complexity of puberty timing across the allele frequency spectrum
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Kentistou, Katherine A., Kaisinger, Lena R., Stankovic, Stasa, Vaudel, Marc, Mendes de Oliveira, Edson, Messina, Andrea, Walters, Robin G., Liu, Xiaoxi, Busch, Alexander S., Helgason, Hannes, Thompson, Deborah J., Santoni, Federico, Petricek, Konstantin M., Zouaghi, Yassine, Huang-Doran, Isabel, Gudbjartsson, Daniel F., Bratland, Eirik, Lin, Kuang, Gardner, Eugene J., Zhao, Yajie, Jia, Raina Y., Terao, Chikashi, Riggan, Marjorie J., Bolla, Manjeet K., Yazdanpanah, Mojgan, Yazdanpanah, Nahid, Bradfield, Jonathan P., Broer, Linda, Campbell, Archie, Chasman, Daniel I., Cousminer, Diana L., Franceschini, Nora, Franke, Lude H., Girotto, Giorgia, He, Chunyan, Järvelin, Marjo-Riitta, Joshi, Peter K., Kamatani, Yoichiro, Karlsson, Robert, Luan, Jian’an, Lunetta, Kathryn L., Mägi, Reedik, Mangino, Massimo, Medland, Sarah E., Meisinger, Christa, Noordam, Raymond, Nutile, Teresa, Concas, Maria Pina, Polašek, Ozren, Porcu, Eleonora, Ring, Susan M., Sala, Cinzia, Smith, Albert V., Tanaka, Toshiko, van der Most, Peter J., Vitart, Veronique, Wang, Carol A., Willemsen, Gonneke, Zygmunt, Marek, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Auer, Paul L., Barnes, Catriona L. K., Beckmann, Matthias W., Berrington de Gonzalez, Amy, Bogdanova, Natalia V., Bojesen, Stig E., Brenner, Hermann, Buring, Julie E., Canzian, Federico, Chang-Claude, Jenny, Couch, Fergus J., Cox, Angela, Crisponi, Laura, Czene, Kamila, Daly, Mary B., Demerath, Ellen W., Dennis, Joe, Devilee, Peter, De Vivo, Immaculata, Dörk, Thilo, Dunning, Alison M., Dwek, Miriam, Eriksson, Johan G., Fasching, Peter A., Fernandez-Rhodes, Lindsay, Ferreli, Liana, Fletcher, Olivia, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A., González-Neira, Anna, Grallert, Harald, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hakonarson, Hakon, Hart, Roger J., Hickey, Martha, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Hottenga, Jouke-Jan, Hu, Frank B., Huebner, Hanna, Hunter, David J., Jernström, Helena, John, Esther M., Karasik, David, Khusnutdinova, Elza K., Kristensen, Vessela N., Lacey, James V., Lambrechts, Diether, Launer, Lenore J., Lind, Penelope A., Lindblom, Annika, Magnusson, Patrik K. E., Mannermaa, Arto, McCarthy, Mark I., Meitinger, Thomas, Menni, Cristina, Michailidou, Kyriaki, Millwood, Iona Y., Milne, Roger L., Montgomery, Grant W., Nevanlinna, Heli, Nolte, Ilja M., Nyholt, Dale R., Obi, Nadia, O’Brien, Katie M., Offit, Kenneth, Oldehinkel, Albertine J., Ostrowski, Sisse R., Palotie, Aarno, Pedersen, Ole B., Peters, Annette, Pianigiani, Giulia, Plaseska-Karanfilska, Dijana, Pouta, Anneli, Pozarickij, Alfred, Radice, Paolo, Rennert, Gad, Rosendaal, Frits R., Ruggiero, Daniela, Saloustros, Emmanouil, Sandler, Dale P., Schipf, Sabine, Schmidt, Carsten O., Schmidt, Marjanka K., Small, Kerrin, Spedicati, Beatrice, Stampfer, Meir, Stone, Jennifer, Tamimi, Rulla M., Teras, Lauren R., Tikkanen, Emmi, Turman, Constance, Vachon, Celine M., Wang, Qin, Winqvist, Robert, Wolk, Alicja, Zemel, Babette S., Zheng, Wei, van Dijk, Ko W., Alizadeh, Behrooz Z., Bandinelli, Stefania, Boerwinkle, Eric, Boomsma, Dorret I., Ciullo, Marina, Chenevix-Trench, Georgia, Cucca, Francesco, Esko, Tõnu, Gieger, Christian, Grant, Struan F. A., Gudnason, Vilmundur, Hayward, Caroline, Kolčić, Ivana, Kraft, Peter, Lawlor, Deborah A., Martin, Nicholas G., Nøhr, Ellen A., Pedersen, Nancy L., Pennell, Craig E., Ridker, Paul M., Robino, Antonietta, Snieder, Harold, Sovio, Ulla, Spector, Tim D., Stöckl, Doris, Sudlow, Cathie, Timpson, Nic J., Toniolo, Daniela, Uitterlinden, André, Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Widen, Elisabeth, Wilson, James F., Pharoah, Paul D. P., Li, Liming, Easton, Douglas F., Njølstad, Pål R., Sulem, Patrick, Murabito, Joanne M., Murray, Anna, Manousaki, Despoina, Juul, Anders, Erikstrup, Christian, Stefansson, Kari, Horikoshi, Momoko, Chen, Zhengming, Farooqi, I. Sadaf, Pitteloud, Nelly, Johansson, Stefan, Day, Felix R., Perry, John R. B., and Ong, Ken K.
- Published
- 2024
- Full Text
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4. Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry
- Author
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Burns, Kharis, Mullin, Benjamin H., Moolhuijsen, Loes M. E., Laisk, Triin, Tyrmi, Jaakko S., Cui, Jinrui, Actkins, Ky’Era V., Louwers, Yvonne V., Davis, Lea K., Dudbridge, Frank, Azziz, Ricardo, Goodarzi, Mark O., Laivuori, Hannele, Mägi, Reedik, Visser, Jenny A., Laven, Joop S. E., Wilson, Scott G., Day, Felix R., and Stuckey, Bronwyn G. A.
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- 2024
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5. Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease
- Author
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Zhao, Yajie, Chukanova, Maria, Kentistou, Katherine A., Fairhurst-Hunter, Zammy, Siegert, Anna Maria, Jia, Raina Y., Dowsett, Georgina K. C., Gardner, Eugene J., Lawler, Katherine, Day, Felix R., Kaisinger, Lena R., Tung, Yi-Chun Loraine, Lam, Brian Yee Hong, Chen, Hsiao-Jou Cortina, Wang, Quanli, Berumen-Campos, Jaime, Kuri-Morales, Pablo, Tapia-Conyer, Roberto, Alegre-Diaz, Jesus, Barroso, Inês, Emberson, Jonathan, Torres, Jason M., Collins, Rory, Saleheen, Danish, Smith, Katherine R., Paul, Dirk S., Merkle, Florian, Farooqi, I. Sadaf, Wareham, Nick J., Petrovski, Slavé, O’Rahilly, Stephen, Ong, Ken K., Yeo, Giles S. H., and Perry, John R. B.
- Published
- 2024
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6. Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study
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Watts, Eleanor L., Gonzales, Tomas I., Strain, Tessa, Saint-Maurice, Pedro F., Bishop, D. Timothy, Chanock, Stephen J., Johansson, Mattias, Keku, Temitope O., Le Marchand, Loic, Moreno, Victor, Newcomb, Polly A., Newton, Christina C., Pai, Rish K., Purdue, Mark P., Ulrich, Cornelia M., Smith-Byrne, Karl, Van Guelpen, Bethany, Day, Felix R., Wijndaele, Katrien, Wareham, Nicholas J., Matthews, Charles E., Moore, Steven C., and Brage, Soren
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- 2024
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7. Publisher Correction: Understanding the genetic complexity of puberty timing across the allele frequency spectrum
- Author
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Kentistou, Katherine A., Kaisinger, Lena R., Stankovic, Stasa, Vaudel, Marc, Mendes de Oliveira, Edson, Messina, Andrea, Walters, Robin G., Liu, Xiaoxi, Busch, Alexander S., Helgason, Hannes, Thompson, Deborah J., Santoni, Federico, Petricek, Konstantin M., Zouaghi, Yassine, Huang-Doran, Isabel, Gudbjartsson, Daniel F., Bratland, Eirik, Lin, Kuang, Gardner, Eugene J., Zhao, Yajie, Jia, Raina Y., Terao, Chikashi, Riggan, Marjorie J., Bolla, Manjeet K., Yazdanpanah, Mojgan, Yazdanpanah, Nahid, Bradfield, Jonathan P., Broer, Linda, Campbell, Archie, Chasman, Daniel I., Cousminer, Diana L., Franceschini, Nora, Franke, Lude H., Girotto, Giorgia, He, Chunyan, Järvelin, Marjo-Riitta, Joshi, Peter K., Kamatani, Yoichiro, Karlsson, Robert, Luan, Jian’an, Lunetta, Kathryn L., Mägi, Reedik, Mangino, Massimo, Medland, Sarah E., Meisinger, Christa, Noordam, Raymond, Nutile, Teresa, Concas, Maria Pina, Polašek, Ozren, Porcu, Eleonora, Ring, Susan M., Sala, Cinzia, Smith, Albert V., Tanaka, Toshiko, van der Most, Peter J., Vitart, Veronique, Wang, Carol A., Willemsen, Gonneke, Zygmunt, Marek, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Auer, Paul L., Barnes, Catriona L. K., Beckmann, Matthias W., Berrington de Gonzalez, Amy, Bogdanova, Natalia V., Bojesen, Stig E., Brenner, Hermann, Buring, Julie E., Canzian, Federico, Chang-Claude, Jenny, Couch, Fergus J., Cox, Angela, Crisponi, Laura, Czene, Kamila, Daly, Mary B., Demerath, Ellen W., Dennis, Joe, Devilee, Peter, De Vivo, Immaculata, Dörk, Thilo, Dunning, Alison M., Dwek, Miriam, Eriksson, Johan G., Fasching, Peter A., Fernandez-Rhodes, Lindsay, Ferreli, Liana, Fletcher, Olivia, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A., González-Neira, Anna, Grallert, Harald, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hakonarson, Hakon, Hart, Roger J., Hickey, Martha, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Hottenga, Jouke-Jan, Hu, Frank B., Huebner, Hanna, Hunter, David J., Jernström, Helena, John, Esther M., Karasik, David, Khusnutdinova, Elza K., Kristensen, Vessela N., Lacey, James V., Lambrechts, Diether, Launer, Lenore J., Lind, Penelope A., Lindblom, Annika, Magnusson, Patrik K. E., Mannermaa, Arto, McCarthy, Mark I., Meitinger, Thomas, Menni, Cristina, Michailidou, Kyriaki, Millwood, Iona Y., Milne, Roger L., Montgomery, Grant W., Nevanlinna, Heli, Nolte, Ilja M., Nyholt, Dale R., Obi, Nadia, O’Brien, Katie M., Offit, Kenneth, Oldehinkel, Albertine J., Ostrowski, Sisse R., Palotie, Aarno, Pedersen, Ole B., Peters, Annette, Pianigiani, Giulia, Plaseska-Karanfilska, Dijana, Pouta, Anneli, Pozarickij, Alfred, Radice, Paolo, Rennert, Gad, Rosendaal, Frits R., Ruggiero, Daniela, Saloustros, Emmanouil, Sandler, Dale P., Schipf, Sabine, Schmidt, Carsten O., Schmidt, Marjanka K., Small, Kerrin, Spedicati, Beatrice, Stampfer, Meir, Stone, Jennifer, Tamimi, Rulla M., Teras, Lauren R., Tikkanen, Emmi, Turman, Constance, Vachon, Celine M., Wang, Qin, Winqvist, Robert, Wolk, Alicja, Zemel, Babette S., Zheng, Wei, van Dijk, Ko W., Alizadeh, Behrooz Z., Bandinelli, Stefania, Boerwinkle, Eric, Boomsma, Dorret I., Ciullo, Marina, Chenevix-Trench, Georgia, Cucca, Francesco, Esko, Tõnu, Gieger, Christian, Grant, Struan F. A., Gudnason, Vilmundur, Hayward, Caroline, Kolčić, Ivana, Kraft, Peter, Lawlor, Deborah A., Martin, Nicholas G., Nøhr, Ellen A., Pedersen, Nancy L., Pennell, Craig E., Ridker, Paul M., Robino, Antonietta, Snieder, Harold, Sovio, Ulla, Spector, Tim D., Stöckl, Doris, Sudlow, Cathie, Timpson, Nic J., Toniolo, Daniela, Uitterlinden, André, Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Widen, Elisabeth, Wilson, James F., Pharoah, Paul D. P., Li, Liming, Easton, Douglas F., Njølstad, Pål R., Sulem, Patrick, Murabito, Joanne M., Murray, Anna, Manousaki, Despoina, Juul, Anders, Erikstrup, Christian, Stefansson, Kari, Horikoshi, Momoko, Chen, Zhengming, Farooqi, I. Sadaf, Pitteloud, Nelly, Johansson, Stefan, Day, Felix R., Perry, John R. B., and Ong, Ken K.
