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2. Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases

Author

Carland, Corinne, Png, Grace, Malarstig, Anders, Kho, Pik Fang, Gustafsson, Stefan, Michaelsson, Karl, Lind, Lars, Tsafantakis, Emmanouil, Karaleftheri, Maria, Dedoussis, George, Ramisch, Anna, Macdonald-Dunlop, Erin, Klaric, Lucija, Joshi, Peter K., Chen, Yan, Björck, Hanna M., Eriksson, Per, Carrasco-Zanini, Julia, Wheeler, Eleanor, Suhre, Karsten, Gilly, Arthur, Zeggini, Eleftheria, Viñuela, Ana, Dermitzakis, Emmanouil T., Wilson, James F., Langenberg, Claudia, Thareja, Gaurav, Halama, Anna, Schmidt, Frank, Zanetti, Daniela, and Assimes, Themistocles

Published
2023
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5. Adaptation of the Charlson Comorbidity Index for Register-Based Research in Sweden [Corrigendum]

Author

Ludvigsson, Jonas F, primary, Appelros, Peter, additional, Askling, Johan, additional, Byberg, Liisa, additional, Carrero, Juan-Jesus, additional, Ekström, Anna Mia, additional, Ekström, Magnus, additional, Smedby, Karin Ekström, additional, Hagström, Hannes, additional, James, Stefan, additional, Järvholm, Bengt, additional, Michaelsson, Karl, additional, Pedersen, Nancy L, additional, Sundelin, Helene, additional, Sundquist, Kristina, additional, and Sundström, Johan, additional

Published
2023
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7. Body Size and Hip Fracture Risk

Author

Farahmand, Bahman Y., Michaëlsson, Karl, Baron, John A., Persson, Per-Gunnar, and Ljunghall, Sverker

Published
2000

17. LifeGene—a large prospective population-based study of global relevance

Author

Almqvist, Catarina, Adami, Hans-Olov, Franks, Paul W., Groop, Leif, Ingelsson, Erik, Kere, Juha, Lissner, Lauren, Litton, Jan-Eric, Maeurer, Markus, Michaëlsson, Karl, Palmgren, Juni, Pershagen, Göran, Ploner, Alexander, Sullivan, Patrick F., Tybring, Gunnel, and Pedersen, Nancy L.

Published
2011

22. Adaptation of the Charlson Comorbidity Index for Register-Based Research in Sweden

Author

Ludvigsson, Jonas F, primary, Appelros, Peter, additional, Askling, Johan, additional, Byberg, Liisa, additional, Carrero, Juan-Jesus, additional, Ekström, Anna Mia, additional, Ekström, Magnus, additional, Smedby, Karin Ekström, additional, Hagström, Hannes, additional, James, Stefan, additional, Järvholm, Bengt, additional, Michaelsson, Karl, additional, Pedersen, Nancy L, additional, Sundelin, Helene, additional, Sundquist, Kristina, additional, and Sundström, Johan, additional

Published
2021
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24. Leisure physical activity and the risk of fracture in men

Author

Michaelsson, Karl, Olofsson, Helena, Jensevik, Karin, Larsson, Sune, Mallmin, Hans, Berglund, Lars, Vessby, Bengt, and Melhus, Hakan

Subjects
Exercise -- Risk factors, Fractures -- Causes of, Fractures -- Demographic aspects, Fractures -- Prevention, Men -- Injuries, Men -- Surveys, Exercise for men -- Risk factors
Abstract

ABSTRACT Background Data from previous studies are inconsistent, and it is therefore uncertain whether, to what extent, and at what level leisure physical activity influences the risk of osteoporotic fractures [...]

Published
2007

25. Plasma vitamin D and mortality in older men: a community-based prospective cohort study

Author

Michaelsson, Karl, Baron, John A., Snellman, Greta, Gedeborg, Rolf, Byberg, Liisa, Sundstrom, Johan, Berglund, Lars, Arnlov, Johan, Hellman, Per, Blomhoff, Rune, Wolk, Alicja, Garmo, Hans, Holmberg, Lars, and Melhus, Hakan

Subjects
Aged -- Health aspects, Aged -- Physiological aspects, Mortality -- United States, Mortality -- Research, Alfacalcidol -- Physiological aspects, Alfacalcidol -- Research, Calcifediol -- Physiological aspects, Calcifediol -- Research, Vitamin D -- Physiological aspects, Vitamin D -- Research, Food/cooking/nutrition, Health
Abstract

Background: Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death. Objective: We aimed to examine how vitamin D status relates to overall and cause-specific mortality. Design: The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs). Results: During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk. Conclusions: Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality. Am J Clin Nutr 2010;92:841-8. doi: 10.3945/ajcn.2010.29749.

