Search

Your search keyword '"Ohlsson C"' showing total 1,120 results
Start Over Author "Ohlsson C" Language english
1,120 results on '"Ohlsson C"'

1. WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M

Author

Henning P, Movérare-Skrtic S, Westerlund A, Souza PPC, Floriano-Marcelino T, Nilsson KH, El Shahawy M, Ohlsson C, and Lerner UH

Subjects
oncostatin m, wnt16, osteoclast, osteoblast, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Petra Henning,1 Sofia Movérare-Skrtic,1 Anna Westerlund,1 Pedro Paulo Chaves de Souza,2,3 Thais Floriano-Marcelino,3 Karin H Nilsson,1 Maha El Shahawy,1,4 Claes Ohlsson,1 Ulf H Lerner1 1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2The Innovation in Biomaterials Laboratory, School of Dentistry, Federal University of Goiás, Goiânia, Brazil; 3Department of Physiology and Pathology, São Paulo State University (UNESP), School of Dentistry, Araraquara, Brazil; 4Department of Oral Biology, Faculty of Dentistry, Minia University, Minia, 61511, EgyptCorrespondence: Ulf H LernerUniversity of Gothenburg, Klin Farm Lab, Vita Straket 11, Gothenburg, 41345, SwedenTel +46 70 651 91 03Email ulf.lerner@gu.seBackground: Bone loss is often observed adjacent to inflammatory processes. The WNT signaling pathways have been implicated as novel regulators of both immune responses and bone metabolism. WNT16 is important for cortical bone mass by inhibiting osteoclast differentiation, and we have here investigated the regulation of WNT16 by several members of the pro-inflammatory gp130 cytokine family.Methods: The expression and regulation of Wnt16 in primary murine cells were studied by qPCR, scRNAseq and in situ hybridization. Signaling pathways were studied by siRNA silencing. The importance of oncostatin M (OSM)-induced WNT16 expression for osteoclastogenesis was studied in cells from Wnt16-deficient and wild-type mice.Results: We found that IL-6/sIL-6R and OSM induce the expression of Wnt16 in primary mouse calvarial osteoblasts, with OSM being the most robust stimulator. The induction of Wnt16 by OSM was dependent on gp130 and OSM receptor (OSMR), and downstream signaling by the SHC1/STAT3 pathway, but independent of ERK. Stimulation of the calvarial cells with OSM resulted in enhanced numbers of mature, oversized osteoclasts when cells were isolated from Wnt16 deficient mice compared to cells from wild-type mice. OSM did not affect Wnt16 mRNA expression in bone marrow cell cultures, explained by the finding that Wnt16 and Osmr are expressed in distinctly different cells in bone marrow, nor was osteoclast differentiation different in OSM-stimulated bone marrow cell cultures isolated from Wnt16−/- or wild-type mice. Furthermore, we found that Wnt16 expression is substantially lower in cells from bone marrow compared to calvarial osteoblasts.Conclusion: These findings demonstrate that OSM is a robust stimulator of Wnt16 mRNA in calvarial osteoblasts and that WNT16 acts as a negative feedback regulator of OSM-induced osteoclast formation in the calvarial bone cells, but not in the bone marrow.Keywords: oncostatin M, WNT16, osteoclast, osteoblast

Published
2021

2. Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX

Author

Kanis, J.A., Johansson, H., McCloskey, E.V., Liu, E., Åkesson, K.E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, C., Bischoff-Ferrari, H.A., Biver, E., Bruyère, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S.R., da Silva, J.A.P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J.M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.-C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R.J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M.K., Khosla, S., Kiel, D.P., Koh, W.-P., Koromani, F., Kotowicz, M.A., Kröger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellström, D., Merlijn, T., Nordström, A., Nordström, P., O’Neill, T.W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E.S., Pasco, J.A., Rivadeneira, F., Schott, A.-M., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M.A., Szulc, P., Tamaki, J., Torgerson, D.J., van Schoor, N.M., van Staa, T.P., Vila, J., Wareham, N.J., Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Vandenput, L., Harvey, N.C., Lorentzon, M., and Leslie, W.D.

Published
2023
Full Text
View/download PDF

3. Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan

Author

Vandenput, L., Johansson, H., McCloskey, E. V., Liu, E., Åkesson, K. E., Anderson, F. A., Azagra, R., Bager, C. L., Beaudart, C., Bischoff-Ferrari, H. A., Biver, E., Bruyère, O., Cauley, J. A., Center, J. R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C. J., Cummings, S. R., da Silva, J. A. P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A. B., Eisman, J. A., Elders, P. J. M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.-C., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R. J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M. K., Khosla, S., Kiel, D. P., Koh, W.-P., Koromani, F., Kotowicz, M. A., Kröger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellström, D., Merlijn, T., Nordström, A., Nordström, P., O’Neill, T. W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E. S., Pasco, J. A., Rivadeneira, F., Schei, B., Schott, A.-M., Shiroma, E. J., Siggeirsdottir, K., Simonsick, E. M., Sornay-Rendu, E., Sund, R., Swart, K. M. A., Szulc, P., Tamaki, J., Torgerson, D. J., van Schoor, N. M., van Staa, T. P., Vila, J., Wareham, N. J., Wright, N. C., Yoshimura, N., Zillikens, M. C., Zwart, M., Harvey, N. C., Lorentzon, M., Leslie, W. D., and Kanis, J. A.

Published
2022
Full Text
View/download PDF

12. Update of the fracture risk prediction tool FRAX:a systematic review of potential cohorts and analysis plan

Author

Vandenput, L, Johansson, H, McCloskey, E V, Liu, E, Åkesson, K E, Anderson, F A, Azagra, R, Bager, C L, Beaudart, C, Bischoff-Ferrari, H A, Biver, E, Bruyère, O, Cauley, J A, Center, J R, Chapurlat, R, Christiansen, C, Cooper, C, Crandall, C J, Cummings, S R, da Silva, J A P, Dawson-Hughes, B, Diez-Perez, A, Dufour, A B, Eisman, J A, Elders, P J M, Ferrari, S, Fujita, Y, Fujiwara, S, Glüer, C-C, Goldshtein, I, Goltzman, D, Gudnason, V, Hall, J, Hans, D, Hoff, M, Hollick, R J, Huisman, M, Iki, M, Ish-Shalom, S, Jones, G, Karlsson, M K, Khosla, S, Kiel, D P, Koh, W-P, Koromani, F, Kotowicz, M A, Kröger, H, Kwok, T, Lamy, O, Langhammer, A, Larijani, B, Lippuner, K, Mellström, D, Merlijn, T, Nordström, A, Nordström, P, O'Neill, T W, Obermayer-Pietsch, B, Ohlsson, C, Orwoll, E S, Pasco, J A, Rivadeneira, F, Schei, B, Schott, A-M, Shiroma, E J, Siggeirsdottir, K, Simonsick, E M, Sornay-Rendu, E, Sund, R, Swart, K M A, Szulc, P, Tamaki, J, Torgerson, D J, van Schoor, N M, van Staa, T P, Vila, J, Wareham, N J, Wright, N C, Yoshimura, N, Zillikens, M C, Zwart, M, Harvey, N C, Lorentzon, M, Leslie, W D, and Kanis, J A