- Published
- 2024
- Full Text
- View/download PDF
8. Associations of appetitive traits with growth velocities from infancy to childhood
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Olwi, Duaa Ibrahim, Day, Felix R., Cheng, Tuck Seng, Olga, Laurentya, Petry, Clive J., Hughes, Ieuan A., Smith, Andrea D., and Ong, Ken K.
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- 2023
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9. Causal associations between cardiorespiratory fitness and type 2 diabetes
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Cai, Lina, Gonzales, Tomas, Wheeler, Eleanor, Kerrison, Nicola D., Day, Felix R., Langenberg, Claudia, Perry, John R. B., Brage, Soren, and Wareham, Nicholas J.
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- 2023
- Full Text
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10. Penetrance of pathogenic genetic variants associated with premature ovarian insufficiency
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Shekari, Saleh, Stankovic, Stasa, Gardner, Eugene J., Hawkes, Gareth, Kentistou, Katherine A., Beaumont, Robin N., Mörseburg, Alexander, Wood, Andrew R., Prague, Julia K., Mishra, Gita D., Day, Felix R., Baptista, Julia, Wright, Caroline F., Weedon, Michael N., Hoffmann, Eva R., Ruth, Katherine S., Ong, Ken K., Perry, John R. B., and Murray, Anna
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- 2023
- Full Text
- View/download PDF
11. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus
- Author
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Mathieson, Iain, Day, Felix R., Barban, Nicola, Tropf, Felix C., Brazel, David M., Vaez, Ahmad, van Zuydam, Natalie, Bitarello, Bárbara D., Gardner, Eugene J., Akimova, Evelina T., Azad, Ajuna, Bergmann, Sven, Bielak, Lawrence F., Boomsma, Dorret I., Bosak, Kristina, Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey Smith, George, Davies, Gail, Deary, Ian J., Esko, Tõnu, Faul, Jessica D., Franco, Oscar, Ganna, Andrea, Gaskins, Audrey J., Gelemanovic, Andrea, de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Gopinath, Bamini, Grabe, Hans Jörgen, Gunderson, Erica P., Hayward, Caroline, He, Chunyan, van Heemst, Diana, Hill, W. David, Hoffmann, Eva R., Homuth, Georg, Hottenga, Jouke Jan, Huang, Hongyang, Hyppӧnen, Elina, Ikram, M. Arfan, Jansen, Rick, Johannesson, Magnus, Kamali, Zoha, Kardia, Sharon L. R., Kavousi, Maryam, Kifley, Annette, Kiiskinen, Tuomo, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Liew, Gerald, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Milani, Lili, Missmer, Stacey A., Mitchell, Paul, Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nauck, Matthias, Nolte, Ilja M., Noordam, Raymond, Penninx, Brenda W. J. H., Peters, Annette, Peyser, Patricia A., Polašek, Ozren, Power, Chris, Pribisalic, Ajka, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Shukla, Vallari, Smith, Jennifer A., Stankovic, Stasa, Stefánsson, Kári, Stöckl, Doris, Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Uitterlinden, André G., Waldenberger, Melanie, Wareham, Nicholas J., Weir, David R., Willemsen, Gonneke, Zhao, Jing Hau, Zhao, Wei, Zhao, Yajie, Snieder, Harold, den Hoed, Marcel, Ong, Ken K., Mills, Melinda C., and Perry, John R. B.
- Published
- 2023
- Full Text
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12. Genetic insights into biological mechanisms governing human ovarian ageing
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Ruth, Katherine S, Day, Felix R, Hussain, Jazib, Martínez-Marchal, Ana, Aiken, Catherine E, Azad, Ajuna, Thompson, Deborah J, Knoblochova, Lucie, Abe, Hironori, Tarry-Adkins, Jane L, Gonzalez, Javier Martin, Fontanillas, Pierre, Claringbould, Annique, Bakker, Olivier B, Sulem, Patrick, Walters, Robin G, Terao, Chikashi, Turon, Sandra, Horikoshi, Momoko, Lin, Kuang, Onland-Moret, N Charlotte, Sankar, Aditya, Hertz, Emil Peter Thrane, Timshel, Pascal N, Shukla, Vallari, Borup, Rehannah, Olsen, Kristina W, Aguilera, Paula, Ferrer-Roda, Mònica, Huang, Yan, Stankovic, Stasa, Timmers, Paul RHJ, Ahearn, Thomas U, Alizadeh, Behrooz Z, Naderi, Elnaz, Andrulis, Irene L, Arnold, Alice M, Aronson, Kristan J, Augustinsson, Annelie, Bandinelli, Stefania, Barbieri, Caterina M, Beaumont, Robin N, Becher, Heiko, Beckmann, Matthias W, Benonisdottir, Stefania, Bergmann, Sven, Bochud, Murielle, Boerwinkle, Eric, Bojesen, Stig E, Bolla, Manjeet K, Boomsma, Dorret I, Bowker, Nicholas, Brody, Jennifer A, Broer, Linda, Buring, Julie E, Campbell, Archie, Campbell, Harry, Castelao, Jose E, Catamo, Eulalia, Chanock, Stephen J, Chenevix-Trench, Georgia, Ciullo, Marina, Corre, Tanguy, Couch, Fergus J, Cox, Angela, Crisponi, Laura, Cross, Simon S, Cucca, Francesco, Czene, Kamila, Smith, George Davey, de Geus, Eco JCN, de Mutsert, Renée, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Dunning, Alison M, Dwek, Miriam, Eriksson, Mikael, Esko, Tõnu, Fasching, Peter A, Faul, Jessica D, Ferrucci, Luigi, Franceschini, Nora, Frayling, Timothy M, Gago-Dominguez, Manuela, Mezzavilla, Massimo, García-Closas, Montserrat, Gieger, Christian, Giles, Graham G, Grallert, Harald, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Guénel, Pascal, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hayward, Caroline, He, Chunyan, He, Wei, and Heiss, Gerardo
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Estrogen ,Prevention ,Women's Health ,Contraception/Reproduction ,Aging ,Infertility ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Good Health and Well Being ,Adult ,Alleles ,Animals ,Bone and Bones ,Checkpoint Kinase 1 ,Checkpoint Kinase 2 ,Diabetes Mellitus ,Type 2 ,Diet ,Europe ,Asia ,Eastern ,Female ,Fertility ,Fragile X Mental Retardation Protein ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Healthy Aging ,Humans ,Longevity ,Menopause ,Menopause ,Premature ,Mice ,Mice ,Inbred C57BL ,Middle Aged ,Ovary ,Primary Ovarian Insufficiency ,Uterus ,Biobank-based Integrative Omics Study (BIOS) Consortium ,eQTLGen Consortium ,Biobank Japan Project ,China Kadoorie Biobank Collaborative Group ,kConFab Investigators ,LifeLines Cohort Study ,InterAct consortium ,23andMe Research Team ,General Science & Technology - 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
13. Large-scale exome sequence analysis identifies sex- and age-specific determinants of obesity
- Author
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Kaisinger, Lena R., Kentistou, Katherine A., Stankovic, Stasa, Gardner, Eugene J., Day, Felix R., Zhao, Yajie, Mörseburg, Alexander, Carnie, Christopher J., Zagnoli-Vieira, Guido, Puddu, Fabio, Jackson, Stephen P., O’Rahilly, Stephen, Farooqi, I. Sadaf, Dearden, Laura, Pantaleão, Lucas C., Ozanne, Susan E., Ong, Ken K., and Perry, John R.B.
- Published
- 2023
- Full Text
- View/download PDF
14. Damaging missense variants in IGF1R implicate a role for IGF-1 resistance in the etiology of type 2 diabetes
- Author
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Gardner, Eugene J., Kentistou, Katherine A., Stankovic, Stasa, Lockhart, Samuel, Wheeler, Eleanor, Day, Felix R., Kerrison, Nicola D., Wareham, Nicholas J., Langenberg, Claudia, O'Rahilly, Stephen, Ong, Ken K., and Perry, John R.B.
