Association of genetically predicted serum estradiol with risk of thromboembolism in men : A mendelian randomization study

Journal article

Nethander, Maria, Quester, Johan, Vandenput, Liesbeth and Ohlsson, Claes. (2021). Association of genetically predicted serum estradiol with risk of thromboembolism in men : A mendelian randomization study. The Journal of Clinical Endocrinology and Metabolism. 106(8), pp. 3078-3086. https://doi.org/10.1210/clinem/dgab164
AuthorsNethander, Maria, Quester, Johan, Vandenput, Liesbeth and Ohlsson, Claes
Abstract

Context
An association was recently reported between genetic markers related to high testosterone and increased risk of thromboembolism in men, but a possible causal role of estradiol for risk of thromboembolism in men remains unknown.

Objective
This work aimed to determine whether endogenous estradiol has a causal role in thromboembolism in men.

Methods
A 2-sample mendelian randomization study using gene-based genetic instruments assessed the association between endogenous estradiol genetically predicted by 22 variants in the aromatase CYP19A1 gene region and the risk of thromboembolism (5815 cases) in 170 593 unrelated men of White ancestry in the UK Biobank. The main outcome measure included thromboembolism based on self-reports, hospital episodes, and death.

Results
Endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of thromboembolism (odds ratio per SD increase in estradiol 0.74; 95% CI, 0.62-0.90). In contrast, genetic variants in the JMJD1C gene, used as a predictor of high endogenous testosterone, were associated with an increased risk of thromboembolism (odds ratio per SD increase in testosterone 1.39; 95% CI, 1.12-1.72). Subsequent explorative analyses evaluating potential repercussions of thromboembolism revealed that endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of ischemic stroke (0.68; 95% CI, 0.49-0.95) but not myocardial infarction (0.97; 95% CI, 0.84-1.13).

Conclusion
Genetically predicted estradiol was inversely associated with the risk of thromboembolism and ischemic stroke in men. The ratio between testosterone and estradiol, determined by CYP19A1 activity, may contribute to the overall impact of sex steroids on thromboembolism in men.

