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2. A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy

Author

Mingardo, Enrico, Beaman, Glenda, Grote, Philip, Nordenskjöld, Agneta, Newman, William, Woolf, Adrian S., Eckstein, Markus, Hilger, Alina C., Dworschak, Gabriel C., Rösch, Wolfgang, Ebert, Anne-Karolin, Stein, Raimund, Brusco, Alfredo, Di Grazia, Massimo, Tamer, Ali, Torres, Federico M., Hernandez, Jose L., Erben, Philipp, Maj, Carlo, Olmos, Jose M., Riancho, Jose A., Valero, Carmen, Hostettler, Isabel C., Houlden, Henry, Werring, David J., Schumacher, Johannes, Gehlen, Jan, Giel, Ann-Sophie, Buerfent, Benedikt C., Arkani, Samara, Åkesson, Elisabeth, Rotstein, Emilia, Ludwig, Michael, Holmdahl, Gundela, Giorgio, Elisa, Berettini, Alfredo, Keene, David, Cervellione, Raimondo M., Younsi, Nina, Ortlieb, Melissa, Oswald, Josef, Haid, Bernhard, Promm, Martin, Neissner, Claudia, Hirsch, Karin, Stehr, Maximilian, Schäfer, Frank-Mattias, Schmiedeke, Eberhard, Boemers, Thomas M., van Rooij, Iris A. L. M., Feitz, Wouter F. J., Marcelis, Carlo L. M., Lacher, Martin, Nelson, Jana, Ure, Benno, Fortmann, Caroline, Gale, Daniel P., Chan, Melanie M. Y., Ludwig, Kerstin U., Nöthen, Markus M., Heilmann, Stefanie, Zwink, Nadine, Jenetzky, Ekkehart, Odermatt, Benjamin, Knapp, Michael, and Reutter, Heiko

Published
2022
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6. Blood group O and post-COVID-19 syndrome

Author

Diaz-Salazar, Sara, primary, Navas, Raquel, additional, Sainz-Maza, Laura, additional, Fierro, Patricia, additional, Maamar, Meryam, additional, Artime, Arancha, additional, Basterrechea, Hector, additional, Petitta, Benedetta, additional, Lamadrid, Carlota, additional, Pedraja, Lucia, additional, Gandara-Samperio, Claudia, additional, Pini, Stefanie, additional, Olmos, Jose M., additional, Ramos-Barron, Carmen, additional, Pariente, Emilio, additional, and Hernandez, Jose L, additional

Published
2022
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10. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

