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

Author

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
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2. Publisher Correction: Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author

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

Author

Kilpelainen, Tuomas O., Martin-Carli, Jayne Frances, Skowronski, Alicja Anna, Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F., Hedman, Asa K., Drong, Alexander W., Hayes, James E., Zhao, Jinghua, Pers, Tune H., Schick, Ursula, Grarup, Niels, Kutalik, Zolt��n, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytik��inen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian���an, Del Greco M, Fabiola, Pasko, Dorota, Renstr��m, Frida, Willems, Sara M., Mahajan, Anubha, Rose, Lynda M., Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E., P��russe, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S., Sung, Yun Ju, Ramos, Yolande F., Amin, Najaf, Amuzu, Antoinette, Barroso, In��s, Bellis, Claire, Blangero, John, Buckley, Brendan M., B��hringer, Stefan, Chen, Yii-Der I., de Craen, Anton J. N., 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, G��ran, 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., J��rgensen, Marit E., J��rgensen, 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., M��nnist��, Satu, Nalls, Mike A., Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rathmann, Wolfgang, Rice, Treva K., Richards, J. Brent, Ridker, Paul M., Sattar, Naveed, Savage, David B., S��derberg, Stefan, Timpson, Nicholas J., Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Wid��n, Elisabeth, Wood, Andrew R., Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, S��rensen, Thorkild I. A., Sarzynski, Mark A., Rao, D. C., Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andr�� G., Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G., Heli��vaara, Markku, Knekt, Paul B., Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K., Viikari, Jorma S., K��h��nen, Mika, Lehtim��ki, Terho, Raitakari, Olli T., Mellstr��m, Dan, Lorentzon, Mattias, Casas, Juan P., Bandinelli, Stefanie, M��rz, Winfried, Isaacs, Aaron, van Dijk, Ko W., van Duijn, Cornelia M., Harris, Tamara B., Bouchard, Claude, Allison, Matthew A., Chasman, Daniel I., Ohlsson, Claes, Lind, Lars, Scott, Robert A., Langenberg, Claudia, Wareham, Nicholas J., Ferrucci, Luigi, Frayling, Timothy M., Pramstaller, Peter P., Borecki, Ingrid B., Waterworth, Dawn M., Bergmann, Sven, Waeber, G��rard, and Vollenweider, Peter

Subjects
Leptin, Meta-analysis, Molecular biology, FOS: Biological sciences, digestive, oral, and skin physiology, Genetics, hormones, hormone substitutes, and hormone antagonists
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

Published
2016
Full Text
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4. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author

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, Greco M, Fabiola Del, 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 J N, 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, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, Loos, Ruth J F, 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, Greco M, Fabiola Del, 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 J N, 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, Savage, David B, Söderberg, Stefan, Timpson, Nicholas J, Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widén, Elisabeth, Wood, Andrew R, Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sørensen, Thorkild I A, Sarzynski, Mark A, Rao, D C, Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G, Heliövaara, Markku, Knekt, Paul B, Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K, Viikari, Jorma S, Kähönen, Mika, Lehtimäki, Terho, Raitakari, Olli T, Mellström, Dan, Lorentzon, Mattias, Casas, Juan P, Bandinelli, Stefanie, März, Winfried, Isaacs, Aaron, van Dijk, Ko W, van Duijn, Cornelia M, Harris, Tamara B, Bouchard, Claude, Allison, Matthew A, Chasman, Daniel I, Ohlsson, Claes, Lind, Lars, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, Ferrucci, Luigi, Frayling, Timothy M, Pramstaller, Peter P, Borecki, Ingrid B, Waterworth, Dawn M, Bergmann, Sven, Waeber, Gérard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B, Eline Slagboom, P, Grallert, Harald, Spector, Tim D, Jukema, J W, Klein, Robert J, Schadt, Erik E, Franks, Paul W, Lindgren, Cecilia M, Leibel, Rudolph L, and Loos, Ruth J F

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<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

Published
2016
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5. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author