Subjects
SDG 3 - Good Health and Well-being, Bone Density, Hip Fractures, Risk Factors, Endocrinology, Diabetes and Metabolism, Humans, Osteoporosis, Prospective Studies, 610 Medicine & health, Risk Assessment, Osteoporotic Fractures
Abstract

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Published
2022

14. Update of the fracture risk prediction tool FRAX: A systematic review of potential cohorts and analysis plan

Author

Vandenput, Lisbeth, Johansson, H., McCloskey, E. V., Liu, E., Akesson, Kristina E., Anderson, F.A., Azagra, R., Bager, C.L., Beaudart, Charlotte, Bischoff-Ferrari, H.A., Biver, E., Bruyère, Olivier, Cauley, J.A., Center, J.R., Chapulat, R., Christiansen, C., Cooper, Cyrus, Crandall, Carolyn J., Cummings, Steven, da Silva, J.A.P., Dawson-Hughes, Bess, Diez-Pérez, A., Dufour, Alyssa B., Eisman, J.A., Elders, Petra J.M., Ferrari, S., Fujita, Y., Fujiwara, S., Glüer, C.C., Goldstein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, Rosemary J., Huisman, Martijn, Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M.K., Khosla, Sundeep, Kiel, D.P., Koh, W-P, Koromani, F., Kotowicz, M.A., Kroger, H., Kwok, T., Lamy, Olivier, Langhammer, Arnulf, Larijani, Bagher, Lippuner, Kurt, Mellström, D, Merlijn, Thomas, Nordstrom, A., Nordstrom, P., O'Neill, T.W., Obermayer-Piestch, B., Harvey, Nicholas, Kanis, J A., Ohlsson, C., Orwoll, E.S., Pasco, J.A., Rivadeneira, F., Schei, B., Schott, A.M., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K.M.A., Szulc, P., Tamaki, J., Torgerson, D.J., Van Schoor, N.M., van Staa, T.P., Vilas, J.C., Wareham, N.J, Wright, N.C., Yoshimura, N., Zillikens, M.C., Zwart, M., Lorentzon, M., and Leslie, W.D.

Abstract

Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Published
2022

16. Role of the microbiome in regulating bone metabolism and susceptibility to osteoporosis

Author

Cronin, O., Lanham-New, S.A., Corfe, B.M., Gregson, C.L., Darling, A.L., Ahmadi, K.R., Gibson, P.S., Tobias, J.H., Ward, K.A., Traka, M.H., Rossi, M., Williams, C., Harvey, N.C., Cooper, C., Whelan, K., Uitterlinden, A.G., O’Toole, P.W., Ohlsson, C., Compston, J.E., and Ralston, S.H.

Abstract

The human microbiota functions at the interface between diet, medication-use, lifestyle, host immune development and health. It is therefore closely aligned with many of the recognised modifiable factors that influence bone mass accrual in the young, and bone maintenance and skeletal decline in older populations. While understanding of the relationship between micro-organisms and bone health is still in its infancy, two decades of broader microbiome research and discovery supports a role of the human gut microbiome in the regulation of bone metabolism and pathogenesis of osteoporosis as well as its prevention and treatment. Pre-clinical research has demonstrated biological interactions between the microbiome and bone metabolism. Furthermore, observational studies and randomized clinical trials have indicated that therapeutic manipulation of the microbiota by oral administration of probiotics may influence bone turnover and prevent bone loss in humans. In this paper, we summarize the content, discussion and conclusions of a workshop held by the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society in October, 2020. We provide a detailed review of the literature examining the relationship between the microbiota and bone health in animal models and in humans, as well as formulating the agenda for key research priorities required to advance this field. We also underscore the potential pitfalls in this research field that should be avoided and provide methodological recommendations to facilitate bridging the gap from promising concept to a potential cause and intervention target for osteoporosis.

Published
2022

18. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Author

Cornelis, M C, Byrne, E M, Esko, T, Nalls, M A, Ganna, A, Paynter, N, Monda, K L, Amin, N, Fischer, K, Renstrom, F, Ngwa, J S, Huikari, V, Cavadino, A, Nolte, I M, Teumer, A, Yu, K, Marques-Vidal, P, Rawal, R, Manichaikul, A, Wojczynski, M K, Vink, J M, Zhao, J H, Burlutsky, G, Lahti, J, Mikkilä, V, Lemaitre, R N, Eriksson, J, Musani, S K, Tanaka, T, Geller, F, Luan, J, Hui, J, Mägi, R, Dimitriou, M, Garcia, M E, Ho, W-K, Wright, M J, Rose, L M, Magnusson, P K E, Pedersen, N L, Couper, D, Oostra, B A, Hofman, A, Ikram, M A, Tiemeier, H W, Uitterlinden, A G, van Rooij, F J A, Barroso, I, Johansson, I, Xue, L, Kaakinen, M, Milani, L, Power, C, Snieder, H, Stolk, R P, Baumeister, S E, Biffar, R, Gu, F, Bastardot, F, Kutalik, Z, Jacobs, Jr, D R, Forouhi, N G, Mihailov, E, Lind, L, Lindgren, C, Michaëlsson, K, Morris, A, Jensen, M, Khaw, K-T, Luben, R N, Wang, J J, Männistö, S, Perälä, M-M, Kähönen, M, Lehtimäki, T, Viikari, J, Mozaffarian, D, Mukamal, K, Psaty, B M, Döring, A, Heath, A C, Montgomery, G W, Dahmen, N, Carithers, T, Tucker, K L, Ferrucci, L, Boyd, H A, Melbye, M, Treur, J L, Mellström, D, Hottenga, J J, Prokopenko, I, Tönjes, A, Deloukas, P, Kanoni, S, Lorentzon, M, Houston, D K, Liu, Y, Danesh, J, Rasheed, A, Mason, M A, Zonderman, A B, Franke, L, Kristal, B S, Karjalainen, J, Reed, D R, Westra, H-J, Evans, M K, Saleheen, D, Harris, T B, Dedoussis, G, Curhan, G, Stumvoll, M, Beilby, J, Pasquale, L R, Feenstra, B, Bandinelli, S, Ordovas, J M, Chan, A T, Peters, U, Ohlsson, C, Gieger, C, Martin, N G, Waldenberger, M, Siscovick, D S, Raitakari, O, Eriksson, J G, Mitchell, P, Hunter, D J, Kraft, P, Rimm, E B, Boomsma, D I, Borecki, I B, Loos, R J F, Wareham, N J, Vollenweider, P, Caporaso, N, Grabe, H J, Neuhouser, M L, Wolffenbuttel, B H R, Hu, F B, Hyppönen, E, Järvelin, M-R, Cupples, L A, Franks, P W, Ridker, P M, van Duijn, C M, Heiss, G, Metspalu, A, North, K E, Ingelsson, E, Nettleton, J A, van Dam, R M, and Chasman, D I

Published
2015
Full Text
View/download PDF

24. Sarcopenia definitions as predictors of fracture risk independent of FRAX®, falls, and BMD in the osteoporotic fractures in men (MrOS) study: a meta‐analysis

Author

Harvey, N.C., Orwoll, E., Kwok, T., Karlsson, M.K., Rosengren, B.E., Ribom, E., Cauley, J.A., Cawthon, P.M., Ensrud, K., Liu, E., Cruz-Jentoft, A.J., Fielding, R.A., Cooper, C., Kanis, J.A., Lorentzon, M., Ohlsson, C., Mellström, D., Johansson, H., and McCloskey, E.