Author

Zheng, Hou-Feng, Forgetta, Vincenzo, Hsu, Yi-Hsiang, Estrada, Karol, Rosello-Diez, Alberto, Leo, Paul J., Dahia, Chitra L., Park-Min, Kyung Hyun, Tobias, Jonathan H., Kooperberg, Charles, Kleinman, Aaron, Styrkarsdottir, Unnur, Liu, Ching-Ti, Uggla, Charlotta, Evans, Daniel S., Nielson, Carrie M., Walter, Klaudia, Pettersson-Kymmer, Ulrika, McCarthy, Shane, Eriksson, Joel, Kwan, Tony, Jhamai, Mila, Trajanoska, Katerina, Memari, Yasin, Min, Josine, Huang, Jie, Danecek, Petr, Wilmot, Beth, Li, Rui, Chou, Wen-Chi, Mokry, Lauren E., Moayyeri, Alireza, Claussnitzer, Melina, Cheng, Chia-Ho, Cheung, Warren, Medina-Gómez, Carolina, Ge, Bing, Chen, Shu-Huang, Choi, Kwangbom, Oei, Ling, Fraser, James, Kraaij, Robert, Hibbs, Matthew A., Gregson, Celia L., Paquette, Denis, Hofman, Albert, Wibom, Carl, Tranah, Gregory J., Marshall, Mhairi, Gardiner, Brooke B., Cremin, Katie, Auer, Paul, Hsu, Li, Ring, Sue, Tung, Joyce Y., Thorleifsson, Gudmar, Enneman, Anke W., van Schoor, Natasja M., de Groot, Lisette C. P. G. M., van der Velde, Nathalie, Melin, Beatrice, Kemp, John P., Christiansen, Claus, Sayers, Adrian, Zhou, Yanhua, Calderari, Sophie, van Rooij, Jeroen, Carlson, Chris, Peters, Ulrike, Berlivet, Soizik, Dostie, Josée, Uitterlinden, Andre G., Williams, Stephen R., Farber, Charles, Grinberg, Daniel, LaCroix, Andrea Z., Haessler, Jeff, Chasman, Daniel I., Giulianini, Franco, Rose, Lynda M., Ridker, Paul M., Eisman, John A., Nguyen, Tuan V., Center, Jacqueline R., Nogues, Xavier, Garcia-Giralt, Natalia, Launer, Lenore L., Gudnason, Vilmunder, Mellström, Dan, Vandenput, Liesbeth, Amin, Najaf, van Duijn, Cornelia M., Karlsson, Magnus K., Ljunggren, Östen, Svensson, Olle, Hallmans, Göran, Rousseau, François, Giroux, Sylvie, Bussière, Johanne, Arp, Pascal P., Koromani, Fjorda, Prince, Richard L., Lewis, Joshua R., Langdahl, Bente L., Hermann, Pernille A., Jensen, Jens-Erik B., Kaptoge, Stephen, Khaw, Kay-Tee, Reeve, Jonathan, Formosa, Melissa M., Xuereb-Anastasi, Angela, Åkesson, Kristina, McGuigan, Fiona E., Garg, Gaurav, Olmos, Jose M., Zarrabeitia, Maria T., Riancho, Jose A., Ralston, Stuart H., Alonso, Nerea, Jiang, Xi, Goltzman, David, Pastinen, Tomi, Grundberg, Elin, Gauguier, Dominique, Orwoll, Eric S., Karasik, David, Davey-Smith, George, Smith, Albert V., Siggeirsdottir, Kristin, Harris, Tamara B., Zillikens, Carola M., van Meurs, Joyce B. J., Thorsteinsdottir, Unnur, Maurano, Matthew T., Timpson, Nicholas J., Soranzo, Nicole, Durbin, Richard, Wilson, Scott G., Ntzani, Evangelia E., Brown, Matthew A., Stefansson, Kari, Hinds, David A., Spector, Tim, Cupples, Adrienne L., Ohlsson, Claes, Greenwood, Celia M. T., Jackson, Rebecca D., Rowe, David W., Loomis, Cynthia A., Evans, David M., Ackert-Bicknell, Cheryl L., Joyner, Alexandra L., Duncan, Emma L., Kiel, Douglas P., Rivadeneira, Fernando, and Richards, Brent J.

Published
2015
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12. Methylprednisolone in adults hospitalized with COVID-19 pneumonia

Author

Corral-Gudino, Luis, Bahamonde, Alberto, Arnaiz-Revillas, Francisco, Gómez-Barquero, Julia, Abadía-Otero, Jesica, García-Ibarbia, Carmen, Mora, Víctor, Cerezo-Hernández, Ana, Hernández, José L., López-Muñíz, Graciela, Hernández-Blanco, Fernando, Cifrián, Jose M., Olmos, Jose M., Carrascosa, Miguel, Nieto, Luis, Fariñas, María Carmen, and Riancho, José A.

Subjects
General Medicine
Published
2021
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14. GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia

Author

Corral-Gudino, Luis, Bahamonde, Alberto, Arnaiz-Revillas, Francisco, Gómez-Barquero, Julia, Abadía-Otero, Jesica, García-Ibarbia, Carmen, Mora, Víctor, Cerezo-Hernández, Ana, Hernández, José L., López-Muñíz, Graciela, Hernández-Blanco, Fernando, Cifrián, Jose M., Olmos, Jose M., Carrascosa, Miguel, Nieto, Luis, Fariñas, María Carmen, Riancho, José A., Buelta-González, Cristina, Marcos-Martínez, Luis A., Martínez-Vidal, Ana I., Dosantos-Gallego, Pilar R.l, Pérez-Sagredo, Jesús, Sandomingo-Freire, Silvia, Muñumer-Blázquez, Rebeca, Paredes-Mogollo, Antonio, Brague-Allegue, Elena, García-Rivero, Juan L., Olmos, José M., Fariñas, Carmen, Cifrian, José M., Hernández, Jose L., Mora, Victor, Nieto, Sara, Ruiz-Cubillán, Juan, Bermúdez, Arancha, Pardo, Javier, Amado, Carlos, Insunza, Andrés, Gil, Aritz, Diaz-Terán, Teresa, Fayos, Marina, Zabaleta, Miguel A., Parra, Juan J., Ruíz-de-Temiño-de-la-Peña, Angela, Arroyo-Domingo, C. Ainhoa, Mena-Martín, Javier, Miramontes-González, Pablo, Jiménez-Masa, Ana E, Pastor-Mancisidor, Luis, Álvaro-de-Castro, Tanía M, Pérez-Panizo, María Cruz, Ruíz-Albi, Tomás, de-la-Colina-Rojo, C Gema, Andrés-Calvo, María, Crespo-Sedano, Andrea, Morejón-Huerta, Begoña, Briongos-Figuero, Laisa S., Frutos-Arriba, Julio F, Pagán-Buzo, Javier, Gabella-Martín, Miriam, Cobos-Siles, Marta, and Gómez-García, Ana