University of Helsinki, Helsinki Collegium for Advanced Studies, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Hospital for Children and Adolescents, University of Helsinki, Clinicum, Kilpelainen, Tuomas O., Carli, Jayne F. Martin, Skowronski, Alicja A., Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F., Hedman, Asa K., Drong, Alexander W., Hayes, James E., Zhao, Jinghua, Pers, Tune H., Schick, Ursula, Grarup, Niels, Kutalik, Zoltan, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikainen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Del Greco M, Fabiola, Pasko, Dorota, Renstrom, Frida, Willems, Sara M., Mahajan, Anubha, Rose, Lynda M., Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E., Perusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S., Sung, Yun Ju, Ramos, Yolande F., Amin, Najaf, Amuzu, Antoinette, Barroso, Ines, Bellis, Claire, Blangero, John, Buckley, Brendan M., Boehringer, Stefan, Chen, Yii-Der I., de Craen, Anton J. N., 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, Goran, 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., Jorgensen, Marit E., Jorgensen, 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., Mannisto, Satu, Nalls, Mike A., Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rathmann, Wolfgang, Rice, Treva K., Richards, J. Brent, Ridker, Paul M., Sattar, Naveed, Savage, David B., Soderberg, Stefan, Timpson, Nicholas J., Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widen, Elisabeth, Wood, Andrew R., Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sorensen, Thorkild I. A., Sarzynski, Mark A., Rao, D. C., Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G., Heliovaara, Markku, Knekt, Paul B., Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K., Viikari, Jorma S., Kahonen, Mika, Lehtimaki, Terho, Raitakari, Olli T., Mellstrom, Dan, Lorentzon, Mattias, Casas, Juan P., Bandinelli, Stefanie, Maerz, Winfried, Isaacs, Aaron, van Dijk, Ko W., van Duijn, Cornelia M., Harris, Tamara B., Bouchard, Claude, Allison, Matthew A., Chasman, Daniel I., Ohlsson, Claes, Lind, Lars, Scott, Robert A., Langenberg, Claudia, Wareham, Nicholas J., Ferrucci, Luigi, Frayling, Timothy M., Pramstaller, Peter P., Borecki, Ingrid B., Waterworth, Dawn M., Bergmann, Sven, Waeber, Gerard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B., Slagboom, P. Eline, Grallert, Harald, Spector, Tim D., Jukema, J. W., Klein, Robert J., Schadt, Erik E., Franks, Paul W., Lindgren, Cecilia M., Leibel, Rudolph L., Loos, Ruth J. F., University of Helsinki, Helsinki Collegium for Advanced Studies, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Hospital for Children and Adolescents, University of Helsinki, Clinicum, Kilpelainen, Tuomas O., Carli, Jayne F. Martin, Skowronski, Alicja A., Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F., Hedman, Asa K., Drong, Alexander W., Hayes, James E., Zhao, Jinghua, Pers, Tune H., Schick, Ursula, Grarup, Niels, Kutalik, Zoltan, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikainen, Leo-Pekka, Eriksson, Joel, Henneman, Peter, Lahti, Jari, Tanaka, Toshiko, Luan, Jian'an, Del Greco M, Fabiola, Pasko, Dorota, Renstrom, Frida, Willems, Sara M., Mahajan, Anubha, Rose, Lynda M., Guo, Xiuqing, Liu, Yongmei, Kleber, Marcus E., Perusse, Louis, Gaunt, Tom, Ahluwalia, Tarunveer S., Sung, Yun Ju, Ramos, Yolande F., Amin, Najaf, Amuzu, Antoinette, Barroso, Ines, Bellis, Claire, Blangero, John, Buckley, Brendan M., Boehringer, Stefan, Chen, Yii-Der I., de Craen, Anton J. N., 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, Goran, 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., Jorgensen, Marit E., Jorgensen, 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., Mannisto, Satu, Nalls, Mike A., Paternoster, Lavinia, Peters, Annette, Pradhan, Aruna D., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rathmann, Wolfgang, Rice, Treva K., Richards, J. Brent, Ridker, Paul M., Sattar, Naveed, Savage, David B., Soderberg, Stefan, Timpson, Nicholas J., Vandenput, Liesbeth, van Heemst, Diana, Uh, Hae-Won, Vohl, Marie-Claude, Walker, Mark, Wichmann, Heinz-Erich, Widen, Elisabeth, Wood, Andrew R., Yao, Jie, Zeller, Tanja, Zhang, Yiying, Meulenbelt, Ingrid, Kloppenburg, Margreet, Astrup, Arne, Sorensen, Thorkild I. A., Sarzynski, Mark A., Rao, D. C., Jousilahti, Pekka, Vartiainen, Erkki, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Kajantie, Eero, Osmond, Clive, Palotie, Aarno, Eriksson, Johan G., Heliovaara, Markku, Knekt, Paul B., Koskinen, Seppo, Jula, Antti, Perola, Markus, Huupponen, Risto K., Viikari, Jorma S., Kahonen, Mika, Lehtimaki, Terho, Raitakari, Olli T., Mellstrom, Dan, Lorentzon, Mattias, Casas, Juan P., Bandinelli, Stefanie, Maerz, Winfried, Isaacs, Aaron, van Dijk, Ko W., van Duijn, Cornelia M., Harris, Tamara B., Bouchard, Claude, Allison, Matthew A., Chasman, Daniel I., Ohlsson, Claes, Lind, Lars, Scott, Robert A., Langenberg, Claudia, Wareham, Nicholas J., Ferrucci, Luigi, Frayling, Timothy M., Pramstaller, Peter P., Borecki, Ingrid B., Waterworth, Dawn M., Bergmann, Sven, Waeber, Gerard, Vollenweider, Peter, Vestergaard, Henrik, Hansen, Torben, Pedersen, Oluf, Hu, Frank B., Slagboom, P. Eline, Grallert, Harald, Spector, Tim D., Jukema, J. W., Klein, Robert J., Schadt, Erik E., Franks, Paul W., Lindgren, Cecilia M., Leibel, Rudolph L., and Loos, Ruth J. F.