- Published
- 2022
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15. Author Correction: GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability
- Author
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Pasman, Joëlle A, Verweij, Karin JH, Gerring, Zachary, Stringer, Sven, Sanchez-Roige, Sandra, Treur, Jorien L, Abdellaoui, Abdel, Nivard, Michel G, Baselmans, Bart ML, Ong, Jue-Sheng, Ip, Hill F, van der Zee, Matthijs D, Bartels, Meike, Day, Felix R, Fontanillas, Pierre, Elson, Sarah L, de Wit, Harriet, Davis, Lea K, MacKillop, James, Derringer, Jaime L, Branje, Susan JT, Hartman, Catharina A, Heath, Andrew C, van Lier, Pol AC, Madden, Pamela AF, Mägi, Reedik, Meeus, Wim, Montgomery, Grant W, Oldehinkel, AJ, Pausova, Zdenka, Ramos-Quiroga, Josep A, Paus, Tomas, Ribases, Marta, Kaprio, Jaakko, Boks, Marco PM, Bell, Jordana T, Spector, Tim D, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, MacGregor, Stuart, Perry, John RB, Palmer, Abraham A, Posthuma, Danielle, Munafò, Marcus R, Gillespie, Nathan A, Derks, Eske M, and Vink, Jacqueline M
- Subjects
Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Drug Abuse (NIDA only) ,Human Genome ,Brain Disorders ,Serious Mental Illness ,Genetics ,Schizophrenia ,Substance Misuse ,Mental Health ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,23andMe Research Team ,Substance Use Disorders Working Group of the Psychiatric Genomics Consortium ,International Cannabis Consortium ,Neurosciences ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.
- Published
- 2019
16. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
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Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Morgen, Camilla S, van Kampen, Antoine HC, van Schaik, Barbera DC, Mentch, Frank D, Langenberg, Claudia, Luan, Jian’an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil VR, Fonvig, Cilius E, and Trier, Caecilie
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Biological Sciences ,Genetics ,Cardiovascular ,Perinatal Period - Conditions Originating in Perinatal Period ,Nutrition ,Prevention ,Preterm ,Low Birth Weight and Health of the Newborn ,Pediatric ,Obesity ,Conditions Affecting the Embryonic and Fetal Periods ,Infant Mortality ,2.1 Biological and endogenous factors ,Aetiology ,Reproductive health and childbirth ,Good Health and Well Being ,Adult ,Birth Weight ,Blood Pressure ,Body Height ,Diabetes Mellitus ,Type 2 ,Female ,Fetal Development ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Heart Diseases ,Humans ,Infant ,Newborn ,Male ,Maternal Inheritance ,Maternal-Fetal Exchange ,Metabolic Diseases ,Models ,Genetic ,Polymorphism ,Single Nucleotide ,Pregnancy ,Risk Factors ,EGG Consortium ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
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- 2019
17. Epigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts
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Fraszczyk, Eliza, Spijkerman, Annemieke M. W., Zhang, Yan, Brandmaier, Stefan, Day, Felix R., Zhou, Li, Wackers, Paul, Dollé, Martijn E. T., Bloks, Vincent W., Gào, Xīn, Gieger, Christian, Kooner, Jaspal, Kriebel, Jennifer, Picavet, H. Susan J., Rathmann, Wolfgang, Schöttker, Ben, Loh, Marie, Verschuren, W. M. Monique, van Vliet-Ostaptchouk, Jana V., Wareham, Nicholas J., Chambers, John C., Ong, Ken K., Grallert, Harald, Brenner, Hermann, Luijten, Mirjam, and Snieder, Harold
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- 2022
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18. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
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Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Pers, Tune H., Snieder, Harold, Perry, John R. B., Ong, Ken K., den Hoed, Marcel, Barban, Nicola, and Day, Felix R.
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- 2021
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19. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability
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Pasman, Joëlle A, Verweij, Karin JH, Gerring, Zachary, Stringer, Sven, Sanchez-Roige, Sandra, Treur, Jorien L, Abdellaoui, Abdel, Nivard, Michel G, Baselmans, Bart ML, Ong, Jue-Sheng, Ip, Hill F, van der Zee, Matthijs D, Bartels, Meike, Day, Felix R, Fontanillas, Pierre, Elson, Sarah L, the 23andMe Research Team, de Wit, Harriet, Davis, Lea K, MacKillop, James, The Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer, Jaime L, Branje, Susan JT, Hartman, Catharina A, Heath, Andrew C, van Lier, Pol AC, Madden, Pamela AF, Mägi, Reedik, Meeus, Wim, Montgomery, Grant W, Oldehinkel, AJ, Pausova, Zdenka, Ramos-Quiroga, Josep A, Paus, Tomas, Ribases, Marta, Kaprio, Jaakko, Boks, Marco PM, Bell, Jordana T, Spector, Tim D, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, MacGregor, Stuart, Perry, John RB, Palmer, Abraham A, Posthuma, Danielle, Munafò, Marcus R, Gillespie, Nathan A, Derks, Eske M, and Vink, Jacqueline M
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Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Prevention ,Mental Health ,Schizophrenia ,Clinical Research ,Behavioral and Social Science ,Genetics ,Mental Illness ,Brain Disorders ,Serious Mental Illness ,Human Genome ,Drug Abuse (NIDA only) ,Women's Health ,Cannabinoid Research ,Substance Misuse ,2.1 Biological and endogenous factors ,Mental health ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Cell Adhesion Molecules ,Databases ,Genetic ,Female ,Gene Expression Regulation ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Marijuana Abuse ,Mendelian Randomization Analysis ,Middle Aged ,Polymorphism ,Single Nucleotide ,Risk-Taking ,Young Adult ,23andMe Research Team ,Substance Use Disorders Working Group of the Psychiatric Genomics Consortium ,International Cannabis Consortium ,Neurosciences ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.
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- 2018
20. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.
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Pasman, Joëlle A, Verweij, Karin JH, Gerring, Zachary, Stringer, Sven, Sanchez-Roige, Sandra, Treur, Jorien L, Abdellaoui, Abdel, Nivard, Michel G, Baselmans, Bart ML, Ong, Jue-Sheng, Ip, Hill F, van der Zee, Matthijs D, Bartels, Meike, Day, Felix R, Fontanillas, Pierre, Elson, Sarah L, 23andMe Research Team, de Wit, Harriet, Davis, Lea K, MacKillop, James, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer, Jaime L, Branje, Susan JT, Hartman, Catharina A, Heath, Andrew C, van Lier, Pol AC, Madden, Pamela AF, Mägi, Reedik, Meeus, Wim, Montgomery, Grant W, Oldehinkel, AJ, Pausova, Zdenka, Ramos-Quiroga, Josep A, Paus, Tomas, Ribases, Marta, Kaprio, Jaakko, Boks, Marco PM, Bell, Jordana T, Spector, Tim D, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, MacGregor, Stuart, Perry, John RB, Palmer, Abraham A, Posthuma, Danielle, Munafò, Marcus R, Gillespie, Nathan A, Derks, Eske M, and Vink, Jacqueline M
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23andMe Research Team ,Substance Use Disorders Working Group of the Psychiatric Genomics Consortium ,International Cannabis Consortium ,Humans ,Marijuana Abuse ,Genetic Predisposition to Disease ,Cell Adhesion Molecules ,Risk-Taking ,Mental Health ,Schizophrenia ,Gene Expression Regulation ,Genotype ,Polymorphism ,Single Nucleotide ,Databases ,Genetic ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Genome-Wide Association Study ,Young Adult ,Mendelian Randomization Analysis ,Polymorphism ,Single Nucleotide ,Databases ,Genetic ,and over ,Prevention ,Human Genome ,Brain Disorders ,Drug Abuse ,Substance Abuse ,Genetics ,Clinical Research ,2.1 Biological and endogenous factors ,Cardiovascular ,Neurology & Neurosurgery ,Neurosciences ,Cognitive Sciences ,Psychology - Abstract
Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.
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- 2018
21. GWAS of epigenetic aging rates in blood reveals a critical role for TERT.
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Lu, Ake T, Xue, Luting, Salfati, Elias L, Chen, Brian H, Ferrucci, Luigi, Levy, Daniel, Joehanes, Roby, Murabito, Joanne M, Kiel, Douglas P, Tsai, Pei-Chien, Yet, Idil, Bell, Jordana T, Mangino, Massimo, Tanaka, Toshiko, McRae, Allan F, Marioni, Riccardo E, Visscher, Peter M, Wray, Naomi R, Deary, Ian J, Levine, Morgan E, Quach, Austin, Assimes, Themistocles, Tsao, Philip S, Absher, Devin, Stewart, James D, Li, Yun, Reiner, Alex P, Hou, Lifang, Baccarelli, Andrea A, Whitsel, Eric A, Aviv, Abraham, Cardona, Alexia, Day, Felix R, Wareham, Nicholas J, Perry, John RB, Ong, Ken K, Raj, Kenneth, Lunetta, Kathryn L, and Horvath, Steve
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Leukocytes ,Cells ,Cultured ,Telomere ,Fibroblasts ,Humans ,Telomerase ,DNA Methylation ,Epigenesis ,Genetic ,CpG Islands ,Aging ,Menopause ,Menarche ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Child ,Female ,Male ,Genome-Wide Association Study ,Young Adult ,Mendelian Randomization Analysis ,Cells ,Cultured ,Epigenesis ,Genetic ,and over - Abstract
DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA. Variants associated with longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase gene (TERT) paradoxically confer higher IEAA (P
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- 2018
22. Positive maternal attitudes to following healthy infant feeding guidelines attenuate the associations between infant appetitive traits and both infant milk intake and weight
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Clifton, Emma A.D., Ahern, Amy L., Day, Felix R., Sharp, Stephen J., Griffin, Simon J., Ong, Ken K., and Rajalakshmi Lakshman
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- 2021
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23. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.
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Willems, Sara M, Wright, Daniel J, Day, Felix R, Trajanoska, Katerina, Joshi, Peter K, Morris, John A, Matteini, Amy M, Garton, Fleur C, Grarup, Niels, Oskolkov, Nikolay, Thalamuthu, Anbupalam, Mangino, Massimo, Liu, Jun, Demirkan, Ayse, Lek, Monkol, Xu, Liwen, Wang, Guan, Oldmeadow, Christopher, Gaulton, Kyle J, Lotta, Luca A, Miyamoto-Mikami, Eri, Rivas, Manuel A, White, Tom, Loh, Po-Ru, Aadahl, Mette, Amin, Najaf, Attia, John R, Austin, Krista, Benyamin, Beben, Brage, Søren, Cheng, Yu-Ching, Cięszczyk, Paweł, Derave, Wim, Eriksson, Karl-Fredrik, Eynon, Nir, Linneberg, Allan, Lucia, Alejandro, Massidda, Myosotis, Mitchell, Braxton D, Miyachi, Motohiko, Murakami, Haruka, Padmanabhan, Sandosh, Pandey, Ashutosh, Papadimitriou, Ioannis, Rajpal, Deepak K, Sale, Craig, Schnurr, Theresia M, Sessa, Francesco, Shrine, Nick, Tobin, Martin D, Varley, Ian, Wain, Louise V, Wray, Naomi R, Lindgren, Cecilia M, MacArthur, Daniel G, Waterworth, Dawn M, McCarthy, Mark I, Pedersen, Oluf, Khaw, Kay-Tee, Kiel, Douglas P, GEFOS Any-Type of Fracture Consortium, Pitsiladis, Yannis, Fuku, Noriyuki, Franks, Paul W, North, Kathryn N, van Duijn, Cornelia M, Mather, Karen A, Hansen, Torben, Hansson, Ola, Spector, Tim, Murabito, Joanne M, Richards, J Brent, Rivadeneira, Fernando, Langenberg, Claudia, Perry, John RB, Wareham, Nick J, and Scott, Robert A
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GEFOS Any-Type of Fracture Consortium ,Hand ,Humans ,Actins ,Transforming Growth Factor alpha ,Membrane Proteins ,Neoplasm Proteins ,Nuclear Proteins ,Repressor Proteins ,Hand Strength ,Cohort Studies ,Genetics ,Population ,Polymorphism ,Single Nucleotide ,Adult ,Aged ,Middle Aged ,European Continental Ancestry Group ,Female ,Male ,Genome-Wide Association Study ,Genetic Loci ,United Kingdom ,Prevention ,Genetics ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Musculoskeletal - 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
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- 2017
24. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.