Subjects
ARDS, medicine.medical_specialty, business.industry, medicine.disease, Intensive care unit, law.invention, Pneumonia, Randomized controlled trial, Methylprednisolone, law, Internal medicine, Relative risk, medicine, Breathing, Clinical endpoint, business, medicine.drug
Abstract

BackgroundWe aimed to determine whether a 6-day course of intravenous methylprednisolone (MP) improves outcome in patients with SARS CoV-2 infection at risk of developing Acute Respiratory Distress Syndrome (ARDS).MethodsMulticentric, partially randomized, preference, open-label trial, including adults with COVID-19 pneumonia, impaired gas exchange and biochemical evidence of hyper-inflammation. Patients were assigned to standard of care (SOC), or SOC plus intravenous MP [40mg/12h 3 days, then 20mg/12h 3 days]. The primary endpoint was a composite of death, admission to the intensive care unit (ICU) or requirement of non-invasive ventilation (NIV).ResultsWe analyzed 85 patients (34, randomized to MP; 22, assigned to MP by clinician’s preference; 29, control group). Patients’ age (mean 68±12 yr) was related to outcome. The use of MP was associated with a reduced risk of the composite endpoint in the intention-to-treat, age-stratified analysis (combined risk ratio -RR-0.55 [95% CI 0.33-0.91]; p=0.024). In the per-protocol analysis, RR was 0.11 (0.01-0.83) in patients aged 72 yr or less, 0.61 (0.32-1.17) in those over 72 yr, and 0.37 (0.19-0.74, p=0.0037) in the whole group after age-adjustment by stratification. The decrease in C-reactive protein levels was more pronounced in the MP group (p=0.0003). Hyperglycemia was more frequent in the MP group.ConclusionsA short course of MP had a beneficial effect on the clinical outcome of severe COVID-19 pneumonia, decreasing the risk of the composite end point of admission to ICU, NIV or death.

Published
2020
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15. Trend in hip fracture epidemiology over a 14-year period in a Spanish population

Author

Hernandez, Jose L., Olmos, Jose M., Alonso, Maria A., Gonzalez-Fernandez, Carmen R., Martinez, Josefina, Pajaron, Marcos, Llorca, Javier, and Gonzalez-Macias, Jesus

Subjects
Osteoporosis -- Case studies, Osteoporosis -- Causes of, Osteoporosis -- Diagnosis, Osteoporosis -- Care and treatment, Hip joint -- Fractures, Hip joint -- Causes of, Hip joint -- Care and treatment, Hip joint -- Risk factors, Health
Published
2006

17. Time course of bone loss in patients with anorexia nervosa

Author

Olmos, Jose M., Valero, Carmen, Gomez del Barrio, Andres, Amado, Jose A., Hernandez, Jose L., Menendez-Arango, Jose, and Gonzalez-Macias, Jesus

Subjects
Anorexia nervosa -- Demographic aspects, Anorexia nervosa -- Research, Anorexia nervosa -- Patient outcomes, Osteoporosis -- Risk factors, Osteoporosis -- Demographic aspects, Osteoporosis -- Research, Bones -- Density, Bones -- Measurement, Bones -- Research, Food/cooking/nutrition, Psychology and mental health
Published
2010