Subjects
musculoskeletal system, human activities
Abstract

Dual‐energy X‐ray absorptiometry (DXA)‐derived appendicular lean mass/height2 (ALM/ht2) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX‐MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T‐score. Results were synthesized by meta‐analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T‐score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures.

Published
2021

28. Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Author

Ahluwalia, T.S., Prins, B.P., Abdollahi, M., Armstrong, N.J., Aslibekyan, S., Bain, L., Jefferis, B., Baumert, J., Beekman, M., Ben-Shlomo, Y., Bis, J.C., Mitchell, B.D., Geus, E. de, Delgado, G.E., Marek, D., Eriksson, J., Kajantie, E., Kanoni, S., Kemp, J.P., Lu, C., Marioni, R.E., McLachlan, S., Milaneschi, Y., Nolte, I.M., Petrelis, A.M., Porcu, E., Sabater-Lleal, M., Naderi, E., Seppala, I., Shah, T., Singhal, G., Standl, M., Teumer, A., Thalamuthu, A., Thiering, E., Trompet, S., Ballantyne, C.M., Benjamin, E.J., Casas, J.P., Toben, C., Dedoussis, G., Deelen, J., Durda, P., Engmann, J., Feitosa, M.F., Grallert, H., Hammarstedt, A., Harris, S.E., Homuth, G., Hottenga, J.J., Jalkanen, S., Jamshidi, Y., Jawahar, M.C., Jess, T., Kivimaki, M., Kleber, M.E., Lahti, J., Liu, Y., Marques-Vidal, P., Mellstrom, D., Mooijaart, S.P., Muller-Nurasyid, M., Penninx, B., Revez, J.A., Rossing, P., Raikkonen, K., Sattar, N., Scharnagl, H., Sennblad, B., Silveira, A., St Pourcain, B., Timpson, N.J., Trollor, J., Dongen, J. van, Heemst, D. van, Visvikis-Siest, S., Vollenweider, P., Volker, U., Waldenberger, M., Willemsen, G., Zabaneh, D., Morris, R.W., Arnett, D.K., Baune, B.T., Boomsma, D.I., Chang, Y.P.C., Deary, I.J., Deloukas, P., Eriksson, J.G., Evans, D.M., Ferreira, M.A., Gaunt, T., Gudnason, V., Hamsten, A., Heinrich, J., Hingorani, A., Humphries, S.E., Jukema, J.W., Koenig, W., Kumari, M., Kutalik, Z., Lawlor, D.A., Lehtimaki, T., Marz, W., Mather, K.A., Naitza, S., Nauck, M., Ohlsson, C., Price, J.F., Raitakari, O., Rice, K., Sachdev, P.S., Slagboom, E., Sorensen, T.I.A., Spector, T., Stacey, D., Stathopoulou, M.G., Tanaka, T., Wannamethee, S.G., Whincup, P., Rotter, J.I., Dehghan, A., Boerwinkle, E., Psaty, B.M., Snieder, H., Alizadeh, B.Z., and CHARGE Inflammation Working Grp

Abstract

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Published
2021

29. Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci

Author

Ahluwalia, TS, Prins, BP, Abdollahi, M, Armstrong, NJ, Aslibekyan, S, Bain, L, Jefferis, B, Baumert, J, Beekman, M, Ben-Shlomo, Y, Bis, JC, Mitchell, BD, de Geus, E, Delgado, GE, Marek, D, Eriksson, J, Kajantie, E, Kanoni, S, Kemp, JP, Lu, C, Marioni, RE, McLachlan, S, Milaneschi, Y, Nolte, IM, Petrelis, AM, Porcu, E, Sabater-Lleal, M, Naderi, E, Seppälä, I, Shah, T, Singhal, G, Standl, M, Teumer, A, Thalamuthu, A, Thiering, E, Trompet, S, Ballantyne, CM, Benjamin, EJ, Casas, JP, Toben, C, Dedoussis, G, Deelen, J, Durda, P, Engmann, J, Feitosa, MF, Grallert, H, Hammarstedt, A, Harris, SE, Homuth, G, Hottenga, J-J, Jalkanen, S, Jamshidi, Y, Jawahar, MC, Jess, T, Kivimaki, M, Kleber, ME, Lahti, J, Liu, Y, Marques-Vidal, P, Mellström, D, Mooijaart, SP, Müller-Nurasyid, M, Penninx, B, Revez, JA, Rossing, P, Räikkönen, K, Sattar, N, Scharnagl, H, Sennblad, B, Silveira, A, Pourcain, BS, Timpson, NJ, Trollor, J, CHARGE Inflammation Working Group, van Dongen, J, Van Heemst, D, Visvikis-Siest, S, Vollenweider, P, Völker, U, Waldenberger, M, Willemsen, G, Zabaneh, D, Morris, RW, Arnett, DK, Baune, BT, Boomsma, DI, Chang, Y-PC, Deary, IJ, Deloukas, P, Eriksson, JG, Evans, DM, Ferreira, MA, Gaunt, T, Gudnason, V, Hamsten, A, Heinrich, J, Hingorani, A, Humphries, SE, Jukema, JW, Koeing, W, Kumari, M, Kutalik, Z, Lawlor, DA, Lehtimäki, T, März, W, Mather, K, Naitza, S, Nauck, M, Ohlsson, C, Price, JF, Raitakari, O, Rice, K, Sachdev, PS, Slagboom, E, Sørensen, TIA, Spector, T, Stacey, D, Stathopoulou, MG, Tanaka, T, Wannamethee, SG, Whincup, P, Rotter, JI, Dehghan, A, Boerwinkle, E, Psaty, BM, Snieder, H, and Alizadeh, BZ

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery, and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed-effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on Chromosome (Chr) 2q14, (pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Published
2021

32. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author

Iurilli, M.L.C. Zhou, B. Bennett, J.E. Carrillo-Larco, R.M. Sophiea, M.K. Rodriguez-Martinez, A. Bixby, H. Solomon, B.D. Taddei, C. Danaei, G. Di Cesare, M. Stevens, G.A. Riley, L.M. Savin, S. Cowan, M.J. Bovet, P. Damasceno, A. Chirita-Emandi, A. Hayes, A.J. Ikeda, N. Jackson, R.T. Khang, Y.-H. Laxmaiah, A. Liu, J. Miranda, J.J. Saidi, O. Sebert, S. Sorić, M. Starc, G. Gregg, E.W. Abarca-Gómez, L. Abdeen, Z.A. Abdrakhmanova, S. Ghaffar, S.A. Rahim, H.F.A. Abu-Rmeileh, N.M. Garba, J.A. Acosta-Cazares, B. Adams, R.J. Aekplakorn, W. Afsana, K. Afzal, S. Agdeppa, I.A. Aghazadeh-Attari, J. Aguilar-Salinas, C.A. Agyemang, C. Ahmad, M.H. Ahmad, N.A. Ahmadi, A. Ahmadi, N. Ahmed, S.H. Ahrens, W. Aitmurzaeva, G. Ajlouni, K. Al-Hazzaa, H.M. Al-Lahou, B. Al-Raddadi, R. Alarouj, M. AlBuhairan, F. AlDhukair, S. Ali, M.M. Alkandari, A. Alkerwi, A. Allin, K. Alvarez-Pedrerol, M. Aly, E. Amarapurkar, D.N. Amiri, P. Amougou, N. Amouyel, P. Andersen, L.B. Anderssen, S.A. Ängquist, L. Anjana, R.M. Ansari-Moghaddam, A. Aounallah-Skhiri, H. Araújo, J. Ariansen, I. Aris, T. Arku, R.E. Arlappa, N. Aryal, K.K. Aspelund, T. Assah, F.K. Assunção, M.C.F. Aung, M.S. Auvinen, J. Mária Avdicová Avi, S. Azevedo, A. Azimi-Nezhad, M. Azizi, F. Azmin, M. Babu, B.V. Bæksgaard Jørgensen, M. Baharudin, A. Bahijri, S. Baker, J.L. Balakrishna, N. Bamoshmoosh, M. Banach, M. Bandosz, P. Banegas, J.R. Baran, J. Barbagallo, C.M. Barceló, A. Barkat, A. Barros, A.J.D. Barros, M.V.G. Basit, A. Bastos, J.L.D. Bata, I. Batieha, A.M. Batista, R.L. Battakova, Z. Batyrbek, A. Baur, L.A. Beaglehole, R. Bel-Serrat, S. Belavendra, A. Romdhane, H.B. Benedics, J. Benet, M. Bergh, I.H. Berkinbayev, S. Bernabe-Ortiz, A. Bernotiene, G. Bettiol, H. Bezerra, J. Bhagyalaxmi, A. Bharadwaj, S. Bhargava, S.K. Bhutta, Z.A. Bi, H. Bi, Y. Bia, D. Lele, E.C.B. Bikbov, M.M. Bista, B. Bjelica, D.J. Bjerregaard, P. Bjertness, E. Bjertness, M.B. Björkelund, C. Bloch, K.V. Blokstra, A. Bo, S. Bobak, M. Boddy, L.M. Boehm, B.O. Boeing, H. Boggia, J.G. Bogova, E. Boissonnet, C.P. Bojesen, S.E. Bonaccio, M. Bongard, V. Bonilla-Vargas, A. Bopp, M. Borghs, H. Braeckevelt, L. Braeckman, L. Bragt, M.C.E. Brajkovich, I. Branca, F. Breckenkamp, J. Breda, J. Brenner, H. Brewster, L.M. Brian, G.R. Brinduse, L. Brophy, S. Bruno, G. Bueno-de-Mesquita, H.B. Bugge, A. Buoncristiano, M. Burazeri, G. Burns, C. de León, A.C. Cacciottolo, J. Cai, H. Cama, T. Cameron, C. Camolas, J. Can, G. Candido, A.P.C. Cañete, F. Capanzana, M.V. Capková, N. Capuano, E. Capuano, V. Cardol, M. Cardoso, V.C. Carlsson, A.C. Carmuega, E. Carvalho, J. Casajús, J.A. Casanueva, F.F. Celikcan, E. Censi, L. Cervantes-Loaiza, M. Cesar, J.A. Chamukuttan, S. Chan, A.W. Chan, Q. Chaturvedi, H.K. Chaturvedi, N. Rahim, N.C.A. Chee, M.L. Chen, C.-J. Chen, F. Chen, H. Chen, S. Chen, Z. Cheng, C.-Y. Cheraghian, B. Chetrit, A. Chikova-Iscener, E. Chiolero, A. Chiou, S.-T. Chirlaque, M.-D. Cho, B. Christensen, K. Christofaro, D.G. Chudek, J. Cifkova, R. Cilia, M. Cinteza, E. Claessens, F. Clarke, J. Clays, E. Cohen, E. Concin, H. Confortin, S.C. Cooper, C. Coppinger, T.C. Corpeleijn, E. Costanzo, S. Cottel, D. Cowell, C. Craig, C.L. Crampin, A.C. Crujeiras, A.B. Csilla, S. Cucu, A.M. Cui, L. Cureau, F.V. Czenczek-Lewandowska, E. D’Arrigo, G. d’Orsi, E. Dacica, L. Dal Re Saavedra, M.A. Dallongeville, J. Damsgaard, C.T. Dankner, R. Dantoft, T.M. Dasgupta, P. Dastgiri, S. Dauchet, L. Davletov, K. De Backer, G. De Bacquer, D. de Gaetano, G. De Henauw, S. de Oliveira, P.D. De Ridder, D. De Ridder, K. de Rooij, S.R. De Smedt, D. Deepa, M. Deev, A.D. DeGennaro, V., Jr Dehghan, A. Delisle, H. Delpeuch, F. Demarest, S. Dennison, E. Dereń, K. Deschamps, V. Dhimal, M. Di Castelnuovo, A.F. Dias-da-Costa, J.S. Díaz-Sánchez, M.E. Diaz, A. Dika, Z. Djalalinia, S. Djordjic, V. Do, H.T.P. Dobson, A.J. Donati, M.B. Donfrancesco, C. Donoso, S.P. Döring, A. Dorobantu, M. Dorosty, A.R. Doua, K. Dragano, N. Drygas, W. Duan, J.L. Duante, C.A. Duboz, P. Duda, R.B. Duleva, V. Dulskiene, V. Dumith, S.C. Dushpanova, A. Dzerve, V. Dziankowska-Zaborszczyk, E. Eddie, R. Eftekhar, E. Egbagbe, E.E. Eggertsen, R. Eghtesad, S. Eiben, G. Ekelund, U. El-Khateeb, M. Ati, J.E. Eldemire-Shearer, D. Eliasen, M. Elliott, P. Engle-Stone, R. Enguerran, M. Erasmus, R.T. Erbel, R. Erem, C. Eriksen, L. Eriksson, J.G. Escobedo-de la Peña, J. Eslami, S. Esmaeili, A. Evans, A. Faeh, D. Fakhretdinova, A.A. Fall, C.H. Faramarzi, E. Farjam, M. Sant’Angelo, V.F. Farzadfar, F. Fattahi, M.R. Fawwad, A. Felix-Redondo, F.J. Ferguson, T.S. Fernandes, R.A. Fernández-Bergés, D. Ferrante, D. Ferrao, T. Ferrari, M. Ferrario, M.M. Ferreccio, C. Ferrer, E. Ferrieres, J. Figueiró, T.H. Fijalkowska, A. Fink, G. Fischer, K. Foo, L.H. Forsner, M. Fouad, H.M. Francis, D.K. Maria do Carmo Franco Frikke-Schmidt, R. Frontera, G. Fuchs, F.D. Fuchs, S.C. Fujiati, I.I. Fujita, Y. Fumihiko, M. Furusawa, T. Gaciong, Z. Gafencu, M. Galbarczyk, A. Galenkamp, H. Galeone, D. Galfo, M. Galvano, F. Gao, J. Garcia-de-la-Hera, M. García-Solano, M. Gareta, D. Garnett, S.P. Gaspoz, J.