Published
2010

26. MOESM1 of Sarcopenia prevalence and associations with mortality and hospitalisation by various sarcopenia definitions in 85–89 year old community-dwelling men: a report from the ULSAM study

Author

Sobestiansky, Sigvard, Michaelsson, Karl, and Cederholm, Tommy

Abstract

Additional file 1: Table S1. Rate ratios (95% CI) for number of hospitalisations during three-year follow-up according to muscle mass and body composition, muscle strength and physical performance. Table S2. Rate ratios (95% CI) for days of hospitalisation during three-year follow-up according to muscle mass and body composition, muscle strength and physical performance.

Published
2019
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27. Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis (vol 101, pg 227, 2017)

Author

Manousaki, Despoina, Dudding, Tom, Haworth, Simon, Hsu, Yi-Hsiang, Liu, Ching-Ti, Medina-Gomez, Carolina, Voortman, Trudy, van der Velde, Nathalie, Melhus, Hakan, Robinson-Cohen, Cassianne, Cousminer, Diana L., Nethander, Maria, Vandenput, Liesbeth, Noordam, Raymond, Forgetta, Vincenzo, Greenwood, Celia M. T., Biggs, Mary L., Psaty, Bruce M., Rotter, Jerome I., Zemel, Babette S., Mitchell, Jonathan A., Taylor, Bruce, Lorentzon, Mattias, Karlsson, Magnus, Jaddoe, Vincent V. W., Tiemeier, Henning, Campos-Obando, Natalia, Franco, Oscar H., Utterlinden, Andre G., Broer, Linda, van Schoor, Natasja M., Ham, Annelies C., Ikram, M. Arfan, Karasik, David, de Mutsert, Renee, Rosendaal, Frits R., den Heijer, Martin, Wang, Thomas J., Lind, Lars, Orwoll, Eric S., Mook-Kanamori, Dennis O., Michaelsson, Karl, Kestenbaum, Bryan, Ohlsson, Claes, Mellstrom, Dan, de Groot, Lisette C. P. G. M., Grant, Struan F. A., Kiel, Douglas P., Zillikens, M. Carola, Rivadeneira, Fernando, Sawcer, Stephen, Timpson, Nicholas J., Richards, J. Brent, General practice, APH - Aging & Later Life, Epidemiology and Data Science, Internal medicine, AGEM - Endocrinology, metabolism and nutrition, Amsterdam Movement Sciences - Rehabilitation & Development, Amsterdam Movement Sciences - Restoration and Development, and APH - Personalized Medicine

Published
2018

28. Conflicts at the heart of the FRAX tool

Author

Jarvinen, Teppo L.N., Jokihaara, Jarkko, Guy, Pierre, Alonso-Coello, Pablo, Collins, Gary S., Michaelsson, Karl, and Sievanen, Harri

Subjects
Osteoporosis -- Complications and side effects, Fractures -- Risk factors -- Diagnosis, Bone densitometry -- Evaluation, Health risk assessment, Health
Abstract

Although the presence of osteoporosis, on average, predicts future fractures at the population level, accumulating evidence indicates that both the identification of fracture-prone individuals and the effectiveness of bone-targeted medications [...]