18. Assessment of gene-by-sex interaction effect on bone mineral density

Author

Liu, Ching-Ti Estrada, Karol Yerges-Armstrong, Laura M. and Amin, Najaf Evangelou, Evangelos Li, Guo Minster, Ryan L. and Carless, Melanie A. Kammerer, Candace M. Oei, Ling Zhou, Yanhua Alonso, Nerea Dailiana, Zoe Eriksson, Joel and Garcia-Giralt, Natalia Giroux, Sylvie Husted, Lise Bjerre and Khusainova, Rita I. Koromila, Theodora Kung, Annie WaiChee and Lewis, Joshua R. Masi, Laura Mencej-Bedrac, Simona Nogues, Xavier Patel, Millan S. Prezelj, Janez Richards, J. Brent and Sham, Pak Chung Spector, Timothy Vandenput, Liesbeth and Xiao, Su-Mei Zheng, Hou-Feng Zhu, Kun Balcells, Susana and Brandi, Maria Luisa Frost, Morten Goltzman, David and Gonzalez-Macias, Jesus Karlsson, Magnus Khusnutdinova, Elza K. and Kollia, Panagoula Langdahl, Bente Lomholt Ljunggren, Oesten and Lorentzon, Mattias Marc, Janja Mellstroem, Dan Ohlsson, Claes Olmos, Jose M. Ralston, Stuart H. Riancho, Jose A. and Rousseau, Francois Urreizti, Roser Van Hul, Wim Zarrabeitia, Maria T. Castano-Betancourt, Martha Demissie, Serkalem and Grundberg, Elin Herrera, Lizbeth Kwan, Tony Medina-Gomez, Carolina Pastinen, Tomi Sigurdsson, Gunnar Thorleifsson, Gudmar VanMeurs, Joyce B. J. Blangero, John Hofman, Albert and Liu, Yongmei Mitchell, Braxton D. O'Connell, Jeffrey R. and Oostra, Ben A. Rotter, Jerome I. Stefansson, Kari Streeten, Elizabeth A. Styrkarsdottir, Unnur Thorsteinsdottir, Unnur and Tylavsky, Frances A. Uitterlinden, Andre Cauley, Jane A. and Harris, Tamara B. Ioannidis, John P. A. Psaty, Bruce M. and Robbins, John A. Zillikens, M. Carola VanDuijn, Cornelia M. and Prince, Richard L. Karasik, David Rivadeneira, Fernando and Kiel, Douglas P. Cupples, L. Adrienne Hsu, Yi-Hsiang

Abstract

Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p?1?X?10-5) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect?=?0.02 and p?=?3.0?X?10-5; female effect?=?-0.007 and p?=?3.3?X?10-2), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p?