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 <10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P <5 x 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

Published
2016

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

Author

Kilpeläinen, Tuomas O., primary, Carli, Jayne F. Martin, additional, Skowronski, Alicja A., additional, Sun, Qi, additional, Kriebel, Jennifer, additional, Feitosa, Mary F, additional, Hedman, Åsa K., additional, Drong, Alexander W., additional, Hayes, James E., additional, Zhao, Jinghua, additional, Pers, Tune H., additional, Schick, Ursula, additional, Grarup, Niels, additional, Kutalik, Zoltán, additional, Trompet, Stella, additional, Mangino, Massimo, additional, Kristiansson, Kati, additional, Beekman, Marian, additional, Lyytikäinen, Leo-Pekka, additional, Eriksson, Joel, additional, Henneman, Peter, additional, Lahti, Jari, additional, Tanaka, Toshiko, additional, Luan, Jian’an, additional, Greco M, Fabiola Del, additional, Pasko, Dorota, additional, Renström, Frida, additional, Willems, Sara M., additional, Mahajan, Anubha, additional, Rose, Lynda M., additional, Guo, Xiuqing, additional, Liu, Yongmei, additional, Kleber, Marcus E., additional, Pérusse, Louis, additional, Gaunt, Tom, additional, Ahluwalia, Tarunveer S., additional, Ju Sung, Yun, additional, Ramos, Yolande F., additional, Amin, Najaf, additional, Amuzu, Antoinette, additional, Barroso, Inês, additional, Bellis, Claire, additional, Blangero, John, additional, Buckley, Brendan M., additional, Böhringer, Stefan, additional, I Chen, Yii-Der, additional, de Craen, Anton J. N., additional, Crosslin, David R., additional, Dale, Caroline E., additional, Dastani, Zari, additional, Day, Felix R., additional, Deelen, Joris, additional, Delgado, Graciela E., additional, Demirkan, Ayse, additional, Finucane, Francis M., additional, Ford, Ian, additional, Garcia, Melissa E., additional, Gieger, Christian, additional, Gustafsson, Stefan, additional, Hallmans, Göran, additional, Hankinson, Susan E., additional, Havulinna, Aki S, additional, Herder, Christian, additional, Hernandez, Dena, additional, Hicks, Andrew A., additional, Hunter, David J., additional, Illig, Thomas, additional, Ingelsson, Erik, additional, Ioan-Facsinay, Andreea, additional, Jansson, John-Olov, additional, Jenny, Nancy S., additional, Jørgensen, Marit E., additional, Jørgensen, Torben, additional, Karlsson, Magnus, additional, Koenig, Wolfgang, additional, Kraft, Peter, additional, Kwekkeboom, Joanneke, additional, Laatikainen, Tiina, additional, Ladwig, Karl-Heinz, additional, LeDuc, Charles A., additional, Lowe, Gordon, additional, Lu, Yingchang, additional, Marques-Vidal, Pedro, additional, Meisinger, Christa, additional, Menni, Cristina, additional, Morris, Andrew P., additional, Myers, Richard H., additional, Männistö, Satu, additional, Nalls, Mike A., additional, Paternoster, Lavinia, additional, Peters, Annette, additional, Pradhan, Aruna D., additional, Rankinen, Tuomo, additional, Rasmussen-Torvik, Laura J., additional, Rathmann, Wolfgang, additional, Rice, Treva K., additional, Brent Richards, J, additional, Ridker, Paul M., additional, Sattar, Naveed, additional, Savage, David B., additional, Söderberg, Stefan, additional, Timpson, Nicholas J., additional, Vandenput, Liesbeth, additional, van Heemst, Diana, additional, Uh, Hae-Won, additional, Vohl, Marie-Claude, additional, Walker, Mark, additional, Wichmann, Heinz-Erich, additional, Widén, Elisabeth, additional, Wood, Andrew R., additional, Yao, Jie, additional, Zeller, Tanja, additional, Zhang, Yiying, additional, Meulenbelt, Ingrid, additional, Kloppenburg, Margreet, additional, Astrup, Arne, additional, Sørensen, Thorkild I. A., additional, Sarzynski, Mark A., additional, Rao, D. C., additional, Jousilahti, Pekka, additional, Vartiainen, Erkki, additional, Hofman, Albert, additional, Rivadeneira, Fernando, additional, Uitterlinden, André G., additional, Kajantie, Eero, additional, Osmond, Clive, additional, Palotie, Aarno, additional, Eriksson, Johan G., additional, Heliövaara, Markku, additional, Knekt, Paul B., additional, Koskinen, Seppo, additional, Jula, Antti, additional, Perola, Markus, additional, Huupponen, Risto K., additional, Viikari, Jorma S., additional, Kähönen, Mika, additional, Lehtimäki, Terho, additional, Raitakari, Olli T., additional, Mellström, Dan, additional, Lorentzon, Mattias, additional, Casas, Juan P., additional, Bandinelli, Stefanie, additional, März, Winfried, additional, Isaacs, Aaron, additional, van Dijk, Ko W., additional, van Duijn, Cornelia M., additional, Harris, Tamara B., additional, Bouchard, Claude, additional, Allison, Matthew A., additional, Chasman, Daniel I., additional, Ohlsson, Claes, additional, Lind, Lars, additional, Scott, Robert A., additional, Langenberg, Claudia, additional, Wareham, Nicholas J., additional, Ferrucci, Luigi, additional, Frayling, Timothy M., additional, Pramstaller, Peter P., additional, Borecki, Ingrid B., additional, Waterworth, Dawn M., additional, Bergmann, Sven, additional, Waeber, Gérard, additional, Vollenweider, Peter, additional, Vestergaard, Henrik, additional, Hansen, Torben, additional, Pedersen, Oluf, additional, Hu, Frank B., additional, Eline Slagboom, P, additional, Grallert, Harald, additional, Spector, Tim D., additional, Jukema, J.W., additional, Klein, Robert J., additional, Schadt, Erik E, additional, Franks, Paul W., additional, Lindgren, Cecilia M., additional, Leibel, Rudolph L., additional, and Loos, Ruth J. F., additional