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Day, Felix R, Thompson, Deborah J, Helgason, Hannes, Chasman, Daniel I, Finucane, Hilary, Sulem, Patrick, Ruth, Katherine S, Whalen, Sean, Sarkar, Abhishek K, Albrecht, Eva, Altmaier, Elisabeth, Amini, Marzyeh, Barbieri, Caterina M, Boutin, Thibaud, Campbell, Archie, Demerath, Ellen, Giri, Ayush, He, Chunyan, Hottenga, Jouke J, Karlsson, Robert, Kolcic, Ivana, Loh, Po-Ru, Lunetta, Kathryn L, Mangino, Massimo, Marco, Brumat, McMahon, George, Medland, Sarah E, Nolte, Ilja M, Noordam, Raymond, Nutile, Teresa, Paternoster, Lavinia, Perjakova, Natalia, Porcu, Eleonora, Rose, Lynda M, Schraut, Katharina E, Segrè, Ayellet V, Smith, Albert V, Stolk, Lisette, Teumer, Alexander, Andrulis, Irene L, Bandinelli, Stefania, Beckmann, Matthias W, Benitez, Javier, Bergmann, Sven, Bochud, Murielle, Boerwinkle, Eric, Bojesen, Stig E, Bolla, Manjeet K, Brand, Judith S, Brauch, Hiltrud, Brenner, Hermann, Broer, Linda, Brüning, Thomas, Buring, Julie E, Campbell, Harry, Catamo, Eulalia, Chanock, Stephen, Chenevix-Trench, Georgia, Corre, Tanguy, Couch, Fergus J, Cousminer, Diana L, Cox, Angela, Crisponi, Laura, Czene, Kamila, Davey Smith, George, de Geus, Eco JCN, de Mutsert, Renée, De Vivo, Immaculata, Dennis, Joe, Devilee, Peter, Dos-Santos-Silva, Isabel, Dunning, Alison M, Eriksson, Johan G, Fasching, Peter A, Fernández-Rhodes, Lindsay, Ferrucci, Luigi, Flesch-Janys, Dieter, Franke, Lude, Gabrielson, Marike, Gandin, Ilaria, Giles, Graham G, Grallert, Harald, Gudbjartsson, Daniel F, Guénel, Pascal, Hall, Per, Hallberg, Emily, Hamann, Ute, Harris, Tamara B, Hartman, Catharina A, Heiss, Gerardo, Hooning, Maartje J, Hopper, John L, Hu, Frank, Hunter, David J, Ikram, M Arfan, Im, Hae Kyung, Järvelin, Marjo-Riitta, Joshi, Peter K, Karasik, David, and Kellis, Manolis
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LifeLines Cohort Study ,InterAct Consortium ,kConFab/AOCS Investigators ,Endometrial Cancer Association Consortium ,Ovarian Cancer Association Consortium ,PRACTICAL consortium ,Humans ,Neoplasms ,Genetic Predisposition to Disease ,Ubiquitin-Protein Ligases ,Intercellular Signaling Peptides and Proteins ,Calcium-Binding Proteins ,Ribonucleoproteins ,Membrane Proteins ,Body Mass Index ,Risk Factors ,Age Factors ,Genomic Imprinting ,Puberty ,Menarche ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Databases ,Genetic ,Adolescent ,Female ,Male ,Genome-Wide Association Study ,Aging ,Breast Cancer ,Biotechnology ,Cancer ,Human Genome ,Genetics ,Prostate Cancer ,Urologic Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - 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.
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- 2017
25. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance
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Lotta, Luca A, Gulati, Pawan, Day, Felix R, Payne, Felicity, Ongen, Halit, van de Bunt, Martijn, Gaulton, Kyle J, Eicher, John D, Sharp, Stephen J, Luan, Jian'an, De Lucia Rolfe, Emanuella, Stewart, Isobel D, Wheeler, Eleanor, Willems, Sara M, Adams, Claire, Yaghootkar, Hanieh, Forouhi, Nita G, Khaw, Kay-Tee, Johnson, Andrew D, Semple, Robert K, Frayling, Timothy, Perry, John RB, Dermitzakis, Emmanouil, McCarthy, Mark I, Barroso, Inês, Wareham, Nicholas J, Savage, David B, Langenberg, Claudia, O'Rahilly, Stephen, and Scott, Robert A
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Biochemistry and Cell Biology ,Biological Sciences ,Clinical Research ,Human Genome ,Genetics ,Diabetes ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Adipose Tissue ,Animals ,Blood Glucose ,Body Mass Index ,Cardiovascular Diseases ,Case-Control Studies ,Disease Models ,Animal ,Female ,Genome-Wide Association Study ,Genomics ,Humans ,Insulin Resistance ,Male ,Metabolic Diseases ,Mice ,Obesity ,Phenotype ,EPIC-InterAct Consortium ,Cambridge FPLD1 Consortium ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.
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- 2017
26. Observational and genetic associations between cardiorespiratory fitness and cancer:a UK Biobank and international consortia study
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Watts, Eleanor L., Gonzales, Tomas I., Strain, Tessa, Saint-Maurice, Pedro F., Bishop, D. Timothy, Chanock, Stephen J., Johansson, Mattias, Keku, Temitope O., Le Marchand, Loic, Moreno, Victor, Newcomb, Polly A., Newton, Christina C., Pai, Rish K., Purdue, Mark P., Ulrich, Cornelia M., Smith-Byrne, Karl, Van Guelpen, Bethany, Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Wang, Ying, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M.L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Day, Felix R., Wijndaele, Katrien, Wareham, Nicholas J., Matthews, Charles E., Moore, Steven C., Brage, Soren, Watts, Eleanor L., Gonzales, Tomas I., Strain, Tessa, Saint-Maurice, Pedro F., Bishop, D. Timothy, Chanock, Stephen J., Johansson, Mattias, Keku, Temitope O., Le Marchand, Loic, Moreno, Victor, Newcomb, Polly A., Newton, Christina C., Pai, Rish K., Purdue, Mark P., Ulrich, Cornelia M., Smith-Byrne, Karl, Van Guelpen, Bethany, Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Wang, Ying, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M.L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Day, Felix R., Wijndaele, Katrien, Wareham, Nicholas J., Matthews, Charles E., Moore, Steven C., and Brage, Soren
- 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 O2⋅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 O2⋅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.
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- 2024
27. Genetic analyses identify widespread sex-differential participation bias
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Pirastu, Nicola, Cordioli, Mattia, Nandakumar, Priyanka, Mignogna, Gianmarco, Abdellaoui, Abdel, Hollis, Benjamin, Kanai, Masahiro, Rajagopal, Veera M., Parolo, Pietro Della Briotta, Baya, Nikolas, Carey, Caitlin E., Karjalainen, Juha, Als, Thomas D., Van der Zee, Matthijs D., Day, Felix R., Ong, Ken K., Morisaki, Takayuki, de Geus, Eco, Bellocco, Rino, Okada, Yukinori, Børglum, Anders D., Joshi, Peter, Auton, Adam, Hinds, David, Neale, Benjamin M., Walters, Raymond K., Nivard, Michel G., Perry, John R. B., and Ganna, Andrea
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- 2021
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28. Penetrance of Pathogenic Genetic Variants Associated With Premature Ovarian Insufficiency
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Shekari, Saleh, primary, Stankovic, Stasa, additional, Gardner, Eugene J., additional, Hawkes, Gareth, additional, Kentistou, Katherine A., additional, Beaumont, Robin N., additional, Mörseburg, Alexander, additional, Wood, Andrew R., additional, Prague, Julia K., additional, Mishra, Gita D., additional, Day, Felix R., additional, Baptista, Julia, additional, Wright, Caroline F., additional, Weedon, Michael N., additional, Hoffmann, Eva R., additional, Ruth, Katherine S., additional, Ong, Ken K., additional, Perry, John R. B., additional, and Murray, Anna, additional
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- 2024
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29. Genome-wide associations for birth weight and correlations with adult disease
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Horikoshi, Momoko, Beaumont, Robin N, Day, Felix R, Warrington, Nicole M, Kooijman, Marjolein N, Fernandez-Tajes, Juan, Feenstra, Bjarke, van Zuydam, Natalie R, Gaulton, Kyle J, Grarup, Niels, Bradfield, Jonathan P, Strachan, David P, Li-Gao, Ruifang, Ahluwalia, Tarunveer S, Kreiner, Eskil, Rueedi, Rico, Lyytikäinen, Leo-Pekka, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Hottenga, Jouke-Jan, Vilor-Tejedor, Natalia, Joshi, Peter K, Boh, Eileen Tai Hui, Ntalla, Ioanna, Pitkänen, Niina, Mahajan, Anubha, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Nodzenski, Michael, Diver, Louise A, Zondervan, Krina T, Bustamante, Mariona, Marques-Vidal, Pedro, Mercader, Josep M, Bennett, Amanda J, Rahmioglu, Nilufer, Nyholt, Dale R, Ma, Ronald CW, Tam, Claudia HT, Tam, Wing Hung, Ganesh, Santhi K, van Rooij, Frank JA, Jones, Samuel E, Loh, Po-Ru, Ruth, Katherine S, Tuke, Marcus A, Tyrrell, Jessica, Wood, Andrew R, Yaghootkar, Hanieh, Scholtens, Denise M, Paternoster, Lavinia, Prokopenko, Inga, Kovacs, Peter, Atalay, Mustafa, Willems, Sara M, Panoutsopoulou, Kalliope, Wang, Xu, Carstensen, Lisbeth, Geller, Frank, Schraut, Katharina E, Murcia, Mario, van Beijsterveldt, Catharina EM, Willemsen, Gonneke, Appel, Emil VR, Fonvig, Cilius E, Trier, Caecilie, Tiesler, Carla MT, Standl, Marie, Kutalik, Zoltán, Bonàs-Guarch, Sílvia, Hougaard, David M, Sánchez, Friman, Torrents, David, Waage, Johannes, Hollegaard, Mads V, de Haan, Hugoline G, Rosendaal, Frits R, Medina-Gomez, Carolina, Ring, Susan M, Hemani, Gibran, McMahon, George, Robertson, Neil R, Groves, Christopher J, Langenberg, Claudia, Luan, Jian’an, Scott, Robert A, Zhao, Jing Hua, Mentch, Frank D, MacKenzie, Scott M, Reynolds, Rebecca M, Lowe, William L, Tönjes, Anke, Stumvoll, Michael, Lindi, Virpi, Lakka, Timo A, and van Duijn, Cornelia M
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Nutrition ,Perinatal Period - Conditions Originating in Perinatal Period ,Human Genome ,Genetics ,Clinical Research ,Preterm ,Low Birth Weight and Health of the Newborn ,Obesity ,Prevention ,Pediatric ,Infant Mortality ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Aging ,Anthropometry ,Birth Weight ,Blood Pressure ,Chromatin Assembly and Disassembly ,Cohort Studies ,Coronary Artery Disease ,Datasets as Topic ,Diabetes Mellitus ,Type 2 ,Female ,Fetus ,Genetic Loci ,Genetic Predisposition to Disease ,Genetic Variation ,Genome-Wide Association Study ,Genomic Imprinting ,Genotype ,Glucose ,Glycogen ,Humans ,Insulin ,Male ,Phenotype ,Signal Transduction ,CHARGE Consortium Hematology Working Group ,Early Growth Genetics (EGG) Consortium ,General Science & Technology - 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 (P
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- 2016
30. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.