Published
2012

19. Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Author

Moayyeri, Alireza, Hsu, Yi-Hsiang, Karasik, David, Estrada, Karol, Xiao, Su-Mei, Nielson, Carrie, Srikanth, Priya, Giroux, Sylvie, Wilson, Scott G., Zheng, Hou-Feng, Smith, Albert V., Pye, Stephen R., Leo, Paul J., Teumer, Alexander, Hwang, Joo-Yeon, Ohlsson, Claes, McGuigan, Fiona, Minster, Ryan L., Hayward, Caroline, Olmos, Jose M., Lyytikaeinen, Leo-Pekka, Lewis, Joshua R., Swart, Karin M. A., Masi, Laura, Oldmeadow, Chris, Holliday, Elizabeth G., Cheng, Sulin, van Schoor, Natasja M., Harvey, Nicholas C., Kruk, Marcin, Fabiola Del Greco, M., Igl, Wilmar, Trummer, Olivia, Grigoriou, Efi, Luben, Robert, Liu, Ching-Ti, Zhou, Yanhua, Oei, Ling, Medina-Gomez, Carolina, Zmuda, Joseph, Tranah, Greg, Brown, Suzanne J., Williams, Frances M., Soranzo, Nicole, Jakobsdottir, Johanna, Siggeirsdottir, Kristin, Holliday, Kate L., Hannemann, Anke, Go, Min Jin, Garcia, Melissa, Polasek, Ozren, Laaksonen, Marika, Zhu, Kun, Enneman, Anke W., McEvoy, Mark, Peel, Roseanne, Sham, Pak Chung, Jaworski, Maciej, Johansson, Asa, Hicks, Andrew A., Pludowski, Pawel, Scott, Rodney, Dhonukshe-Rutten, Rosalie A. M., van der Velde, Nathalie, Kaehoenen, Mika, Viikari, Jorma S., Sievaenen, Harri, Raitakari, Olli T., Gonzalez-Macias, Jesus, Hernandez, Jose L., Mellstroem, Dan, Ljunggren, Östen, Cho, Yoon Shin, Voelker, Uwe, Nauck, Matthias, Homuth, Georg, Voelzke, Henry, Haring, Robin, Brown, Matthew A., McCloskey, Eugene, Nicholson, Geoffrey C., Eastell, Richard, Eisman, John A., Jones, Graeme, Reid, Ian R., Dennison, Elaine M., Wark, John, Boonen, Steven, Vanderschueren, Dirk, Wu, Frederick C. W., Aspelund, Thor, Richards, J. Brent, Bauer, Doug, Hofman, Albert, Khaw, Kay-Tee, Dedoussis, George, Obermayer-Pietsch, Barbara, Gyllensten, Ulf, Pramstaller, Peter P., Lorenc, Roman S., Cooper, Cyrus, Kung, Annie Wai Chee, Lips, Paul, Alen, Markku, Attia, John, Luisa Brandi, Maria, de Groot, Lisette C. P. G. M., Lehtimaeki, Terho, Riancho, Jose A., Campbell, Harry, Liu, Yongmei, Harris, Tamara B., Akesson, Kristina, Karlsson, Magnus, Lee, Jong-Young, Wallaschofski, Henri, Duncan, Emma L., O'Neill, Terence W., Gudnason, Vilmundur, Spector, Timothy D., Rousseau, Francois, Orwoll, Eric, Cummings, Steven R., Wareham, Nick J., Rivadeneira, Fernando, Uitterlinden, Andre G., Prince, Richard L., Kiel, Douglas P., Reeve, Jonathan, Kaptoge, Stephen K., Moayyeri, Alireza, Hsu, Yi-Hsiang, Karasik, David, Estrada, Karol, Xiao, Su-Mei, Nielson, Carrie, Srikanth, Priya, Giroux, Sylvie, Wilson, Scott G., Zheng, Hou-Feng, Smith, Albert V., Pye, Stephen R., Leo, Paul J., Teumer, Alexander, Hwang, Joo-Yeon, Ohlsson, Claes, McGuigan, Fiona, Minster, Ryan L., Hayward, Caroline, Olmos, Jose M., Lyytikaeinen, Leo-Pekka, Lewis, Joshua R., Swart, Karin M. A., Masi, Laura, Oldmeadow, Chris, Holliday, Elizabeth G., Cheng, Sulin, van Schoor, Natasja M., Harvey, Nicholas C., Kruk, Marcin, Fabiola Del Greco, M., Igl, Wilmar, Trummer, Olivia, Grigoriou, Efi, Luben, Robert, Liu, Ching-Ti, Zhou, Yanhua, Oei, Ling, Medina-Gomez, Carolina, Zmuda, Joseph, Tranah, Greg, Brown, Suzanne J., Williams, Frances M., Soranzo, Nicole, Jakobsdottir, Johanna, Siggeirsdottir, Kristin, Holliday, Kate L., Hannemann, Anke, Go, Min Jin, Garcia, Melissa, Polasek, Ozren, Laaksonen, Marika, Zhu, Kun, Enneman, Anke W., McEvoy, Mark, Peel, Roseanne, Sham, Pak Chung, Jaworski, Maciej, Johansson, Asa, Hicks, Andrew A., Pludowski, Pawel, Scott, Rodney, Dhonukshe-Rutten, Rosalie A. M., van der Velde, Nathalie, Kaehoenen, Mika, Viikari, Jorma S., Sievaenen, Harri, Raitakari, Olli T., Gonzalez-Macias, Jesus, Hernandez, Jose L., Mellstroem, Dan, Ljunggren, Östen, Cho, Yoon Shin, Voelker, Uwe, Nauck, Matthias, Homuth, Georg, Voelzke, Henry, Haring, Robin, Brown, Matthew A., McCloskey, Eugene, Nicholson, Geoffrey C., Eastell, Richard, Eisman, John A., Jones, Graeme, Reid, Ian R., Dennison, Elaine M., Wark, John, Boonen, Steven, Vanderschueren, Dirk, Wu, Frederick C. W., Aspelund, Thor, Richards, J. Brent, Bauer, Doug, Hofman, Albert, Khaw, Kay-Tee, Dedoussis, George, Obermayer-Pietsch, Barbara, Gyllensten, Ulf, Pramstaller, Peter P., Lorenc, Roman S., Cooper, Cyrus, Kung, Annie Wai Chee, Lips, Paul, Alen, Markku, Attia, John, Luisa Brandi, Maria, de Groot, Lisette C. P. G. M., Lehtimaeki, Terho, Riancho, Jose A., Campbell, Harry, Liu, Yongmei, Harris, Tamara B., Akesson, Kristina, Karlsson, Magnus, Lee, Jong-Young, Wallaschofski, Henri, Duncan, Emma L., O'Neill, Terence W., Gudnason, Vilmundur, Spector, Timothy D., Rousseau, Francois, Orwoll, Eric, Cummings, Steven R., Wareham, Nick J., Rivadeneira, Fernando, Uitterlinden, Andre G., Prince, Richard L., Kiel, Douglas P., Reeve, Jonathan, and Kaptoge, Stephen K.