Published
2014
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29. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass (vol 8, 80, 2017)

Author

Zillikens, M Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M, Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L, Kutalik, Zoltan, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Zhao, Jing Hua, Zhang, Weihua, Aghdassi, Ali, Akesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Ines, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Obanda, Natalia Campos, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Choi, Hyung Jin, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie AM, Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W, Erdos, Mike, Eriksson, Johan G, Eriksson, Joel, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L, Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L, Hayward, Caroline, Hofman, Albert, Hoffman, Eric P, Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J, Hubbard, Alan, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpelanen, Tuomas O, Klopp, Norman, Kloth, Jacqueline SL, Koistinen, Heikki A, Kraus, William E, Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Launer, Lenore J, Lee, Jong-Young, Lerch, Markus M, Lewis, Joshua R, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Liu, Tian, Liu, Youfang, Ljunggren, Osten, Lorentzon, Mattias, Luben, Robert N, Maixner, William, McGuigan, Fiona E, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Hakan, Mellstrom, Dan, Melov, Simon, Michaelsson, Karl, Mitchell, Braxton D, Morris, Andrew P, Mosekilde, Leif, Newman, Anne, Nielson, Carrie M, O'Connell, Jeffrey R, Oostra, Ben A, Orwoll, Eric S, Palotie, Aarno, Parker, Stephen CJ, Peacock, Munro, Perola, Markus, Peters, Annette, Polasek, Ozren, Prince, Richard L, Raikkonen, Katri, Ralston, Stuart H, Ripatti, Samuli, Robbins, John A, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Satterfield, Suzanne, Schadt, Eric E, Schipf, Sabine, Scott, Laura, Sehmi, Joban, Shen, Jian, Shin, Chan Soo, Sigurdsson, Gunnar, Smith, Shad, Soranzo, Nicole, Stancakova, Alena, Steinhagen-Thiessen, Elisabeth, Streeten, Elizabeth A, Styrkarsdottir, Unnur, Swart, Karin MA, Tan, Sian-Tsung, Tarnopolsky, Mark A, Thompson, Patricia, Thomson, Cynthia A, Thorsteinsdottir, Unnur, Tikkanen, Emmi, Tranah, Gregory J, Tuomilehto, Jaakko, van Schoor, Natasja M, Verma, Arjun, Vollenweider, Peter, Volzke, Henry, Wactawski-Wende, Jean, Walker, Mark, Weedon, Michael N, Welch, Ryan, Wichmann, H-Erich, Widen, Elisabeth, Williams, Frances MK, Wilson, James F, Wright, Nicole C, Xie, Weijia, Yu, Lei, Zhou, Yanhua, Chambers, John C, Doring, Angela, van Duijn, Cornelia M, Econs, Michael J, Gudnason, Vilmundur, Kooner, Jaspal S, Psaty, Bruce M, Spector, Timothy D, Stefansson, Kari, Rivadeneira, Fernando, Uitterlinden, Andre G, Wareham, Nicholas J, Ossowski, Vicky, Waterworth, Dawn, Loos, Ruth JF, Karasik, David, Harris, Tamara B, Ohlsson, Claes, and Kiel, Douglas P

Published
2017

33. Genetic effects on physical activity: Results from the Swedish Twin Registry

Author

Carlsson, Sofia, Andersson, Tomas, Lichtenstein, Paul, Michaelsson, Karl, and Ahlbom, Anders

Subjects
Exercise -- Genetic aspects, Exercise -- Health aspects, Heredity -- Analysis, Health, Sports and fitness
Abstract

A study was conducted to investigate the genetic effects on leisure-time physical activity using data from the Swedish Twin Registry. The results from study established heredity as an important component behind individual differences in physical activity in adult men and women, which might be one reason behind difficulties in convincing people to adopt an active lifestyle.

Published
2006

36. Serum Calcium and Risk of Gastrointestinal Cancer

Author

Wulaningsih, Wahyu, primary, Michaelsson, Karl, additional, Garmo, Hans, additional, Hammar, Niklas, additional, Jungner, Ingmar, additional, Walldius, Göran, additional, Lambe, Mats, additional, Holmberg, Lars, additional, and Van Hemelrijck, Mieke, additional

Published
2013
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41. Transforming growth factor β1genotype and change in left ventricular mass during antihypertensive treatment-results from the swedish irbesartan left ventricular hypertrophy investigation versus atenolol (Silvhia)

Author

Hallberg, Pär, primary, Lind, Lars, additional, Billberger, Katarina, additional, Michaelsson, Karl, additional, Karlsson, Julia, additional, Kurland, Lisa, additional, Kahan, Thomas, additional, Malmqvist, Karin, additional, Öhman, K. Peter, additional, Nyström, Fredrik, additional, Liljedahl, Ulrika, additional, Syvänen, Ann-Christine, additional, and Melhus, Håkan, additional

