Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

Autor: Reppe, Sjur, Wang, Yunpeng, Thompson, Wesley K., McEvoy, Linda K., Schork, Andrew J., Zuber, Verena, LeBlanc, Marissa, Bettella, Francesco, Mills, Ian G., Desikan, Rahul S., Djurovic, Srdjan, Gautvik, Kaare M., Dale, Anders M., Andreassen, Ole A., Estrada, Karol, Styrkarsdottir, Unnur, Evangelou, Evangelos, Hsu, Yi Hsiang, Duncan, Emma L., Ntzani, Evangelia E., Oei, Ling, Albagha, Omar M.E., Amin, Najaf, Kemp, John P., Koller, Daniel L., Li, Guo, Liu, Ching Ti, Minster, Ryan L., Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su Mei, Yerges-Armstrong, Laura M., Zheng, Hou Feng, Alonso, Nerea, Eriksson, Joel, Kammerer, Candace M., Kaptoge, Stephen K., Leo, Paul J., Thorleifsson, Gudmar, Wilson, Scott G., Wilson, James F., Aalto, Ville, Alen, Markku, Aragaki, Aaron K., Aspelund, Thor, Center, Jacqueline R., Dailiana, Zoe, Duggan, David J., Garcia, Melissa, Garcia-Giralt, Natàlia, Giroux, Sylvie, Hallmans, Göran, Hocking, Lynne J., Husted, Lise Bjerre, Jameson, Karen A., Khusainova, Rita, Kim, Ghi Su, Kooperberg, Charles, Koromila, Theodora, Kruk, Marcin, Laaksonen, Marika, Lacroix, Andrea Z., Lee, Seung Hun, Leung, Ping C., Lewis, Joshua R., Masi, Laura, Mencej-Bedrac, Simona, Nguyen, Tuan V., Nogues, Xavier, Patel, Millan S., Prezelj, Janez, Rose, Lynda M., Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V., Svensson, Olle, Trompet, Stella, Trummer, Olivia, Van Schoor, Natasja M., Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M., Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung Min, Kollia, Panagoula, Langdahl, Bente Lomholt, Leslie, William D., Lips, Paul, Ljunggren, Östen, Lorenc, Roman S., Marc, Janja, Mellström, Dan, Obermayer-Pietsch, Barbara, Olmos, José M., Pettersson-Kymmer, Ulrika, Reid, David M., Riancho, José A., Ridker, Paul M., Rousseau, François, Slagboom, P. Eline, Tang, Nelson L.S., Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, María T., Aulchenko, Yurii S., Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gómez, Carolina, Palsson, Stefan Th, Rotter, Jerome I., Sigurdsson, Gunnar, Van Meurs, Joyce B.J., Verlaan, Dominique, Williams, Frances M.K., Wood, Andrew R., Zhou, Yanhua, Pastinen, Tomi, Raychaudhuri, Soumya, Cauley, Jane A., Chasman, Daniel I., Clark, Graeme R., Cummings, Steven R., Danoy, Patrick, Dennison, Elaine M., Eastell, Richard, Eisman, John A., Gudnason, Vilmundur, Hofman, Albert, Jackson, Rebecca D., Jones, Graeme, Jukema, J. Wouter, Khaw, Kay Tee, Lehtimäki, Terho, Liu, Yongmei, Lorentzon, Mattias, McCloskey, Eugene, Mitchell, Braxton D., Nandakumar, Kannabiran, Nicholson, Geoffrey C., Oostra, Ben A., Peacock, Munro, Pols, Huibert A.P., Prince, Richard L., Raitakari, Olli, Reid, Ian R., Robbins, John, Sambrook, Philip N., Sham, Pak Chung, Shuldiner, Alan R., Tylavsky, Frances A., Van Duijn, Cornelia M., Wareham, Nick J., Cupples, L. Adrienne, Econs, Michael J., Evans, David M., Harris, Tamara B., Kung, Annie Wai Chee, Psaty, Bruce M., Reeve, Jonathan, Spector, Timothy D., Streeten, Elizabeth A., Zillikens, M. Carola, Thorsteinsdottir, Unnur, Ohlsson, Claes, Karasik, David, Richards, J. Brent, Brown, Matthew A., Stefansson, Kari, Uitterlinden, André G., Ralston, Stuart H., Ioannidis, John P.A., Kiel, Douglas P., Rivadeneira, Fernando