Abstract

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

Published
2014
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21. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Author

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, Natalia, Giroux, Sylvie, Hallmans, Goran, 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, Gonzalez-Macias, Jesus, Kahonen, 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, Mellstrom, Dan, Obermayer-Pietsch, Barbara, Olmos, Jose M., Pettersson-Kymmer, Ulrika, Reid, David M., Riancho, Jose A., Ridker, Paul M., Rousseau, Francois, Slagboom, P. Eline, Tang, Nelson L. S., Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, Maria T., Aulchenko, Yurii S., Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gomez, Carolina, Palsson, Stefan Th, Reppe, Sjur, Rotter, Jerome I., Sigurdsson, Gunnar, van Meurs, Joyce B. J., Verlaan, Dominique, Williams, Frances M. K., Wood, Andrew R., Zhou, Yanhua, Gautvik, Kaare M., 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, Lehtimaki, 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, Andre G., Ralston, Stuart H., Ioannidis, John P. A., Kiel, Douglas P., Rivadeneira, Fernando, 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, Natalia, Giroux, Sylvie, Hallmans, Goran, 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, Gonzalez-Macias, Jesus, Kahonen, 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, Mellstrom, Dan, Obermayer-Pietsch, Barbara, Olmos, Jose M., Pettersson-Kymmer, Ulrika, Reid, David M., Riancho, Jose A., Ridker, Paul M., Rousseau, Francois, Slagboom, P. Eline, Tang, Nelson L. S., Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, Maria T., Aulchenko, Yurii S., Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gomez, Carolina, Palsson, Stefan Th, Reppe, Sjur, Rotter, Jerome I., Sigurdsson, Gunnar, van Meurs, Joyce B. J., Verlaan, Dominique, Williams, Frances M. K., Wood, Andrew R., Zhou, Yanhua, Gautvik, Kaare M., 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, Lehtimaki, 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, Andre G., Ralston, Stuart H., Ioannidis, John P. A., Kiel, Douglas P., and Rivadeneira, Fernando

Abstract

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 x 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 x 10(-4), Bonferroni corrected), of which six reached P < 5 x 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Published
2012
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24. Risk factors for prediction of inadequate response to antiresorptives

Author

Díez-Pérez, Adolfo, primary, Olmos, Jose M, additional, Nogués, Xavier, additional, Sosa, Manuel, additional, Díaz-Curiel, Manuel, additional, Pérez-Castrillón, Jose Luis, additional, Pérez-Cano, Ramon, additional, Muñoz-Torres, Manuel, additional, Torrijos, Antonio, additional, Jodar, Esteban, additional, Del Rio, Luis, additional, Caeiro-Rey, Jose R, additional, Farrerons, Jordi, additional, Vila, Joan, additional, Arnaud, Claude, additional, and González-Macías, Jesus, additional

Published
2012
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29. Amylin in the insulin resistance of patients with rheumatoid arthritis.