Published
2004
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42. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author

Lu, Yingchang, Day, Felix R., Gustafsson, Stefan, Buchkovich, Martin L., Na, Jianbo, Bataille, Veronique, Cousminer, Diana L., Dastani, Zari, Drong, Alexander W., Esko, Tõnu, Evans, David M., Falchi, Mario, Feitosa, Mary F., Ferreira, Teresa, Hedman, Åsa K., Haring, Robin, Hysi, Pirro G., Iles, Mark M., Justice, Anne E., Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R. B., Pers, Tune H., Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M., Scott, William R., Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A. E., Walker, Ryan W., Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J. L., Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S., Cederholm, Tommy, Choh, Audrey C., Choi, Hyung Jin, Curran, Joanne E., de Groot, Lisette C. P. G. M., De Jager, Philip L., Dhonukshe-Rutten, Rosalie A. M., Enneman, Anke W., Eury, Elodie, Evans, Daniel S., Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E., Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S., Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W., Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Leach, Irene Mateo, Lee, Christine G., Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A., Nielson, Carrie M., Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A., Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M. A., Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M., Verweij, Niek, Wright, Alan F., Yu, Lei, Zmuda, Joseph M., Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U., Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D., Ried, Janina S., Scott, Robert A., Stancáková, Alena, Wagner, Peter J., Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P., Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R., Oostra, Ben A., Shuldiner, Alan R., Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M., Vollenweider, Peter, White, Charles C., Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S., Forouhi, Nita G., Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A., Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O., Wareham, Nicholas J., Bennett, David A., Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H., Cummings, Steven R., Czerwinski, Stefan A., Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G., Ferrucci, Luigi, Franco, Oscar H., Froguel, Philippe, Gansevoort, Ron T., Hansen, Torben, Harris, Tamara B., Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M., Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B., Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S., Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I. A., Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J., Tremblay, Angelo, Uitterlinden, André G., van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S., Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F., Yengo, Loïc, Bishop, D. Timothy, Borecki, Ingrid B., Chambers, John C., Cupples, L. Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S., Franke, Lude, Han, Jiali, Hunter, David J., Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C., Kooner, Jaspal S., McCarthy, Mark I., Murabito, Joanne M., Morris, Andrew P., Bishop, Julia A. N., North, Kari E., Ohlsson, Claes, Ong, Ken K., Prokopenko, Inga, Richards, J. Brent, Schadt, Eric E., Spector, Tim D., Widén, Elisabeth, Willer, Cristen J., Yang, Jian, Ingelsson, Erik, Mohlke, Karen L., Hirschhorn, Joel N., Pospisilik, John Andrew, Zillikens, M. Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, and Loos, Ruth J. F.

Abstract

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

Published
2016
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43. Transforming growth factor β1 genotype and change in left ventricular mass during antihypertensive treatment-results from the swedish irbesartan left ventricular hypertrophy investigation versus atenolol (Silvhia).

Author

Hallberg, Pär, Lind, Lars, Billberger, Katarina, Michaelsson, Karl, Karlsson, Julia, Kurland, Lisa, Kahan, Thomas, Malmqvist, Karin, Öhman, K. Peter, Nyström, Fredrik, Liljedahl, Ulrika, Syvänen, Ann-Christine, and Melhus, Håkan

Published
2004
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44. Causal Relationship Between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts

Author

Vimaleswaran, Karani S., Berry, Diane J., Lu, Chen, Tikkanen, Emmi, Pilz, Stefan, Hiraki, Linda T, Cooper, Jason D., Dastani, Zari, Li, Rui, Houston, Denise K., Wood, Andrew R., Michaëlsson, Karl, Vandenput, Liesbeth, Zgaga, Lina, Yerges-Armstrong, Laura M., McCarthy, Mark I., Dupuis, Josée, Kaakinen, Marika, Kleber, Marcus E., Jameson, Karen, Arden, Nigel, Raitakari, Olli, Viikari, Jorma, Lohman, Kurt K., Ferrucci, Luigi, Melhus, Håkan, Ingelsson, Erik, Byberg, Liisa, Lind, Lars, Lorentzon, Mattias, Salomaa, Veikko, Campbell, Harry, Dunlop, Malcolm, Mitchell, Braxton D., Herzig, Karl-Heinz, Pouta, Anneli, Hartikainen, Anna-Liisa, Streeten, Elizabeth A., Theodoratou, Evropi, Jula, Antti, Wareham, Nicholas J., Ohlsson, Claes, Frayling, Timothy M., Kritchevsky, Stephen B., Spector, Timothy D., Richards, J. Brent, Lehtimäki, Terho, Ouwehand, Willem H., Kraft, Peter, Cooper, Cyrus, März, Winfried, Power, Chris, Loos, Ruth J. F., Wang, Thomas Jue-Fuu, Järvelin, Marjo-Riitta, Whittaker, John C., Hingorani, Aroon D., Hyppönen, Elina, and Genetic Investigation of Anthropometric Traits (GIANT) consortium

Subjects
biology, genetics, population genetics, genetic polymorphism, population biology, epidemiology, genetic epidemiology
Abstract

Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each \(1 kg/m^{2}\) higher BMI was associated with 1.15% lower 25(OH)D \((p = 6.52×10^{−27})\). The BMI allele score was associated both with BMI \((p = 6.30×10^{−62})\) and 25(OH)D (−0.06% [95% CI −0.10 to −0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D \((p≤8.07×10^{−57}\) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: −4.2 [95% CI −7.1 to −1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency. Please see later in the article for the Editors' Summary.

Published
2013
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45. O-0019SERUM CALCIUM AND RISK OF GASTROINTESTINAL CANCER.

Author

Wulaningsih, Wahyu, Michaelsson, Karl, Garmo, Hans, Hammar, Niklas, Jungner, Ingmar, Walldius, Göran, Lambe, Mats, Holmberg, Lars, and Van Hemelrijck, Mieke

Subjects
*SERUM, *CALCIUM in the body, *GASTROINTESTINAL cancer, *MEDICAL informatics, *CANCER diagnosis, *CANCER-related mortality, *ANIMAL models in research
Published
2013
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46. Effect of Prefracture versus Postfracture Dietary Assessment on Hip Fracture Risk Estimates

Author

MICHAELSSON, KARL, HOLMBERG, LARS, LJUNGHALL, SVERKER, MALLMIN, HANS, PERSSON, PER-GUNNAR, WOLK, ALICJA, and SWEA), THE STUDY GROUP OF THE MULTIPLE RISK SURVEY ON SWEDISH WOMEN FOR EATING ASSESSMENT (MRS

Abstract

Background Dietary factors are presumed to have Influence on bone mass and hence fracture susceptibility. Most information in this respect is based on retrospective assessment of previous dietary habits. In a population-based case-control study nested within a cohort, we collected dietary information both before and after a first hip fracture. Thus it was possible to study reported changes in dietary habits, intentional as well as unintentional, among hip fracture patients after a first hip fracture and to compare postfracture with prefracture dietary information. Methods More than 65 000 women born 1914–1948 in two counties in central Sweden completed a food frequency questionnaire regarding their usual current dietary habits, before attending a mammographic screening between the years 1987 and 1990. Subsequently 123 of them sustained a first hip fracture and were defined as cases in the present study. For every case, one control, individually matched by age and county of residence, was selected from the cohort. A second identical food frequency questionnaire was mailed to both cases and controls on average 2 years after the hip fracture event. In total 98 case/control pairs could be included in the analysis. The association between diet and hip fracture was evaluated and the results from the two dietary assessments were contrasted. Women who themselves claimed that they had not changed their diet in recent years were analysed separately. Results The hip fracture cases, compared with the controls, had reduced their reported dietary intake of dairy products after the fracture. Apparently this was not intentional since this effect was more pronounced among those cases who claimed that their diet was unchanged. The changes were most apparent among the younger cases with a more recent hip fracture and with a body mass index above the median. Half of the cases, more than twice the frequency in controls, who were initialiy classified as having high intake of dairy products were classified as having low intake (<800 mg calcium/day) after the hip fracture. This also lowered, in fact reversed, the relative risk estimates of hip fracture both for intake of dairy products and calcium. Crude odds ratios of highest quartile of intake versus lowest, changed from 3.0 to 0.6 for dairy products and from 2.6 to 0.9 for calcium. No other foods or nutrients displayed such notable differences between the two surveys. Conclusions We conclude that the use of current and retrospective dietary information after a hip fracture can lead to a differential misclassification in dietary studies and to biased estimates of hip fracture risk as compared with prospectively collected dietary information