Published
2016
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8. Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Author

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

Abstract

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively. These common variant analyses were supported by exome sequence analysis of ~220,000 women, identifying several genes, including rare loss of function variants in ZNF483 which abolished the impact of polygenic risk. Next, we implicated 660 genes in pubertal development using a combination of in silico variant-to-gene mapping approaches and integration with dynamic gene expression data from mouse embryonic GnRH neurons. This included an uncharacterized G-protein coupled receptor GPR83 , which we demonstrate amplifies signaling of MC3R , a key sensor of nutritional status. Finally, we identified several genes, including ovary-expressed genes involved in DNA damage response that co-localize with signals associated with menopause timing, leading us to hypothesize that the ovarian reserve might signal centrally to trigger puberty. Collectively these findings extend our understanding of the biological complexity of puberty timing and highlight body size dependent and independent mechanisms that potentially link reproductive timing to later life disease., Competing Interests: Competing interests J.R.B.P. and E.J.G. are employed by Adrestia Therapeutics. D.J.T. is employed by Genomics PLC. D.L.C. and J.P.B. are employed by GSK. E.T. is employed by Pfizer. D.A.L. has received support from Roche Disgnostics and Medtroic Ltd for work unrelated to the research in this paper. T.D.S. is co-founder and stakeholder of Zoe Global Ltd. P.A.F. conducts research funded by Amgen, Novartis and Pfizer, he received Honoraria from Roche, Novartis and Pfizer. M.W.B. conducts research funded by Amgen, Novartis and Pfizer.

Published
2023
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