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Kilpeläinen, Tuomas O, Carli, Jayne F Martin, Skowronski, Alicja A, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K, Drong, Alexander W, Hayes, James E, Zhao, Jinghua, Pers, Tune H, Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Del Greco M, Fabiola, Pasko, Dorota, Renström, Frida, Willems, Sara M, Mahajan, Anubha, Rose, Lynda M, Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E, Pérusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S, Ju Sung, Yun, Ramos, Yolande F, Amin, Najaf, Amuzu, Antoinette, Barroso, Inês, Bellis, Claire, Blangero, John, Buckley, Brendan M, Böhringer, Stefan, I Chen, Yii-Der, de Craen, Anton JN, Crosslin, David R, Dale, Caroline E, Dastani, Zari, Day, Felix R, Deelen, Joris, Delgado, Graciela E, Demirkan, Ayse, Finucane, Francis M, Ford, Ian, Garcia, Melissa E, Gieger, Christian, Gustafsson, Stefan, Hallmans, Göran, Hankinson, Susan E, Havulinna, Aki S, Herder, Christian, Hernandez, Dena, Hicks, Andrew A, Hunter, David J, Illig, Thomas, Ingelsson, Erik, Ioan-Facsinay, Andreea, Jansson, John-Olov, Jenny, Nancy S, Jørgensen, Marit E, Jørgensen, Torben, Karlsson, Magnus, Koenig, Wolfgang, Kraft, Peter, Kwekkeboom, Joanneke, Laatikainen, Tiina, Ladwig, Karl-Heinz, LeDuc, Charles A, Lowe, Gordon, Lu, Yingchang, Marques-Vidal, Pedro, Meisinger, Christa, Menni, Cristina, Morris, Andrew P, Myers, Richard H, Männistö, Satu, Nalls, Mike A, Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rathmann, Wolfgang, Rice, Treva K, Brent Richards, J, Ridker, Paul M, Sattar, Naveed, and Savage, David B
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Adipose Tissue ,Animals ,Mice ,Leptin ,RNA ,Messenger ,Tissue Culture Techniques ,Gene Expression Regulation ,Male ,Genome-Wide Association Study ,Gene Knockdown Techniques ,RNA ,Messenger - Abstract
Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P
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- 2016
31. Genetic association study of childhood aggression across raters, instruments, and age
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Ip, Hill F., van der Laan, Camiel M., Krapohl, Eva M. L., Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja M., St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol A., Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke R., Adkins, Daniel E., Border, Richard, Peterson, Roseann E., Prinz, Joseph A., Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer S., Day, Felix R., Hottenga, Jouke-Jan, Allegrini, Andrea G., Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep Antoni, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José J., Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James G., Vinkhuyzen, Anna, Shabalin, Andrey A., Corley, Robin, Evans, Luke M., Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth E., Ehli, Erik A., Hagenbeek, Fiona A., De Zeeuw, Eveline, Van Beijsterveldt, Toos C.E.M., Larsson, Henrik, Snieder, Harold, Verhulst, Frank C., Amin, Najaf, Whipp, Alyce M., Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard J., Uitterlinden, André G., Heath, Andrew C., Madden, Pamela, Haavik, Jan, Harris, Jennifer R., Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun Peggy S., Njolstad, Pal Rasmus, Lu, Qing, Rodriguez, Alina, Henders, Anjali K., Mamun, Abdullah, Najman, Jackob M., Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara L., Silberg, Judy L., Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, Raitakari, Olli T., Perry, John R. B., Llop, Sabrina, Lopez-Espinosa, Maria-Jose, Bønnelykke, Klaus, Bisgaard, Hans, Sunyer, Jordi, Lehtimäki, Terho, Arseneault, Louise, Standl, Marie, Heinrich, Joachim, Boden, Joseph, Pearson, John, Horwood, L. John, Kennedy, Martin, Poulton, Richie, Eaves, Lindon J., Maes, Hermine H., Hewitt, John, Copeland, William E., Costello, Elizabeth J., Williams, Gail M., Wray, Naomi, Järvelin, Marjo-Riitta, McGue, Matt, Iacono, William, Caspi, Avshalom, Moffitt, Terrie E., Whitehouse, Andrew, Pennell, Craig E., Klump, Kelly L., Burt, S. Alexandra, Dick, Danielle M., Reichborn-Kjennerud, Ted, Martin, Nicholas G., Medland, Sarah E., Vrijkotte, Tanja, Kaprio, Jaakko, Tiemeier, Henning, Davey Smith, George, Hartman, Catharina A., Oldehinkel, Albertine J., Casas, Miquel, Ribasés, Marta, Lichtenstein, Paul, Lundström, Sebastian, Plomin, Robert, Bartels, Meike, Nivard, Michel G., and Boomsma, Dorret I.
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- 2021
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32. Using human genetics to understand the disease impacts of testosterone in men and women
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Ruth, Katherine S, Day, Felix R, Tyrrell, Jessica, Thompson, Deborah J, Wood, Andrew R, Mahajan, Anubha, and Beaumont, Robin N
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Genetic variation -- Health aspects -- Demographic aspects ,Testosterone -- Health aspects ,Biological sciences ,Health - Abstract
Testosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Biobank study participants. Using 2,571 genome-wide significant associations, we demonstrate that the genetic determinants of testosterone levels are substantially different between sexes and that genetically higher testosterone is harmful for metabolic diseases in women but beneficial in men. For example, a genetically determined 1 s.d. higher testosterone increases the risks of type 2 diabetes (odds ratio (OR) = 1.37 (95% confidence interval (95% CI): 1.22-1.53)) and polycystic ovary syndrome (OR = 1.51 (95% CI: 1.33-1.72)) in women, but reduces type 2 diabetes risk in men (OR = 0.86 (95% CI: 0.76-0.98)). We also show adverse effects of higher testosterone on breast and endometrial cancers in women and prostate cancer in men. Our findings provide insights into the disease impacts of testosterone and highlight the importance of sex-specific genetic analyses. Genetic analysis of data from over 400,000 participants in the UK Biobank Study shows that circulating testosterone levels have sex-specific implications for cardiometabolic diseases and cancer outcomes., Author(s): Katherine S Ruth [sup.1] , Felix R Day [sup.2] , Jessica Tyrrell [sup.1] , Deborah J Thompson [sup.3] , Andrew R Wood [sup.1] , Anubha Mahajan [sup.4] , Robin [...]
- Published
- 2020
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33. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.