-M. Gasull, M. Gaya, A.C.A. Gaya, A.R. Gazzinelli, A. Gehring, U. Geiger, H. Geleijnse, J.M. Ghanbari, A. Ghasemi, E. Gheorghe-Fronea, O.-F. Giampaoli, S. Gianfagna, F. Gill, T.K. Giovannelli, J. Gironella, G. Giwercman, A. Gkiouras, K. Godos, J. Gogen, S. Goldberg, M. Goldsmith, R.A. Goltzman, D. Gómez, S.F. Gomula, A. da Silva, B.G.C. Gonçalves, H. Gonzalez-Chica, D.A. Gonzalez-Gross, M. González-Leon, M. González-Rivas, J.P. González-Villalpando, C. González-Villalpando, M.-E. Gonzalez, A.R. Gottrand, F. Graça, A.P. Graff-Iversen, S. Grafnetter, D. Grajda, A. Grammatikopoulou, M.G. Gregor, R.D. Grodzicki, T. Grøholt, E.K. Grøntved, A. Grosso, G. Gruden, G. Gu, D. Gualdi-Russo, E. Guallar-Castillón, P. Gualtieri, A. Gudmundsson, E.F. Gudnason, V. Guerrero, R. Guessous, I. Guimaraes, A.L. Gulliford, M.C. Gunnlaugsdottir, J. Gunter, M.J. Guo, X.-H. Guo, Y. Gupta, P.C. Gupta, R. Gureje, O. Gurzkowska, B. Gutiérrez-González, E. Gutierrez, L. Gutzwiller, F. Ha, S. Hadaegh, F. Hadjigeorgiou, C.A. Haghshenas, R. Hakimi, H. Halkjær, J. Hambleton, I.R. Hamzeh, B. Hange, D. Hanif, A.A.M. Hantunen, S. Hao, J. Kumar, R.H. Hashemi-Shahri, S.M. Hassapidou, M. Hata, J. Haugsgjerd, T. He, J. He, Y. He, Y. Heidinger-Felso, R. Heinen, M. Hejgaard, T. Hendriks, M.E. dos Santos Henrique, R. Henriques, A. Cadena, L.H. Herrala, S. Herrera, V.M. Herter-Aeberli, I. Heshmat, R. Hill, A.G. Ho, S.Y. Ho, S.C. Hobbs, M. Holdsworth, M. Homayounfar, R. Homs, C. Hopman, W.M. Horimoto, A.R.V.R. Hormiga, C.M. Horta, B.L. Houti, L. Howitt, C. Htay, T.T. Htet, A.S. Htike, M.M.T. Hu, Y. Huerta, J.M. Huhtaniemi, I.T. Huiart, L. Petrescu, C.H. Huisman, M. Husseini, A. Huu, C.N. Huybrechts, I. Hwalla, N. Hyska, J. Iacoviello, L. Ibarluzea, J.M. Ibrahim, M.M. Wong, N.I. Ikram, M.A. Iotova, V. Irazola, V.E. Ishida, T. Islam, M. Islam, S.M.S. Iwasaki, M. Jacobs, J.M. Jaddou, H.Y. Jafar, T. James, K. Jamil, K.M. Jamrozik, K. Janszky, I. Janus, E. Jarani, J. Jarvelin, M.-R. Jasienska, G. Jelakovic, A. Jelakovic, B. Jennings, G. Jha, A.K. Jiang, C.Q. Jimenez, R.O. Jöckel, K.-H. Joffres, M. Johansson, M. Jokelainen, J.J. Jonas, J.B. Jonnagaddala, J. Jørgensen, T. Joshi, P. Joukar, F. Jovic, D.P. Jóźwiak, J.J. Juolevi, A. Jurak, G. Simina, I.J. Juresa, V. Kaaks, R. Kaducu, F.O. Kafatos, A. Kajantie, E.O. Kalmatayeva, Z. Kalter-Leibovici, O. Kameli, Y. Kampmann, F.B. Kanala, K.R. Kannan, S. Kapantais, E. Karakosta, A. Kårhus, L.L. Karki, K.B. Katibeh, M. Katz, J. Katzmarzyk, P.T. Kauhanen, J. Kaur, P. Kavousi, M. Kazakbaeva, G.M. Keil, U. Boker, L.K. Keinänen-Kiukaanniemi, S. Kelishadi, R. Kelleher, C. Kemper, H.C.G. Kengne, A.P. Keramati, M. Kerimkulova, A. Kersting, M. Key, T. Khader, Y.S. Khalili, D. Khaw, K.-T. Kheiri, B. Kheradmand, M. Khosravi, A. Khouw, I.M.S.L. Kiechl-Kohlendorfer, U. Kiechl, S. Killewo, J. Kim, D.W. Kim, H.C. Kim, J. Kindblom, J.M. Klakk, H. Klimek, M. Klimont, J. Klumbiene, J. Knoflach, M. Koirala, B. Kolle, E. Kolsteren, P. König, J. Korpelainen, R. Korrovits, P. Korzycka, M. Kos, J. Koskinen, S. Kouda, K. Kovacs, V.A. Kowlessur, S. Koziel, S. Kratenova, J. Kratzer, W. Kriemler, S. Kristensen, P.L. Krokstad, S. Kromhout, D. Kruger, H.S. Kubinova, R. Kuciene, R. Kujala, U.M. Kujundzic, E. Kulaga, Z. Kumar, R.K. Kunešová, M. Kurjata, P. Kusuma, Y.S. Kuulasmaa, K. Kyobutungi, C. La, Q.N. Laamiri, F.Z. Laatikainen, T. Lachat, C. Laid, Y. Lam, T.H. Lambrinou, C.-P. Landais, E. Lanska, V. Lappas, G. Larijani, B. Latt, T.S. Lauria, L. Lazo-Porras, M. Le Coroller, G. Bao, K.L.N. Le Port, A. Le, T.D. Lee, J. Lee, J. Lee, P.H. Lehmann, N. Lehtimäki, T. Lemogoum, D. Levitt, N.S. Li, Y. Liivak, M. Lilly, C.L. Lim, W.-Y. Lima-Costa, M.F. Lin, H.-H. Lin, X. Lin, Y.-T. Lind, L. Linneberg, A. Lissner, L. Litwin, M. Liu, L. Lo, W.-C. Loit, H.