Published
1996
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47. Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals

Author

Tom Palmer, Lars Lind, George Davey Smith, Ting Qi, Michael W. Nagle, Paul W. Franks, Bram P. Prins, Julie Lee, Jingyuan Fu, Niclas Eriksson, Peter K. Joshi, Chris Haley, Ljubica Perisic Matic, Jeremy D. Gale, Mika Ala-Korpela, Michael V. Holmes, Urmo Võsa, Adam S. Butterworth, Eric B. Fauman, Anette Kalnapenkis, Reedik Mägi, Åsa Johansson, James F. Wilson, Mikael Landén, Gunnar Engström, Johan Ärnlöv, Anders Hamsten, Ozren Polasek, Andres Ingason, Andrew J. Schork, Agneta Siegbahn, Lasse Folkersen, Qin Wang, Andrew P. Morris, Johan Sundström, Daria V. Zhernakova, Olle Melander, Erik Ingelsson, Federico De Masi, Lude Franke, James E. Peters, Alexandra Zhernakova, Seung Hoan Choi, Rasmus Wernersson, Thibaud Boutin, Karl Michaëlsson, Stefan Gustafsson, Bianca E. Suur, Karen Page, Yang Wu, Caroline Hayward, Marketa Sjögren, Cecilia M. Lindgren, Stefan Enroth, Tõnu Esko, Amira Quazi, John Danesh, Anders Mälarstig, Daniel Hvidberg Hansen, Åsa K Hedman, Jan Nilsson, Ulf Gyllensten, Vilmantas Giedraitis, J. Gustav Smith, Martin Magnusson, Marju Orho-Melander, Steven A. Lubitz, Erin Macdonald-Dunlop, Thomas Werge, Praveen Surendran, Yan Chen, Céline Fernandez, Weidong Zhang, Lars Wallentin, Andrew D. Bretherick, Jian Yang, Peter M. Nilsson, Jesper R. Gådin, Annique Claringbould, Sölve Elmståhl, Sarah E Bergen, Harm-Jan Westra, Erik Pålsson, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), United Kingdom Research and Innovation, Folkersen, Lasse [0000-0003-0708-9530], Hansen, Daniel Hvidberg [0000-0003-3285-605X], Wu, Yang [0000-0002-0128-7280], Eriksson, Niclas [0000-0002-2152-4343], Bretherick, Andrew D [0000-0001-9258-3140], Enroth, Stefan [0000-0002-5056-9137], Lee, Julie [0000-0001-6090-6718], Ala-Korpela, Mika [0000-0001-5905-1206], Claringbould, Annique [0000-0002-9201-6557], Davey Smith, George [0000-0002-1407-8314], Fauman, Eric [0000-0002-9739-0249], Fernandez, Celine [0000-0003-1290-4982], Franke, Lude [0000-0002-5159-8802], Franks, Paul W [0000-0002-0520-7604], Giedraitis, Vilmantas [0000-0003-3423-2021], Haley, Chris [0000-0002-9811-0210], Johansson, Åsa [0000-0002-2915-4498], Lubitz, Steven [0000-0002-9599-4866], Palmer, Tom [0000-0003-4655-4511], Macdonald-Dunlop, Erin [0000-0001-6569-6086], Magnusson, Martin [0000-0003-1710-5936], Michaelsson, Karl [0000-0003-2815-1217], Nagle, Michael W [0000-0002-4677-7582], Nilsson, Peter M [0000-0002-5652-8459], Nilsson, Jan [0000-0002-9752-7479], Prins, Bram [0000-0001-5774-034X], Sundström, Johan [0000-0003-2247-8454], Werge, Thomas [0000-0003-1829-0766], Westra, Harm-Jan [0000-0001-7038-567X], Fu, Jingyuan [0000-0001-5578-1236], Esko, Tõnu [0000-0003-1982-6569], Hayward, Caroline [0000-0002-9405-9550], Landen, Mikael [0000-0002-4496-6451], Butterworth, Adam S [0000-0002-6915-9015], Holmes, Michael V [0000-0001-6617-0879], Ingelsson, Erik [0000-0003-2256-6972], Mälarstig, Anders [0000-0003-2608-1358], Apollo - University of Cambridge Repository, and 30387078 - Magnusson, P. Martin