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Day, Felix R, Ruth, Katherine S, Thompson, Deborah J, Lunetta, Kathryn L, Pervjakova, Natalia, Chasman, Daniel I, Stolk, Lisette, Finucane, Hilary K, Sulem, Patrick, Bulik-Sullivan, Brendan, Esko, Tõnu, Johnson, Andrew D, Elks, Cathy E, Franceschini, Nora, He, Chunyan, Altmaier, Elisabeth, Brody, Jennifer A, Franke, Lude L, Huffman, Jennifer E, Keller, Margaux F, McArdle, Patrick F, Nutile, Teresa, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M, Schick, Ursula M, Smith, Jennifer A, Teumer, Alexander, Traglia, Michela, Vuckovic, Dragana, Yao, Jie, Zhao, Wei, Albrecht, Eva, Amin, Najaf, Corre, Tanguy, Hottenga, Jouke-Jan, Mangino, Massimo, Smith, Albert V, Tanaka, Toshiko, Abecasis, Goncalo, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Arndt, Volker, Arnold, Alice M, Barbieri, Caterina, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bernstein, Leslie, Bielinski, Suzette J, Blomqvist, Carl, Boerwinkle, Eric, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Borresen-Dale, Anne-Lise, Boutin, Thibaud S, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Burwinkel, Barbara, Campbell, Archie, Campbell, Harry, Chanock, Stephen J, Chapman, J Ross, Chen, Yii-Der Ida, Chenevix-Trench, Georgia, Couch, Fergus J, Coviello, Andrea D, Cox, Angela, Czene, Kamila, Darabi, Hatef, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dunning, Alison M, Eicher, John D, Fasching, Peter A, Faul, Jessica D, Figueroa, Jonine, Flesch-Janys, Dieter, Gandin, Ilaria, Garcia, Melissa E, García-Closas, Montserrat, Giles, Graham G, Girotto, Giorgia G, Goldberg, Mark S, González-Neira, Anna, Goodarzi, Mark O, Grove, Megan L, Gudbjartsson, Daniel F, Guénel, Pascal, Guo, Xiuqing, Haiman, Christopher A, Hall, Per, and Hamann, Ute
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PRACTICAL consortium ,kConFab Investigators ,AOCS Investigators ,Generation Scotland ,EPIC-InterAct Consortium ,LifeLines Cohort Study ,Hypothalamus ,Humans ,Breast Neoplasms ,Genetic Predisposition to Disease ,BRCA1 Protein ,Genomics ,Age Factors ,Signal Transduction ,DNA Repair ,Aging ,Reproduction ,Menopause ,Genotype ,Phenotype ,Models ,Genetic ,Adult ,Middle Aged ,Female ,Gene Regulatory Networks ,Genetic Variation ,Genome-Wide Association Study ,Models ,Genetic ,Developmental Biology ,Medical and Health Sciences ,Biological Sciences - Abstract
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 ∼70,000 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 (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
- Published
- 2015
34. New genetic loci link adipose and insulin biology to body fat distribution
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Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Locke, Adam E, Mägi, Reedik, Strawbridge, Rona J, Pers, Tune H, Fischer, Krista, Justice, Anne E, Workalemahu, Tsegaselassie, Wu, Joseph MW, Buchkovich, Martin L, Heard-Costa, Nancy L, Roman, Tamara S, Drong, Alexander W, Song, Ci, Gustafsson, Stefan, Day, Felix R, Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jian’an, Randall, Joshua C, Scherag, André, Vedantam, Sailaja, Wood, Andrew R, Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M, Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L, Buyske, Steven, Demirkan, Ayse, Ehret, Georg B, Feitosa, Mary F, Goel, Anuj, Jackson, Anne U, Johnson, Toby, Kleber, Marcus E, Kristiansson, Kati, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J, Prokopenko, Inga, Stančáková, Alena, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V, Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B, Caspersen, Ida H, Clarke, Robert, Warwick Daw, E, Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex SF, Eklund, Niina, Erdos, Michael R, Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S, Golay, Alain, Grallert, Harald, Grammer, Tanja B, Gräßler, Jürgen, Grewal, Jagvir, Groves, Christopher J, Haller, Toomas, and Hallmans, Goran
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Genetics ,Human Genome ,Diabetes ,Obesity ,Nutrition ,2.1 Biological and endogenous factors ,Aetiology ,Metabolic and endocrine ,Cardiovascular ,Stroke ,Adipocytes ,Adipogenesis ,Adipose Tissue ,Age Factors ,Body Fat Distribution ,Body Mass Index ,Epigenesis ,Genetic ,Europe ,Female ,Genome ,Human ,Genome-Wide Association Study ,Humans ,Insulin ,Insulin Resistance ,Male ,Models ,Biological ,Neovascularization ,Physiologic ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Racial Groups ,Sex Characteristics ,Transcription ,Genetic ,Waist-Hip Ratio ,ADIPOGen Consortium ,CARDIOGRAMplusC4D Consortium ,CKDGen Consortium ,GEFOS Consortium ,GENIE Consortium ,GLGC ,ICBP ,International Endogene Consortium ,LifeLines Cohort Study ,MAGIC Investigators ,MuTHER Consortium ,PAGE Consortium ,ReproGen Consortium ,General Science & Technology - Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P
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- 2015
35. Genetic studies of body mass index yield new insights for obesity biology
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Locke, Adam E, Kahali, Bratati, Berndt, Sonja I, Justice, Anne E, Pers, Tune H, Day, Felix R, Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L, Yang, Jian, Croteau-Chonka, Damien C, Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltán, Luan, Jian’an, Mägi, Reedik, Randall, Joshua C, Winkler, Thomas W, Wood, Andrew R, Workalemahu, Tsegaselassie, Faul, Jessica D, Smith, Jennifer A, Hua Zhao, Jing, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Åsa K, Karjalainen, Juha, Schmidt, Ellen M, Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L, Bragg-Gresham, Jennifer L, Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B, Feenstra, Bjarke, Feitosa, Mary F, Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U, Kanoni, Stavroula, Kleber, Marcus E, Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Medland, Sarah E, Nalls, Michael A, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J, Prokopenko, Inga, Shungin, Dmitry, Stančáková, Alena, Strawbridge, Rona J, Ju Sung, Yun, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V, Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M, Attwood, Antony P, Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blagieva, Roza, Blüher, Matthias, Böhringer, Stefan, Bonnycastle, Lori L, Böttcher, Yvonne, Boyd, Heather A, Bruinenberg, Marcel, Caspersen, Ida H, Ida Chen, Yii-Der, Clarke, Robert, Warwick Daw, E, de Craen, Anton JM, Delgado, Graciela, and Dimitriou, Maria
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Nutrition ,Obesity ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Stroke ,Cardiovascular ,Metabolic and endocrine ,Oral and gastrointestinal ,Cancer ,Adipogenesis ,Adiposity ,Age Factors ,Body Mass Index ,Energy Metabolism ,Europe ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Glutamic Acid ,Humans ,Insulin ,Insulin Secretion ,Male ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Racial Groups ,Synapses ,LifeLines Cohort Study ,ADIPOGen Consortium ,AGEN-BMI Working Group ,CARDIOGRAMplusC4D Consortium ,CKDGen Consortium ,GLGC ,ICBP ,MAGIC Investigators ,MuTHER Consortium ,MIGen Consortium ,PAGE Consortium ,ReproGen Consortium ,GENIE Consortium ,International Endogene Consortium ,General Science & Technology - Abstract
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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- 2015
36. Defining the role of common variation in the genomic and biological architecture of adult human height
- Author
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Wood, Andrew R, Esko, Tonu, Yang, Jian, Vedantam, Sailaja, Pers, Tune H, Gustafsson, Stefan, Chu, Audrey Y, Estrada, Karol, Luan, Jian'an, Kutalik, Zoltán, Amin, Najaf, Buchkovich, Martin L, Croteau-Chonka, Damien C, Day, Felix R, Duan, Yanan, Fall, Tove, Fehrmann, Rudolf, Ferreira, Teresa, Jackson, Anne U, Karjalainen, Juha, Lo, Ken Sin, Locke, Adam E, Mägi, Reedik, Mihailov, Evelin, Porcu, Eleonora, Randall, Joshua C, Scherag, André, Vinkhuyzen, Anna AE, Westra, Harm-Jan, Winkler, Thomas W, Workalemahu, Tsegaselassie, Zhao, Jing Hua, Absher, Devin, Albrecht, Eva, Anderson, Denise, Baron, Jeffrey, Beekman, Marian, Demirkan, Ayse, Ehret, Georg B, Feenstra, Bjarke, Feitosa, Mary F, Fischer, Krista, Fraser, Ross M, Goel, Anuj, Gong, Jian, Justice, Anne E, Kanoni, Stavroula, Kleber, Marcus E, Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Lui, Julian C, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Nalls, Michael A, Nyholt, Dale R, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Prokopenko, Inga, Ried, Janina S, Ripke, Stephan, Shungin, Dmitry, Stancáková, Alena, Strawbridge, Rona J, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V, Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Afzal, Uzma, Ärnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Bolton, Jennifer L, Böttcher, Yvonne, Boyd, Heather A, Bruinenberg, Marcel, Buckley, Brendan M, Buyske, Steven, Caspersen, Ida H, Chines, Peter S, Clarke, Robert, Claudi-Boehm, Simone, Cooper, Matthew, Daw, E Warwick, De Jong, Pim A, Deelen, Joris, and Delgado, Graciela
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Biological Sciences ,Genetics ,Biotechnology ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Analysis of Variance ,Body Height ,Genetic Variation ,Genetics ,Population ,Genome-Wide Association Study ,Humans ,Oligonucleotide Array Sequence Analysis ,Polymorphism ,Single Nucleotide ,White People ,Electronic Medical Records and Genomics (eMEMERGEGE) Consortium ,MIGen Consortium ,PAGEGE Consortium ,LifeLines Cohort Study ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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- 2014
37. Genetic Insights Into Biological Mechanisms Governing Human Ovarian Ageing
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Ruth, Katherine S., Day, Felix R., and Hussain, Jazib, et al.
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- 2021
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38. Protein-truncating variants inBSNare associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease
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Zhao, Yajie, primary, Chukanova, Maria, additional, Kentistou, Katherine A, additional, Fairhurst-Hunter, Zammy, additional, Siegert, Anna Maria, additional, Jia, Raina, additional, Dowsett, Georgina, additional, Gardner, Eugene J, additional, Day, Felix R, additional, Kaisinger, Lena R, additional, Tung, Yi-Chun Loraine, additional, Hong Lam, Brian Yee, additional, Chen, Hsiao-Jou Cortina, additional, Wang, Quanli, additional, Berumen-Campos, Jaime, additional, Kuri-Morales, Pablo, additional, Tapia-Conyer, Roberto, additional, Alegre-Diaz, Jesus, additional, Emberson, Jonathan, additional, Torres, Jason M, additional, Collins, Rory, additional, Saleheen, Danish, additional, Smith, Katherine R, additional, Paul, Dirk S, additional, Merkle, Florian, additional, Wareham, Nick J, additional, Petrovski, Slavé, additional, O’Rahilly, Steve, additional, Ong, Ken K, additional, Yeo, Giles S H, additional, and Perry, John R B, additional
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- 2023
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39. Protein-truncating variants in BSNare associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease
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Zhao, Yajie, Chukanova, Maria, Kentistou, Katherine A., Fairhurst-Hunter, Zammy, Siegert, Anna Maria, Jia, Raina Y., Dowsett, Georgina K. C., Gardner, Eugene J., Lawler, Katherine, Day, Felix R., Kaisinger, Lena R., Tung, Yi-Chun Loraine, Lam, Brian Yee Hong, Chen, Hsiao-Jou Cortina, Wang, Quanli, Berumen-Campos, Jaime, Kuri-Morales, Pablo, Tapia-Conyer, Roberto, Alegre-Diaz, Jesus, Barroso, Inês, Emberson, Jonathan, Torres, Jason M., Collins, Rory, Saleheen, Danish, Smith, Katherine R., Paul, Dirk S., Merkle, Florian, Farooqi, I. Sadaf, Wareham, Nick J., Petrovski, Slavé, O’Rahilly, Stephen, Ong, Ken K., Yeo, Giles S. H., and Perry, John R. B.
- 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 (BSNand 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 BSNand APBA1were not associated with normal variation in childhood adiposity. Furthermore, BSNprotein-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 BSNPTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSNPTV carriers as well as the functional consequences of BSNdeletion 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.
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- 2024
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40. Replication and characterization of CADM2 and MSRA genes on human behavior
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Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Hinds, David A., Hromatka, Bethann S., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McIntyre, Matthew H., Mountain, Joanna L., Northover, Carrie A.M., Sathirapongsasuti, J.Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Boutwell, Brian, Hinds, David, Tielbeek, Jorim, Ong, Ken K., Day, Felix R., and Perry, John R.B.
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- 2017
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41. Genetic basis of falling risk susceptibility in the UK Biobank Study
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Trajanoska, Katerina, Seppala, Lotta J., Medina-Gomez, Carolina, Hsu, Yi-Hsiang, Zhou, Sirui, van Schoor, Natasja M., de Groot, Lisette C. P. G. M., Karasik, David, Richards, J. Brent, Kiel, Douglas P., Uitterlinden, Andre G., Perry, John R. B., van der Velde, Nathalie, Day, Felix R., and Rivadeneira, Fernando
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- 2020
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42. The potential shared role of inflammation in insulin resistance and schizophrenia: A bidirectional two-sample mendelian randomization study
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Perry, Benjamin I., Burgess, Stephen, Jones, Hannah J., Zammit, Stan, Upthegrove, Rachel, Mason, Amy M., Day, Felix R., Langenberg, Claudia, Wareham, Nicholas J., Jones, Peter B., and Khandaker, Golam M.