-M. Long, K.Q. Lopes, L. Lopes, O. Lopez-Garcia, E. Lopez, T. Lotufo, P.A. Lozano, J.E. Lukrafka, J.L. Luksiene, D. Lundqvist, A. Lundqvist, R. Lunet, N. Lunogelo, C. Lustigová, M. Łuszczki, E. Ma, G. Ma, J. Ma, X. Machado-Coelho, G.L.L. Machado-Rodrigues, A.M. Macieira, L.M. Madar, A.A. Maggi, S. Magliano, D.J. Magnacca, S. Magriplis, E. Mahasampath, G. Maire, B. Majer, M. Makdisse, M. Mäki, P. Malekzadeh, F. Malekzadeh, R. Malhotra, R. Rao, K.M. Malyutina, S.K. Maniego, L.V. Manios, Y. Mann, J.I. Mansour-Ghanaei, F. Manzato, E. Margozzini, P. Markaki, A. Markey, O. Ioannidou, E.M. Marques-Vidal, P. Marques, L.P. Marrugat, J. Martin-Prevel, Y. Martin, R. Martorell, R. Martos, E. Maruszczak, K. Marventano, S. Mascarenhas, L.P. Masoodi, S.R. Mathiesen, E.B. Mathur, P. Matijasevich, A. Matsha, T.E. Mavrogianni, C. Mazur, A. Mbanya, J.C.N. McFarlane, S.R. McGarvey, S.T. McKee, M. McLachlan, S. McLean, R.M. McLean, S.B. McNulty, B.A. Benchekor, S.M. Medzioniene, J. Mehdipour, P. Mehlig, K. Mehrparvar, A.H. Meirhaeghe, A. Meisfjord, J. Meisinger, C. Menezes, A.M.B. Menon, G.R. Mensink, G.B.M. Menzano, M.T. Mereke, A. Meshram, I.I. Metspalu, A. Meyer, H.E. Mi, J. Michaelsen, K.F. Michels, N. Mikkel, K. Milkowska, K. Miller, J.C. Minderico, C.S. Mini, G.K. Miquel, J.F. Mirjalili, M.R. Mirkopoulou, D. Mirrakhimov, E. Mišigoj-Durakovic, M. Mistretta, A. Mocanu, V. Modesti, P.A. Moghaddam, S.S. Mohajer, B. Mohamed, M.K. Mohamed, S.F. Mohammad, K. Mohammadi, Z. Mohammadifard, N. Mohammadpourhodki, R. Mohan, V. Mohanna, S. Yusoff, M.F.M. Mohebbi, I. Mohebi, F. Moitry, M. Molbo, D. Møllehave, L.T. Møller, N.C. Molnár, D. Momenan, A. Mondo, C.K. Monroy-Valle, M. Monterrubio-Flores, E. Monyeki, K.D.K. Moon, J.S. Moosazadeh, M. Moreira, L.B. Morejon, A. Moreno, L.A. Morgan, K. Morin, S.N. Mortensen, E.L. Moschonis, G. Mossakowska, M. Mostafa, A. Mota-Pinto, A. Mota, J. Motlagh, M.E. Motta, J. Moura-dos-Santos, M.A. Mridha, M.K. Msyamboza, K.P. Mu, T.T. Muc, M. Mugoša, B. Muiesan, M.L. Mukhtorova, P. Müller-Nurasyid, M. Murphy, N. Mursu, J. Murtagh, E.M. Musa, K.I. Milanovic, S.M. Musil, V. Mustafa, N. Nabipour, I. Naderimagham, S. Nagel, G. Naidu, B.M. Najafi, F. Nakamura, H. Námešná, J. Nang, E.E.K. Nangia, V.B. Nankap, M. Narake, S. Nardone, P. Nauck, M. Neal, W.A. Nejatizadeh, A. Nekkantti, C. Nelis, K. Nelis, L. Nenko, I. Neovius, M. Nervi, F. Nguyen, C.T. Nguyen, N.D. Nguyen, Q.N. Nieto-Martínez, R.E. Nikitin, Y.P. Ning, G. Ninomiya, T. Nishtar, S. Noale, M. Noboa, O.A. Nogueira, H. Norat, T. Nordendahl, M. Nordestgaard, B.G. Noto, D. Nowak-Szczepanska, N. Al Nsour, M. Nuhoglu, I. Nurk, E. O’Neill, T.W. O’Reilly, D. Obreja, G. Ochimana, C. Ochoa-Avilés, A.M. Oda, E. Oh, K. Ohara, K. Ohlsson, C. Ohtsuka, R. Olafsson, O. Olinto, M.T.A. Oliveira, I.O. Omar, M.A. Onat, A. Ong, S.K. Ono, L.M. Ordunez, P. Ornelas, R. Ortiz, A.P. Ortiz, P.J. Osler, M. Osmond, C. Ostojic, S.M. Ostovar, A. Otero, J.A. Overvad, K. Owusu-Dabo, E. Paccaud, F.M. Padez, C. Pagkalos, I. Pahomova, E. de Paiva, K.M. Pajak, A. Palli, D. Palloni, A. Palmieri, L. Pan, W.-H. Panda-Jonas, S. Pandey, A. Panza, F. Papandreou, D. Park, S.-W. Park, S. Parnell, W.R. Parsaeian, M. Pascanu, I.M. Pasquet, P. Patel, N.D. Pecin, I. Pednekar, M.S. Peer, N. Pei, G. Peixoto, S.V. Peltonen, M. Pereira, A.C. Peres, M.A. Pérez-Farinós, N. Pérez, C.M. Peterkova, V. Peters, A. Petersmann, A. Petkeviciene, J. Petrauskiene, A. Pettenuzzo, E. Peykari, N. Pham, S.T. Pichardo, R.N. Pierannunzio, D. Pigeot, I. Pikhart, H. Pilav, A. Pilotto, L. Pistelli, F. Pitakaka, F. Piwonska, A. Pizarro, A.N. Plans-Rubió, P. Poh, B.K. Pohlabeln, H. Pop, R.M. Popovic, S.R. Porta, M. Posch, G. Poudyal, A. Poulimeneas, D. Pouraram, H. Pourfarzi, F. Pourshams, A. Poustchi, H. Pradeepa, R. Price, A.J. Price, J.F. Providencia, R. Puder, J.J. Pudule, I. Puhakka, S.E. Puiu, M. Punab, M. Qasrawi, R.F. Qorbani, M. Bao, T.Q. Radic, I. Radisauskas, R. Rahimikazerooni, S. Rahman, M. Rahman, M. Raitakari, O. Raj, M. Rakhimova, E. Rakhmatulloev, S. Rakovac, I. Rao, S.R. Ramachandran, A. Ramke, J. Ramos, E. Ramos, R. Rampal, L. Rampal, S. Rarra, V. Rascon-Pacheco, R.A. Rasmussen, M. Rech, C.R. Redon, J. Reganit, P.F.M. Regecová, V. Revilla, L. Rezaianzadeh, A. Ribas-Barba, L. Ribeiro, R. Riboli, E. Richter, A. Rigo, F. Rinaldo, N. de Wit, T.F.R. Rito, A. Ritti-Dias, R.M. Rivera, J.A. Robitaille, C. Roccaldo, R. Rodrigues, D. Rodríguez-Artalejo, F. del Cristo Rodriguez-Perez, M. Rodríguez-Villamizar, L.A. Roggenbuck, U. Rojas-Martinez, R. Rojroongwasinkul, N. Romaguera, D. Romeo, E.L. Rosario, R.V. Rosengren, A. Rouse, I. Roy, J.G.R. Rubinstein, A. Rühli, F.J. Ruidavets, J.