Subjects
Proteomics, Proteome, Endocrinology, Diabetes and Metabolism, Asthma, ATP Binding Cassette Transporter 1, Cardiovascular System, Chromosome Mapping, Drug Delivery Systems, Gene Knockdown Techniques, Genome-Wide Association Study, Genomics, Humans, Inflammatory Bowel Diseases, Interleukin-1 Receptor-Like 1 Protein, Intracellular Signaling Peptides and Proteins, Linkage Disequilibrium, Mendelian Randomization Analysis, Protein-Serine-Threonine Kinases, Quantitative Trait Loci, Receptors, CCR2, Receptors, CCR5, Genome-wide association study, 030204 cardiovascular system & hematology, Chemokine receptor, 0302 clinical medicine, RECEPTOR ANTAGONIST, GWAS, Cardiac and Cardiovascular Systems, 0303 health sciences, Molecular medicine, 3. Good health, Medical genetics, Medical Genetics, Life Sciences & Biomedicine, medicine.medical_specialty, Computational biology, Biology, Protein Serine-Threonine Kinases, Article, 03 medical and health sciences, Endocrinology & Metabolism, Physiology (medical), Mendelian randomization, Internal Medicine, medicine, 030304 developmental biology, Science & Technology, Cell Biology, GENE, ANTIBODY
Abstract

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.

Published
2020
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48. Transforming growth factor beta1 genotype and change in left ventricular mass during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).

Author

Hallberg P, Lind L, Billberger K, Michaelsson K, Karlsson J, Kurland L, Kahan T, Malmqvist K, Ohman KP, Nyström F, Liljedahl U, Syvänen AC, and Melhus H

Subjects
Atenolol therapeutic use, Double-Blind Method, Female, Genotype, Humans, Hypertension complications, Hypertrophy, Left Ventricular complications, Hypertrophy, Left Ventricular physiopathology, Irbesartan, Linear Models, Male, Polymorphism, Genetic, Sweden, Treatment Outcome, Antihypertensive Agents therapeutic use, Biphenyl Compounds therapeutic use, Hypertension drug therapy, Hypertrophy, Left Ventricular drug therapy, Tetrazoles therapeutic use, Transforming Growth Factor beta genetics
Abstract

Background: Angiotensin II, via the angiotensin II type 1 (AT1) receptor, may mediate myocardial fibrosis and myocyte hypertrophy seen in hypertensive left ventricular (LV) hypertrophy through production of transforming growth factor beta1 (TGF-beta1); AT1-receptor antagonists reverse these changes. The TGF-beta1 G + 915C polymorphism is associated with interindividual variation in TGF-beta1 production. No study has yet determined the impact of this polymorphism on the response to antihypertensive treatment., Hypothesis: We aimed to determine whether the TGF-beta1 G + 915C polymorphism was related to change in LV mass during antihypertensive treatment with either an AT1-receptor antagonists or a beta1-adrenoceptor blocker. The polymorphism was hypothesized to have an impact mainly on the irbesartan group., Methods: We determined the association between the TGF-beta1 genotype and regression of LV mass in 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, randomized in a double-blind study to receive treatment for 48 weeks with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol., Results: Irbesartan-treated patients who were carriers of the C-allele, which is associated with low expression of TGF-beta1, responded with a markedly greater decrease in LV mass index (LVMI) than subjects with the G/G genotype (adjusted mean change in LVMI -44.7 g/m2 vs. -22.2 g/m2, p = 0.007), independent of blood pressure reduction. No association between genotype and change in LVMI was observed in the atenolol group., Conclusions: The TGF-beta1 G + 915C polymorphism is related to the change in LVMI in response to antihypertensive treatment with the AT1-receptor antagonist irbesartan.

Published
2004
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