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Inflammation -- Genetic aspects ,Schizophrenia -- Genetic aspects -- Development and progression -- Risk factors ,Insulin resistance -- Genetic aspects -- Development and progression -- Risk factors ,Biological sciences - Abstract
Background Insulin resistance predisposes to cardiometabolic disorders, which are commonly comorbid with schizophrenia and are key contributors to the significant excess mortality in schizophrenia. Mechanisms for the comorbidity remain unclear, but observational studies have implicated inflammation in both schizophrenia and cardiometabolic disorders separately. We aimed to examine whether there is genetic evidence that insulin resistance and 7 related cardiometabolic traits may be causally associated with schizophrenia, and whether evidence supports inflammation as a common mechanism for cardiometabolic disorders and schizophrenia. Methods and findings We used summary data from genome-wide association studies of mostly European adults from large consortia (Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) featuring up to 108,557 participants; Diabetes Genetics Replication And Meta-analysis (DIAGRAM) featuring up to 435,387 participants; Global Lipids Genetics Consortium (GLGC) featuring up to 173,082 participants; Genetic Investigation of Anthropometric Traits (GIANT) featuring up to 339,224 participants; Psychiatric Genomics Consortium (PGC) featuring up to 105,318 participants; and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium featuring up to 204,402 participants). We conducted two-sample uni- and multivariable mendelian randomization (MR) analysis to test whether (i) 10 cardiometabolic traits (fasting insulin, high-density lipoprotein and triglycerides representing an insulin resistance phenotype, and 7 related cardiometabolic traits: low-density lipoprotein, fasting plasma glucose, glycated haemoglobin, leptin, body mass index, glucose tolerance, and type 2 diabetes) could be causally associated with schizophrenia; and (ii) inflammation could be a shared mechanism for these phenotypes. We conducted a detailed set of sensitivity analyses to test the assumptions for a valid MR analysis. We did not find statistically significant evidence in support of a causal relationship between cardiometabolic traits and schizophrenia, or vice versa. However, we report that a genetically predicted inflammation-related insulin resistance phenotype (raised fasting insulin (raised fasting insulin (Wald ratio OR = 2.95, 95% C.I, 1.38-6.34, Holm-Bonferroni corrected p-value (p) = 0.035) and lower high-density lipoprotein (Wald ratio OR = 0.55, 95% C.I., 0.36-0.84; p = 0.035)) was associated with schizophrenia. Evidence for these associations attenuated to the null in multivariable MR analyses after adjusting for C-reactive protein, an archetypal inflammatory marker: (fasting insulin Wald ratio OR = 1.02, 95% C.I, 0.37-2.78, p = 0.975), high-density lipoprotein (Wald ratio OR = 1.00, 95% C.I., 0.85-1.16; p = 0.849), suggesting that the associations could be fully explained by inflammation. One potential limitation of the study is that the full range of gene products from the genetic variants we used as proxies for the exposures is unknown, and so we are unable to comment on potential biological mechanisms of association other than inflammation, which may also be relevant. Conclusions Our findings support a role for inflammation as a common cause for insulin resistance and schizophrenia, which may at least partly explain why the traits commonly co-occur in clinical practice. Inflammation and immune pathways may represent novel therapeutic targets for the prevention or treatment of schizophrenia and comorbid insulin resistance. Future work is needed to understand how inflammation may contribute to the risk of schizophrenia and insulin resistance., Author(s): Benjamin I. Perry 1,2,*, Stephen Burgess 3, Hannah J. Jones 4,5, Stan Zammit 4,5,6, Rachel Upthegrove 7, Amy M. Mason 8, Felix R. Day 9, Claudia Langenberg 9, Nicholas [...]
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- 2021
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43. Associations of autozygosity with a broad range of human phenotypes
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Clark, David W, Okada, Yukinori, Moore, Kristjan H S, Mason, Dan, Pirastu, Nicola, Gandin, Ilaria, Mattsson, Hannele, Barnes, Catriona L K, Lin, Kuang, Zhao, Jing Hua, Deelen, Patrick, Rohde, Rebecca, Schurmann, Claudia, Guo, Xiuqing, Giulianini, Franco, Zhang, Weihua, Medina-Gomez, Carolina, Karlsson, Robert, Bao, Yanchun, Bartz, Traci M, Baumbach, Clemens, Biino, Ginevra, Bixley, Matthew J, Brumat, Marco, Chai, Jin-Fang, Corre, Tanguy, Cousminer, Diana L, Dekker, Annelot M, Eccles, David A, van Eijk, Kristel R, Fuchsberger, Christian, Gao, He, Germain, Marine, Gordon, Scott D, de Haan, Hugoline G, Harris, Sarah E, Hofer, Edith, Huerta-Chagoya, Alicia, Igartua, Catherine, Jansen, Iris E, Jia, Yucheng, Kacprowski, Tim, Karlsson, Torgny, Kleber, Marcus E, Li, Shengchao Alfred, Li-Gao, Ruifang, Mahajan, Anubha, Matsuda, Koichi, Meidtner, Karina, Meng, Weihua, Montasser, May E, van der Most, Peter J, Munz, Matthias, Nutile, Teresa, Palviainen, Teemu, Prasad, Gauri, Prasad, Rashmi B, Priyanka, Tallapragada Divya Sri, Rizzi, Federica, Salvi, Erika, Sapkota, Bishwa R, Shriner, Daniel, Skotte, Line, Smart, Melissa C, Smith, Albert Vernon, van der Spek, Ashley, Spracklen, Cassandra N, Strawbridge, Rona J, Tajuddin, Salman M, Trompet, Stella, Turman, Constance, Verweij, Niek, Viberti, Clara, Wang, Lihua, Warren, Helen R, Wootton, Robyn E, Yanek, Lisa R, Yao, Jie, Yousri, Noha A, Zhao, Wei, Adeyemo, Adebowale A, Afaq, Saima, Aguilar-Salinas, Carlos Alberto, Akiyama, Masato, Albert, Matthew L, Allison, Matthew A, Alver, Maris, Aung, Tin, Azizi, Fereidoun, Bentley, Amy R, Boeing, Heiner, Boerwinkle, Eric, Borja, Judith B, de Borst, Gert J, Bottinger, Erwin P, Broer, Linda, Campbell, Harry, Chanock, Stephen, Chee, Miao-Li, Chen, Guanjie, Chen, Yii-Der I, Chen, Zhengming, Chiu, Yen-Feng, Cocca, Massimiliano, Collins, Francis S, Concas, Maria Pina, Corley, Janie, Cugliari, Giovanni, van Dam, Rob M, Damulina, Anna, Daneshpour, Maryam S, Day, Felix R, Delgado, Graciela E, Dhana, Klodian, Doney, Alexander S F, Dörr, Marcus, Doumatey, Ayo P, Dzimiri, Nduna, Ebenesersdóttir, S Sunna, Elliott, Joshua, Elliott, Paul, Ewert, Ralf, Felix, Janine F, Fischer, Krista, Freedman, Barry I, Girotto, Giorgia, Goel, Anuj, Gögele, Martin, Goodarzi, Mark O, Graff, Mariaelisa, Granot-Hershkovitz, Einat, Grodstein, Francine, Guarrera, Simonetta, Gudbjartsson, Daniel F, Guity, Kamran, Gunnarsson, Bjarni, Guo, Yu, Hagenaars, Saskia P, Haiman, Christopher A, Halevy, Avner, Harris, Tamara B, Hedayati, Mehdi, van Heel, David A, Hirata, Makoto, Höfer, Imo, Hsiung, Chao Agnes, Huang, Jinyan, Hung, Yi-Jen, Ikram, M Arfan, Jagadeesan, Anuradha, Jousilahti, Pekka, Kamatani, Yoichiro, Kanai, Masahiro, Kerrison, Nicola D, Kessler, Thorsten, Khaw, Kay-Tee, Khor, Chiea Chuen, de Kleijn, Dominique P V, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter, Krämer, Bernhard K, Kutalik, Zoltán, Kuusisto, Johanna, Langenberg, Claudia, Launer, Lenore J, Lawlor, Deborah A, Lee, I-Te, Lee, Wen-Jane, Lerch, Markus M, Li, Liming, Liu, Jianjun, Loh, Marie, London, Stephanie J, Loomis, Stephanie, Lu, Yingchang, Luan, Jian’an, Mägi, Reedik, Manichaikul, Ani W, Manunta, Paolo, Másson, Gísli, Matoba, Nana, Mei, Xue W, Meisinger, Christa, Meitinger, Thomas, Mezzavilla, Massimo, Milani, Lili, Millwood, Iona Y, Momozawa, Yukihide, Moore, Amy, Morange, Pierre-Emmanuel, Moreno-Macías, Hortensia, Mori, Trevor A, Morrison, Alanna C, Muka, Taulant, Murakami, Yoshinori, Murray, Alison D, de Mutsert, Renée, Mychaleckyj, Josyf C, Nalls, Mike A, Nauck, Matthias, Neville, Matt J, Nolte, Ilja M, Ong, Ken K, Orozco, Lorena, Padmanabhan, Sandosh, Pálsson, Gunnar, Pankow, James S, Pattaro, Cristian, Pattie, Alison, Polasek, Ozren, Poulter, Neil, Pramstaller, Peter P, Quintana-Murci, Lluis, Räikkönen, Katri, Ralhan, Sarju, Rao, Dabeeru C, van Rheenen, Wouter, Rich, Stephen S, Ridker, Paul M, Rietveld, Cornelius A, Robino, Antonietta, van Rooij, Frank J A, Ruggiero, Daniela, Saba, Yasaman, Sabanayagam, Charumathi, Sabater-Lleal, Maria, Sala, Cinzia Felicita, Salomaa, Veikko, Sandow, Kevin, Schmidt, Helena, Scott, Laura J, Scott, William R, Sedaghati-Khayat, Bahareh, Sennblad, Bengt, van Setten, Jessica, Sever, Peter J, Sheu, Wayne H-H, Shi, Yuan, Shrestha, Smeeta, Shukla, Sharvari Rahul, Sigurdsson, Jon K, Sikka, Timo Tonis, Singh, Jai Rup, Smith, Blair H, Stančáková, Alena, Stanton, Alice, Starr, John M, Stefansdottir, Lilja, Straker, Leon, Sulem, Patrick, Sveinbjornsson, Gardar, Swertz, Morris A, Taylor, Adele M, Taylor, Kent D, Terzikhan, Natalie, Tham, Yih-Chung, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tillander, Annika, Tracy, Russell P, Tusié-Luna, Teresa, Tzoulaki, Ioanna, Vaccargiu, Simona, Vangipurapu, Jagadish, Veldink, Jan H, Vitart, Veronique, Völker, Uwe, Vuoksimaa, Eero, Wakil, Salma M, Waldenberger, Melanie, Wander, Gurpreet S, Wang, Ya Xing, Wareham, Nicholas J, Wild, Sarah, Yajnik, Chittaranjan S, Yuan, Jian-Min, Zeng, Lingyao, Zhang, Liang, Zhou, Jie, Amin, Najaf, Asselbergs, Folkert W, Bakker, Stephan J L, Becker, Diane