-B. Ruiz-Betancourt, B.S. Ruiz-Castell, M. Moreno, E.R. Rusakova, I.A. Jonsson, K.R. Russo, P. Rust, P. Rutkowski, M. Sabanayagam, C. Sacchini, E. Sachdev, H.S. Sadjadi, A. Safarpour, A.R. Safiri, S. Saki, N. Salanave, B. Martinez, E.S. Salmerón, D. Salomaa, V. Salonen, J.T. Salvetti, M. Samoutian, M. Sánchez-Abanto, J. Sans, S. Marina, L.S. Santos, D.A. Santos, I.S. Santos, L.C. Santos, M.P. Santos, O. Santos, R. Sanz, S.S. Saramies, J.L. Sardinha, L.B. Sarrafzadegan, N. Sathish, T. Saum, K.-U. Savva, S. Savy, M. Sawada, N. Sbaraini, M. Scazufca, M. Schaan, B.D. Rosario, A.S. Schargrodsky, H. Schienkiewitz, A. Schipf, S. Schmidt, C.O. Schmidt, I.M. Schnohr, P. Schöttker, B. Schramm, S. Schramm, S. Schröder, H. Schultsz, C. Schutte, A.E. Sein, A.A. Selamat, R. Sember, V. Sen, A. Senbanjo, I.O. Sepanlou, S.G. Sequera, V. Serra-Majem, L. Servais, J. Ševcíková, L. Shalnova, S.A. Shamah-Levy, T. Shamshirgaran, M. Shanthirani, C.S. Sharafkhah, M. Sharma, S.K. Shaw, J.E. Shayanrad, A. Shayesteh, A.A. Shengelia, L. Shi, Z. Shibuya, K. Shimizu-Furusawa, H. Shin, D.W. Shirani, M. Shiri, R. Shrestha, N. Si-Ramlee, K. Siani, A. Siantar, R. Sibai, A.M. Silva, A.M. Silva, D.A.S. Simon, M. Simons, J. Simons, L.A. Sjöberg, A. Sjöström, M. Skodje, G. Slowikowska-Hilczer, J. Slusarczyk, P. Smeeth, L. So, H.-K. Soares, F.C. Sobek, G. Sobngwi, E. Sodemann, M. Söderberg, S. Soekatri, M.Y.E. Soemantri, A. Sofat, R. Solfrizzi, V. Somi, M.H. Sonestedt, E. Song, Y. Sørensen, T.I.A. Sørgjerd, E.P. Jérome, C.S. Soto-Rojas, V.E. Soumaré, A. Sovic, S. Sparboe-Nilsen, B. Sparrenberger, K. Spinelli, A. Spiroski, I. Staessen, J.A. Stamm, H. Stathopoulou, M.G. Staub, K. Stavreski, B. Steene-Johannessen, J. Stehle, P. Stein, A.D. Stergiou, G.S. Stessman, J. Stevanovic, R. Stieber, J. Stöckl, D. Stocks, T. Stokwiszewski, J. Stoyanova, E. Stratton, G. Stronks, K. Strufaldi, M.W. Sturua, L. Suárez-Medina, S. Suka, M. Sun, C.-A. Sundström, J. Sung, Y.-T. Sunyer, J. Suriyawongpaisal, P. Swinburn, B.A. Sy, R.G. Syddall, H.E. Sylva, R.C. Szklo, M. Szponar, L. Tai, E.S. Tammesoo, M.-L. Tamosiunas, A. Tan, E.J. Tang, X. Tanrygulyyeva, M. Tanser, F. Tao, Y. Tarawneh, M.R. Tarp, J. Tarqui-Mamani, C.B. Braunerová, R.T. Taylor, A. Taylor, J. Tchibindat, F. Tebar, W.R. Tell, G.S. Tello, T. Tham, Y.C. Thankappan, K.R. Theobald, H. Theodoridis, X. Thijs, L. Thomas, N. Thuesen, B.H. Tichá, L. Timmermans, E.J. Tjonneland, A. Tolonen, H.K. Tolstrup, J.S. Topbas, M. Topór-Madry, R. Torheim, L.E. Tormo, M.J. Tornaritis, M.J. Torrent, M. Torres-Collado, L. Toselli, S. Touloumi, G. Traissac, P. Tran, T.T.-H. Trichopoulos, D. Trichopoulou, A. Trinh, D.T.H. Trivedi, A. Tshepo, L. Tsigga, M. Tsugane, S. Tuliakova, A.M. Tulloch-Reid, M.K. Tullu, F. Tuomainen, T.-P. Tuomilehto, J. Turley, M.L. Twig, G. Tynelius, P. Tzotzas, T. Tzourio, C. Ueda, P. Ugel, E. Ukoli, F.A.M. Ulmer, H. Unal, B. Usupova, Z. Uusitalo, H.M.T. Uysal, N. Vaitkeviciute, J. Valdivia, G. Vale, S. Valvi, D. van Dam, R.M. Van der Heyden, J. van der Schouw, Y.T. Van Herck, K. Van Minh, H. Van Schoor, N.M. van Valkengoed, I.G.M. Vanderschueren, D. Vanuzzo, D. Varbo, A. Varela-Moreiras, G. Varona-Pérez, P. Vasan, S.K. Vega, T. Veidebaum, T. Velasquez-Melendez, G. Velika, B. Veronesi, G. Verschuren, W.M.M. Victora, C.G. Viegi, G. Viet, L. Villalpando, S. Vineis, P. Vioque, J. Virtanen, J.K. Visser, M. Visvikis-Siest, S. Viswanathan, B. Vladulescu, M. Vlasoff, T. Vocanec, D. Vollenweider, P. Völzke, H. Voutilainen, A. Voutilainen, S. Vrijheid, M. Vrijkotte, T.G.M. Wade, A.N. Wagner, A. Waldhör, T. Walton, J. Wambiya, E.O.A. Bebakar, A.M.W. Mohamud, W.N.W. de Souza Wanderley Júnior, R. Wang, M.-D. Wang, N. Wang, Q. Wang, X. Wang, Y.X. Wang, Y.-W. Wannamethee, S.G. Wareham, N. Weber, A. Wedderkopp, N. Weerasekera, D. Weghuber, D. Wei, W. Weres, A. Werner, B. Whincup, P.H. Widhalm, K. Widyahening, I.S. Wiecek, A. Wilks, R.J. Willeit, J. Willeit, P. Williams, J. Wilsgaard, T. Wojtyniak, B. Wong-McClure, R.A. Wong, A. Wong, J.E. Wong, T.Y. Woo, J. Woodward, M. Wu, F.C. Wu, J. Wu, L.J. Wu, S. Xu, H. Xu, L. Yaacob, N.A. Yamborisut, U. Yan, W. Yang, L. Yang, X. Yang, Y. Yardim, N. Yaseri, M. Yasuharu, T. Ye, X. Yiallouros, P.K. Yoosefi, M. Yoshihara, A. You, Q.S. You, S.-L. Younger-Coleman, N.O. Yusof, S.M. Yusoff, A.F. Zaccagni, L. Zafiropulos, V. Zainuddin, A.A. Zakavi, S.R. Zamani, F. Zambon, S. Zampelas, A. Zamrazilová, H. Zapata, M.E. Zargar, A.H. Zaw, K.K. Zdrojewski, T. Zejglicova, K. Vrkic, T.Z. Zeng, Y. Zhang, L. Zhang, Z.-Y. Zhao, D. Zhao, M.-H. Zhao, W. Zhen, S. Zheng, W. Zheng, Y. Zholdin, B. Zhou, M. Zhu, D. Zins, M. Zitt, E. Zocalo, Y. Cisneros, J.Z. Zuziak, M. Ezzati, M. Filippi, S. NCD Risk Factor Collaboration (NCD-RisC)