Přispěvatelé: Epidemiology and Data Science, EMGO - Musculoskeletal health, Internal medicine
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: PLoS ONE, 10(12):e0144531. Public Library of Science
Reppe, S, Wang, Y, Thompson, W K, McEvoy, L K, Schork, A J, Zuber, V, LeBlanc, M, Bettella, F, Mills, I G, Desikan, R S, Djurovic, S, Gautvik, K M, Dale, A M, Andreassen, O A, Estrada, K, Styrkarsdottir, U, Evangelou, E, Hsu, Y H, Duncan, E L, Ntzani, E E, Oei, L, Albagha, O M E, Amin, N, Kemp, J P, Koller, D L, Li, G, Liu, C T, Minster, R L, Moayyeri, A, Vandenput, L, Willner, D, Xiao, S M, Yerges-Armstrong, L M, Zheng, H F, Alonso, N, Eriksson, J, Kammerer, C M, Kaptoge, S K, Leo, P J, Thorleifsson, G, Wilson, S G, Wilson, J F, Aalto, V, Alen, M, Aragaki, A K, Aspelund, T, Center, J R, Dailiana, Z, Duggan, D J, Garcia, M, Garcia-Giralt, N, Giroux, S, Hallmans, G, Hocking, L J, Husted, L B, Jameson, K A, Khusainova, R, Kim, G S, Kooperberg, C, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, A Z, Lee, S H, Leung, P C, Lewis, J R, Masi, L, Mencej-Bedrac, S, Nguyen, T V, Nogues, X, Patel, M S, Prezelj, J, Rose, L M, Scollen, S, Siggeirsdottir, K, Smith, A V, Svensson, O, Trompet, S, Trummer, O, Van Schoor, N M, Woo, J, Zhu, K, Balcells, S, Brandi, M L, Buckley, B M, Cheng, S, Christiansen, C, Cooper, C, Dedoussis, G, Ford, I, Frost, M, Goltzman, D, González-Macías, J, Kähönen, M, Karlsson, M, Khusnutdinova, E, Koh, J M, Kollia, P, Langdahl, B L, Leslie, W D, Lips, P, Ljunggren, Ö, Lorenc, R S, Marc, J, Mellström, D, Obermayer-Pietsch, B, Olmos, J M, Pettersson-Kymmer, U, Reid, D M, Riancho, J A, Ridker, P M, Rousseau, F, Slagboom, P E, Tang, N L S, Urreizti, R, Van Hul, W, Viikari, J, Zarrabeitia, M T, Aulchenko, Y S, Castano-Betancourt, M, Grundberg, E, Herrera, L, Ingvarsson, T, Johannsdottir, H, Kwan, T, Li, R, Luben, R, Medina-Gómez, C, Palsson, S T, Rotter, J I, Sigurdsson, G, Van Meurs, J B J, Verlaan, D, Williams, F M K, Wood, A R, Zhou, Y, Pastinen, T, Raychaudhuri, S, Cauley, J A, Chasman, D I, Clark, G R, Cummings, S R, Danoy, P, Dennison, E M, Eastell, R, Eisman, J A, Gudnason, V, Hofman, A, Jackson, R D, Jones, G, Jukema, J W, Khaw, K T, Lehtimäki, T, Liu, Y, Lorentzon, M, McCloskey, E, Mitchell, B D, Nandakumar, K, Nicholson, G C, Oostra, B A, Peacock, M, Pols, H A P, Prince, R L, Raitakari, O, Reid, I R, Robbins, J, Sambrook, P N, Sham, P C, Shuldiner, A R, Tylavsky, F A, Van Duijn, C M, Wareham, N J, Cupples, L A, Econs, M J, Evans, D M, Harris, T B, Kung, A W C, Psaty, B M, Reeve, J, Spector, T D, Streeten, E A, Zillikens, M C, Thorsteinsdottir, U, Ohlsson, C, Karasik, D, Richards, J B, Brown, M A, Stefansson, K, Uitterlinden, A G, Ralston, S H, Ioannidis, J P A, Kiel, D P, Rivadeneira, F & GEFOS Consortium 2015, ' Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci ', PLoS ONE, vol. 10, no. 12, e0144531 . https://doi.org/10.1371/journal.pone.0144531
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0144531
Popis: Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.
Databáze: OpenAIRE
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