M, Lehne, Benjamin, Bennett, David A, van den Berg, Leonard H, Berndt, Sonja I, Bharadwaj, Dwaipayan, Bielak, Lawrence F, Bochud, Murielle, Boehnke, Mike, Bouchard, Claude, Bradfield, Jonathan P, Brody, Jennifer A, Campbell, Archie, Carmi, Shai, Caulfield, Mark J, Cesarini, David, Chambers, John C, Chandak, Giriraj Ratan, Cheng, Ching-Yu, Ciullo, Marina, Cornelis, Marilyn, Cusi, Daniele, Smith, George Davey, Deary, Ian J, Dorajoo, Rajkumar, van Duijn, Cornelia M, Ellinghaus, David, Erdmann, Jeanette, Eriksson, Johan G, Evangelou, Evangelos, Evans, Michele K, Faul, Jessica D, Feenstra, Bjarke, Feitosa, Mary, Foisy, Sylvain, Franke, Andre, Friedlander, Yechiel, Gasparini, Paolo, Gieger, Christian, Gonzalez, Clicerio, Goyette, Philippe, Grant, Struan F A, Griffiths, Lyn R, Groop, Leif, Gudnason, Vilmundur, Gyllensten, Ulf, Hakonarson, Hakon, Hamsten, Anders, van der Harst, Pim, Heng, Chew-Kiat, Hicks, Andrew A, Hochner, Hagit, Huikuri, Heikki, Hunt, Steven C, Jaddoe, Vincent W V, De Jager, Philip L, Johannesson, Magnus, Johansson, Åsa, Jonas, Jost B, Jukema, J Wouter, Junttila, Juhani, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kumari, Meena, Laakso, Markku, van der Laan, Sander W, Lahti, Jari, Laudes, Matthias, Lea, Rodney A, Lieb, Wolfgang, Lumley, Thomas, Martin, Nicholas G, März, Winfried, Matullo, Giuseppe, McCarthy, Mark I, Medland, Sarah E, Merriman, Tony R, Metspalu, Andres, Meyer, Brian F, Mohlke, Karen L, Montgomery, Grant W, Mook-Kanamori, Dennis, Munroe, Patricia B, North, Kari E, Nyholt, Dale R, O’connell, Jeffery R, Ober, Carole, Oldehinkel, Albertine J, Palmas, Walter, Palmer, Colin, Pasterkamp, Gerard G, Patin, Etienne, Pennell, Craig E, Perusse, Louis, Peyser, Patricia A, Pirastu, Mario, Polderman, Tinca J. C., Porteous, David J, Posthuma, Danielle, Psaty, Bruce M, Rioux, John D, Rivadeneira, Fernando, Rotimi, Charles, Rotter, Jerome I, Rudan, Igor, Den Ruijter, Hester M, Sanghera, Dharambir K, Sattar, Naveed, Schmidt, Reinhold, Schulze, Matthias B, Schunkert, Heribert, Scott, Robert A, Shuldiner, Alan R, Sim, Xueling, Small, Neil, Smith, Jennifer A, Sotoodehnia, Nona, Tai, E-Shyong, Teumer, Alexander, Timpson, Nicholas J, Toniolo, Daniela, Tregouet, David-Alexandre, Tuomi, Tiinamaija, Vollenweider, Peter, Wang, Carol A, Weir, David R, Whitfield, John B, Wijmenga, Cisca, Wong, Tien-Yin, Wright, John, Yang, Jingyun, Yu, Lei, Zemel, Babette S, Zonderman, Alan B, Perola, Markus, Magnusson, Patrik K. E., Uitterlinden, André G, Kooner, Jaspal S, Chasman, Daniel I, Loos, Ruth J. F., Franceschini, Nora, Franke, Lude, Haley, Chris S, Hayward, Caroline, Walters, Robin G, Perry, John R. B., Esko, Tōnu, Helgason, Agnar, Stefansson, Kari, Joshi, Peter K, Kubo, Michiaki, and Wilson, James F
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- 2019
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44. Assessing the causal association of glycine with risk of cardio-metabolic diseases
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Wittemans, Laura B. L., Lotta, Luca A., Oliver-Williams, Clare, Stewart, Isobel D., Surendran, Praveen, Karthikeyan, Savita, Day, Felix R., Koulman, Albert, Imamura, Fumiaki, Zeng, Lingyao, Erdmann, Jeanette, Schunkert, Heribert, Khaw, Kay-Tee, Griffin, Julian L., Forouhi, Nita G., Scott, Robert A., Wood, Angela M., Burgess, Stephen, Howson, Joanna M. M., Danesh, John, Wareham, Nicholas J., Butterworth, Adam S., and Langenberg, Claudia
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- 2019
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45. Season of birth is associated with birth weight, pubertal timing, adult body size and educational attainment: a UK Biobank study
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Day, Felix R., Forouhi, Nita G., Ong, Ken K., and Perry, John R.B.
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- 2015
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46. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis
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Zheng, Ju-Sheng, Luan, Jian'an, Sofianopoulou, Eleni, Sharp, Stephen J., Day, Felix R., Imamura, Fumiaki, Gundersen, Thomas E., Lotta, Luca A., Sluijs, Ivonne, Stewart, Isobel D., Shah, Rupal L., van der Schouw, Yvonne T., Wheeler, Eleanor, Ardanaz, Eva, Boeing, Heiner, Dorronsoro, Miren, Dahm, Christina C., Dimou, Niki, El-Fatouhi, Douae, Franks, Paul W., Fagherazzi, Guy, Grioni, Sara, Huerta, José María, Heath, Alicia K., Hansen, Louise, Jenab, Mazda, Jakszyn, Paula, Kaaks, Rudolf, Kühn, Tilman, Khaw, Kay-Tee, Laouali, Nasser, Masala, Giovanna, Nilsson, Peter M., Overvad, Kim, Olsen, Anja, Panico, Salvatore, Quirós, J. Ramón, Rolandsson, Olov, Rodríguez-Barranco, Miguel, Sacerdote, Carlotta, Spijkerman, Annemieke M. W., Tong, Tammy Y. N., Tumino, Rosario, Tsilidis, Konstantinos K., Danesh, John, Riboli, Elio, Butterworth, Adam S., Langenberg, Claudia, Forouhi, Nita G., and Wareham, Nicholas J.
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Vitamin D deficiency -- Complications and side effects -- Physiological aspects -- Genetic aspects ,Type 2 diabetes -- Risk factors -- Development and progression -- Genetic aspects ,Biological sciences - Abstract
Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D.sub.3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D.sub.3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D.sub.3 (N = 40,562), and C3-epi-25(OH)D.sub.3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D.sub.3 and 3 loci associated with C3-epi-25(OH)D.sub.3 . Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D.sub.3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D.sub.3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D.sub.3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D.sub.3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D., Author(s): Ju-Sheng Zheng 1,2,*, Jian'an Luan 1, Eleni Sofianopoulou 3,4, Stephen J. Sharp 1, Felix R. Day 1, Fumiaki Imamura 1, Thomas E. Gundersen 5, Luca A. Lotta 1, Ivonne [...]
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- 2020
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47. IDENTIFICATION OF NOVEL PCOS-RISK ALLELES BY LARGE-SCALE GENOME WIDE META-ANALYSIS PROVIDES NEW INSIGHTS INTO BIOLOGICAL MECHANISMS AND CLINICAL HEALTH OUTCOMES
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Moolhuijsen, Loes, primary, Day, Felix R., additional, Karaderi, Tugce, additional, Mullin, Benjamin H., additional, Zhu, Jia, additional, Gualdo, Natàlia Pujol, additional, Actkins, Ky'Era V., additional, Welt, Corrine K., additional, Louwers, Yvonne, additional, Visser, Jenny A., additional, and Laven, Joop, additional
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- 2022
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48. Detection and characterization of male sex chromosome abnormalities in the UK Biobank study
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Zhao, Yajie, primary, Gardner, Eugene J., additional, Tuke, Marcus A., additional, Zhang, Huairen, additional, Pietzner, Maik, additional, Koprulu, Mine, additional, Jia, Raina Y., additional, Ruth, Katherine S., additional, Wood, Andrew R., additional, Beaumont, Robin N., additional, Tyrrell, Jessica, additional, Jones, Samuel E., additional, Lango Allen, Hana, additional, Day, Felix R., additional, Langenberg, Claudia, additional, Frayling, Timothy M., additional, Weedon, Michael N., additional, Perry, John R.B., additional, Ong, Ken K., additional, and Murray, Anna, additional
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- 2022
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49. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
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Mills, Melinda C, Tropf, Felix C, Brazel, David M, van Zuydam, Natalie, Vaez, Ahmad, eQTLGen Consortium, BIOS Consortium, Human Reproductive Behaviour Consortium, Pers, Tune H, Snieder, Harold, Perry, John RB, Ong, Ken K, den Hoed, Marcel, Barban, Nicola, Day, Felix R, Mills, Melinda C [0000-0003-1704-0001], Tropf, Felix C [0000-0003-2445-515X], Brazel, David M [0000-0001-5361-2498], Vaez, Ahmad [0000-0001-9048-3795], Pers, Tune H [0000-0003-0207-4831], Snieder, Harold [0000-0003-1949-2298], Perry, John RB [0000-0001-6483-3771], Ong, Ken K [0000-0003-4689-7530], den Hoed, Marcel [0000-0001-8081-428X], Barban, Nicola [0000-0002-4362-4652], Day, Felix R [0000-0003-3789-7651], and Apollo - University of Cambridge Repository
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Male ,Adolescent ,Reproduction ,Age Factors ,Coitus ,Parturition ,Humans ,Female ,Polymorphism, Single Nucleotide ,Genetic Association Studies - Abstract
Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5-6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4-14%] for women born in 1940 to 22% [CI = 19-25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.
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- 2021
50. Genetic risk score for adult body mass index associations with childhood and adolescent weight gain in an African population
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Munthali, Richard J., Sahibdeen, Venesa, Kagura, Juliana, Hendry, Liesl M., Norris, Shane A., Ong, Ken K., Day, Felix R., and Lombard, Zané
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- 2018
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