Subjects
nutritional and metabolic diseases, sense organs, skin and connective tissue diseases
Abstract

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions. © Copyright.

Published
2021

41. The role of the G protein-coupled receptor GPR30 in the effects of estrogen in ovariectomized mice

Author

Windahl, S.H., Andersson, N., Chagin, A.S., Martensson, U.E.A., Carlsten, H., Olde, B., Swanson, C., Moverare-Skrtic, S., Savendahl, L., Lagerquist, M.K., Leeb-Lundberg, L.M.F., and Ohlsson, C.

Subjects
Estrogen -- Receptors, Estrogen -- Properties, Bones -- Growth, Bones -- Research, Biological sciences
Abstract

In vitro studies suggest that the membrane G protein-coupled receptor GPR30 is a functional estrogen receptor (ER). The aim of the present study was to determine the possible in vivo role of GPR30 as a functional ER primarily for the regulation of skeletal parameters, including bone mass and longitudinal bone growth, but also for some other well-known estrogen-regulated parameters, including uterine weight, thymus weight, and fat mass. Three-month-old ovariectomized (OVX) GPR30-deficient mice ([GPR30.sup.-/-]) and wild-type (WT) mice were treated with either vehicle or increasing doses of estradiol ([E.sub.2]; 0, 30, 70, 160, or 830 ng x [mouse.sup.-1] x [day.sup.-1]). Body composition [bone mineral density (BMD), fat mass, and lean mass] was analyzed by dual-energy-X ray absorptiometry, while the cortical and trabecular bone compartments were analyzed by peripheral quantitative computerized tomography. Quantitative histological analyses were performed in the distal femur growth plate. Bone marrow cellularity and distribution were analyzed using a fluorescence-activated cell sorter. The estrogenic responses on most of the investigated parameters, including increase in bone mass (total body BMD, spine BMD, trabecular BMD, and cortical bone thickness), increase in uterine weight, thymic atrophy, fat mass reduction, and increase in bone marrow cellularity, were similar for all of the investigated [E.sub.2] doses in WT and [GPR30.sup.-/-] mice. On the other hand, [E.sub.2] treatment reduced longitudinal bone growth, reflected by decreased femur length and distal femur growth plate height, in the WT mice but not in the [GPR30.sup.-/-] mice compared with vehicle-treated mice. These in vivo findings demonstrate that GPR30 is not required for normal estrogenic responses on several major well-known estrogen-regulated parameters. In contrast, GPR30 is required for a normal estrogenic response in the growth plate. estrogen receptor; growth; bone

Published
2009

45. Erbb4 regulates the oocyte microenvironment during folliculogenesis

Author

Veikkolainen, V. (Ville), Ali, N. (Nsrein), Doroszko, M. (Milena), Kiviniemi, A. (Antti), Miinalainen, I. (Ilkka), Ohlsson, C. (Claes), Poutanen, M. (Matti), Rahman, N. (Nafis), Elenius, K. (Klaus), Vainio, S. J. (Seppo J.), and Naillat, F. (Florence)

Subjects
endocrine system
Abstract

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders leading to infertility in women affecting reproductive, endocrine and metabolic systems. Recent genomewide association studies on PCOS cohorts revealed a single nucleotide polymorphism (SNP) in the ERBB4 receptor tyrosine kinase 4 gene, but its role in ovary development or during folliculogenesis remains poorly understood. Since no genetic animal models mimicking all PCOS reproductive features are available, we conditionally deleted Erbb4 in murine granulosa cells (GCs) under the control of Amh promoter. While we have demonstrated that Erbb4 deletion displayed aberrant ovarian function by affecting the reproductive function (asynchronous oestrous cycle leading to few ovulations and subfertility) and metabolic function (obesity), their ovaries also present severe structural and functional abnormalities (impaired oocyte development). Hormone analysis revealed an up-regulation of serum luteinizing hormone, hyperandrogenism, increased production of ovarian and circulating anti-Müllerian hormone. Our data implicate that Erbb4 deletion in GCs leads to defective intercellular junctions between the GCs and oocytes, causing changes in the expression of genes regulating the local microenvironment of the follicles. In vitro culture assays reducing the level of Erbb4 via shRNAs confirm that Erbb4 is essential for regulating Amh level. In conclusion, our results indicate a functional role for Erbb4 in the ovary, especially during folliculogenesis and its reduced expression plays an important role in reproductive pathophysiology, such as PCOS development.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results