Author

Ferraz-Amaro I, López-Mejias R, Tejera-Segura B, de Vera-González AM, Ubilla B, Olmos JM, Hernández JL, and González-Gay MA

Subjects
Adult, Aged, Antirheumatic Agents therapeutic use, Apolipoprotein A-I metabolism, Apolipoproteins B metabolism, Arthritis, Rheumatoid drug therapy, C-Peptide metabolism, Case-Control Studies, Cholesterol, HDL metabolism, Cholesterol, LDL metabolism, Cross-Sectional Studies, Female, Humans, Insulin metabolism, Lipoprotein(a) metabolism, Male, Middle Aged, Multivariate Analysis, Rheumatoid Factor, Arthritis, Rheumatoid metabolism, Insulin Resistance, Islet Amyloid Polypeptide metabolism
Abstract

Objectives: Amylin, which is co-secreted with insulin, plays a role in glycemic regulation and is impaired in type 2 diabetes. In the present study we assess, for the first time, the implication of amylin in the development of insulin resistance (IR) in rheumatoid arthritis (RA)., Methods: This was a cross-sectional study involving 361 non-diabetic individuals, 151 patients with RA and 210 sex-matched controls. Insulin, C-peptide, amylin, lipoprotein serum concentrations, and IR indexes by homeostatic model assessment (HOMA2) were evaluated in patients and controls. A multivariable analysis, adjusted for IR-related factors, was performed to determine the differences between patients and controls vis-à-vis amylin and how it is related to IR in RA., Results: Insulin, C-peptide and HOMA2-IR indexes were higher in RA patients than in controls. Amylin serum levels were found to be upregulated in RA patients compared to controls (1.36 ± 0.81 vs. 1.79 ± 1.51 ng/ml, p=0.011), although this difference was lost after adjusting for covariates (p=0.46). While amylin positively correlated with the presence of rheumatoid factor (beta coef. 0.90 [95%CI -0.23-1.56], p=0.009) and SDAI (beta coef 0.01 [95%CI 0.00-0.03], p=0.034), no significant association with other disease activity scores, glucocorticoid intake, methotrexate use or TNF-alpha inhibitors was found., Conclusions: IR in RA does not appear to be mediated by amylin. This would imply that the mechanisms associated with IR in RA patients differ from those at work in type 2 diabetes.

Published
2018

30. Proprotein convertase subtilisin/kexin type 9 in rheumatoid arthritis.

Author

Ferraz-Amaro I, López-Mejías R, Ubilla B, Genre F, Tejera-Segura B, de Vera-González AM, González-Rivero AF, Olmos JM, Hernández JL, Llorca J, and González-Gay MA

Subjects
Aged, Arthritis, Rheumatoid complications, Arthritis, Rheumatoid diagnostic imaging, Carotid Artery Diseases complications, Carotid Artery Diseases diagnostic imaging, Carotid Intima-Media Thickness, Cross-Sectional Studies, Female, Humans, Lipids blood, Lipoproteins blood, Male, Middle Aged, Plaque, Atherosclerotic complications, Plaque, Atherosclerotic diagnostic imaging, Arthritis, Rheumatoid blood, Carotid Artery Diseases blood, Plaque, Atherosclerotic blood, Proprotein Convertase 9 blood, Up-Regulation
Abstract

Objectives: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked with cardiovascular risk. The purpose of the present study was to examine whether PCSK9 levels are related to both abnormalities in the lipid profile and the severe atherosclerosis that occur in rheumatoid arthritis (RA) patients., Methods: Cross-sectional study that encompassed 520 individuals; 326 patients with RA and 194 age- and sex-matched controls. PCSK9 and lipoproteins serum concentrations, standard lipid profile and carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients and controls. A multivariable analysis, adjusted for standard cardiovascular risk factors, was performed to evaluate the influence of PCSK9 on RA related dyslipidaemia and subclinical carotid atherosclerosis., Results: After adjusting for classical cardiovascular risk factors, lipid profile and statins, RA patients showed lower PCSK9 serum concentrations than controls (beta coefficient -45 95%CI [-53, -38] ng/ml, p=0.00). PCSK9 was associated with both cIMT and the presence of carotid plaques in RA patients. However, this association was lost after adjusting for classical cardiovascular risk factors., Conclusions: PCSK9 is down-regulated in patients with RA.

Published
2016

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