Keywordstestosterone; estradiol; thromboembolism; aromatase; mendelian; randomization
Year2021
JournalThe Journal of Clinical Endocrinology and Metabolism
Journal citation106 (8), pp. 3078-3086
PublisherOxford University Press
ISSN0021-972X
Digital Object Identifier (DOI)https://doi.org/10.1210/clinem/dgab164
PubMed ID33705547
Scopus EID2-s2.0-85111937303
PubMed Central IDPMC8277207
Open accessPublished as ‘gold’ (paid) open access
Research or scholarlyResearch
Page range3078-3086
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online11 Mar 2021
Publication process dates
Deposited09 Nov 2021
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Genome analyses of > 200,000 individuals identify 58 loci for chronic inflammation and highlight pathways that link inflammation and complex disorders
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Assessment of the genetic and clinical determinants of fracture risk: Genome wide association and mendelian randomisation study
Trajanoska, Katerina, Morris, John A., Oei, Ling, Zheng, Hou-Feng, Evans, David M., Kiel, Douglas P., Ohlsson, Claes, Richards, J. Brent, Rivadeneira, Fernando, on behalf of the GEFOS/GENOMOS consortium and the 23andMe research team*, Lorentzon, Mattias and Vandenput, Liesbeth. (2018). Assessment of the genetic and clinical determinants of fracture risk: Genome wide association and mendelian randomisation study. BMJ. 362, p. Article k3225. https://doi.org/10.1136/bmj.k3225
Serum DHEA and Its Sulfate Are Associated With Incident Fall Risk in Older Men: The MrOS Sweden study
Ohlsson, Claes, Nethander, Maria, Karlsson, Magnus K., Rosengren, Björn E., Ribom, Eva, Mellström, Dan and Vandenput, Liesbeth. (2018). Serum DHEA and Its Sulfate Are Associated With Incident Fall Risk in Older Men: The MrOS Sweden study. Journal of Bone and Mineral Research. 33(7), pp. 1227 - 1232. https://doi.org/10.1002/jbmr.3418
Genetic determinants of circulating estrogen levels and evidence of a causal effect of estradiol on bone density in men
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The limited clinical utility of testosterone, estradiol, and sex hormone binding globulin measurements in the prediction of fracture risk and bone loss in older men
Orwoll, Eric S., Lapidus, Jodi, Wang, Patty Y., Vandenput, Liesbeth, Hoffman, Andrew, Fink, Howard A., Laughlin, Gail A., Nethander, Maria, Ljunggren, Östen, Kindmark, Andreas, Lorentzon, Mattias, Karlsson, Magnus K., Mellström, Dan, Kwok, Anthony, Khosla, Sundeep, Kwok, Timothy and Ohlsson, Claes. (2017). The limited clinical utility of testosterone, estradiol, and sex hormone binding globulin measurements in the prediction of fracture risk and bone loss in older men. Journal of Bone and Mineral Research. 32(3), pp. 633-640. https://doi.org/10.1002/jbmr.3021
Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
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Umbilical cord blood androgen levels in girls and boys assessed by gas chromatography-tandem mass spectrometry
Lundell, Anna-Carin, Ryberg, Henrik, Vandenput, Liesbeth, Rudin, Anna, Ohlsson, Claes and Tivesten, Åsa. (2017). Umbilical cord blood androgen levels in girls and boys assessed by gas chromatography-tandem mass spectrometry. The Journal of Steroid Biochemistry and Molecular Biology. 171, pp. 195 - 200. https://doi.org/10.1016/j.jsbmb.2017.03.022
Increased adipose tissue aromatase activity improves insulin sensitivity and reduces adipose tissue inflammation in male mice
Ohlsson, Claes, Hammarstedt, Ann, Vandenput, Liesbeth, Saarinen, Niina, Ryberg, Henrik, Windahl, Sara H., Farman, Helen H., Jansson, John-Olov, Movérare-Skrtic, Sofia, Smith, Ulf, Zhang, Fu-Ping, Poutanen, Matti, Hedjazifar, Shahram and Sjögren, Klara. (2017). Increased adipose tissue aromatase activity improves insulin sensitivity and reduces adipose tissue inflammation in male mice. American Journal of Physiology - Endocrinology and Metabolism. 313(4), pp. E450 - E462. https://doi.org/10.1152/ajpendo.00093.2017
Low testosterone, but not estradiol, is associated with incident falls in older men: The international MrOS study
Vandenput, Liesbeth, Mellström, Dan, Laughlin, Gail A., Cawthon, Peggy M., Cauley, Jane A., Hoffman, Andrew R., Karlsson, Magnus K., Rosengren, Björn E., Ljunggren, Östen, Nethander, Maria, Eriksson, Anna L., Lorentzon, Mattias, Leung, Jason, Kwok, Timothy, Orwoll, Eric S. and Ohlsson, Claes. (2017). Low testosterone, but not estradiol, is associated with incident falls in older men: The international MrOS study. Journal of Bone and Mineral Research. 32(6), pp. 1174 - 1181. https://doi.org/10.1002/jbmr.3088
Low-frequency synonymous coding variation in CYP2R1 has large effects on vitamin d levels and risk of multiple sclerosis
Manousaki, Despoina, Dudding, Tom, Haworth, Simon, Hsu, Yi-Hsiang, Liu, Chiang-Ti, Medina-Gómez, Carolina, Voortman, Trudy, van der Velde, Nathalie, Melhus, Håkan, 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., ... Richards, J. Brent. (2017). Low-frequency synonymous coding variation in CYP2R1 has large effects on vitamin d levels and risk of multiple sclerosis. American Journal of Human Genetics. 101(2), pp. 227 - 238. https://doi.org/10.1016/j.ajhg.2017.06.014
Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis
Eriksson, Joel, Haring, Robin, Grarup, Niels, Vandenput, Liesbeth, Wallaschofski, Henri, Lorentzen, Erik, Hansen, Torben, Mellström, Dan, Pedersen, Oluf, Nauck, Matthias, Lorentzon, Mattias, Husemoen, Lise Lotte Nystrup, Völzke, Henry, Karlsson, Magnus, Baumeister, Sebastian E., Linneberg, Allan and Ohlsson, Claes. (2017). Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis. PLoS ONE. 12(4), pp. 1 - 15. https://doi.org/10.1371/journal.pone.0176277
Low serum DHEAS predicts increased fracture risk in older men: The MrOS Sweden study
Ohlsson, Claes, Nethander, Maria, Kindmark, Andreas, Ljunggren, Östen, Lorentzon, Mattias, Rosengren, Björn E., Karlsson, Magnus K., Mellström, Dan and Vandenput, Liesbeth. (2017). Low serum DHEAS predicts increased fracture risk in older men: The MrOS Sweden study. Journal of Bone and Mineral Research. 32(8), pp. 1607 - 1614. https://doi.org/10.1002/jbmr.3123
New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
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., ... Loos, Ruth J. F.. (2016). New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk. Nature Communications. 7, p. Article 10495. https://doi.org/10.1038/ncomms10495
A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
Ried, Janina S., Jeff, Janina, Chu, Audrey Y., Bragg-Gresham, Jennifer L., van Dongen, Jenny, Huffman, Jennifer E., Ahluwalia, Tarunveer S., Cadby, Gemma, Eklund, Niina, Eriksson, Joel, Esko, Tõnu, Feitosa, Mary F., Goel, Anuj, Gorski, Mathias, Hayward, Caroline, Heard-Costa, Nancy L., Jackson, Anne U., Jokinen, Eero, Kanoni, Stavroula, ... Loos, Ruth J. F.. (2016). A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape. Nature Communications. 7(1), pp. 1 - 11. https://doi.org/10.1038/ncomms13357
High serum SHBG predicts incident vertebral fractures in elderly men
Vandenput, Liesbeth, Mellström, Dan, Kindmark, Andreas, Johansson, Helena, Lorentzon, Mattias, Leung, Jason, Redlund-Johnell, Inga, Rosengren, Björn E., Karlsson, Magnus K., Wang, Yi-Xiang, Kwok, Timothy and Ohlsson, Claes. (2016). High serum SHBG predicts incident vertebral fractures in elderly men. Journal of Bone and Mineral Research. 31(3), pp. 683 - 689. https://doi.org/10.1002/jbmr.2718
Novel genetic variants associated with increased vertebral volumetric BMD, reduced vertebral fracture risk, and increased expression of SLC1A3 and EPHB2
Nielson, Carrie M., Liu, Ching-Ti, Smith, Albert V., Ackert-Bicknell, Cheryl L., Reppe, Sjur, Jakobsdottir, Johanna, Wassel, Christina, Register, Thomas C., Oei, Ling, Alonso, Nerea, Oei, Edwin H., Parimi, Neeta, Samelson, Elizabeth J., Nalls, Mike A., Zmuda, Joseph, Lang, Thomas, Bouxsein, Mary, Latourelle, Jeanne, Claussnitzer, Melina, ... Hsu, Yi-Hsiang. (2016). Novel genetic variants associated with increased vertebral volumetric BMD, reduced vertebral fracture risk, and increased expression of SLC1A3 and EPHB2. Journal of Bone and Mineral Research. 31(12), pp. 2085 - 2097. https://doi.org/10.1002/jbmr.2913
The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study
Winkler, T.W., Justice, A.E., Graff, M., Barata, Llilda, Feitosa, M.F., Chu, Su, Czajkowski, Jacek, Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Yingchang, Mägi, R., Mihailov, E., Lorentzon, Karl Mattias, Vandenput, Liesbeth and et. al.. (2015). The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study. PLoS Genetics. 11(10), pp. 1-42. https://doi.org/10.1371/journal.pgen.1005378
Genetic studies of body mass index yield new insights for obesity biology
Locke, A, Bratati, K, Berndt, S, Justice, A, Pers, T, Day, F, Powell, C, Vedantam, Buchkovich, M, Vandenput, Liesbeth and et al. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature. 518(7538), pp. 197-206. https://doi.org/10.1038/nature14177
Hydroxysteroid (17 beta)-dehydrogenase 1–deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production
Hakkarainen, Janne, Jokela, Heli, Pakarinen, Pirjo, Heikelä, Hanna, Kätkänaho, Laura, Vandenput, Liesbeth, Ohlsson, Claes, Zhang, Fu-Ping and Poutanen, Matti. (2015). Hydroxysteroid (17 beta)-dehydrogenase 1–deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production. The FASEB Journal. 29(9), pp. 3806 - 3816. https://doi.org/10.1096/fj.14-269035
Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry
Nilsson, Maria E., Vandenput, Liesbeth, Tivesten, Åsa, Norlén, Anna-Karin, Lagerquist, Marie K., Windahl, Sara H., Börjesson, Anna E., Farman, Helen H., Poutannen, Matti, Benrick, Anna, Maliqueo, Manuel, Stener-Victorin, Elisabet, Ryberg, Henrik and Ohlsson, Claes. (2015). Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry. Endocrinology. 156(7), pp. 2492 - 2502. https://doi.org/10.1210/en.2014-1890
Sleep duration and disturbances were associated with testosterone level, muscle mass, and muscle strength - A cross-sectional study in 1274 older men
Auyeung, Tung Wai, Kwok, Tung Wai, Leung, Jason, Shun Wah Lee, Jenny, Ohlsson, Claes, Vandenput, Liesbeth, Wing, Yun Kwok and Woo, Jean. (2015). Sleep duration and disturbances were associated with testosterone level, muscle mass, and muscle strength - A cross-sectional study in 1274 older men. Journal of the American Medical Directors Association (JAMDA). 16(7), pp. 630.e1 - 630.e6. https://doi.org/10.1016/j.jamda.2015.04.006
Limited clinical utility of a genetic risk score for the prediction of fracture risk in elderly subjects
Eriksson, Joel, Evans, Daniel S., Nielson, Carrie M., Shen, Jian, Srikanth, Priya, Hochberg, Marc, McWeeney, Shannon, Cawthon, Peggy M., Wilmot, Beth, Zmuda, Joseph, Tranah, Greg, Mirel, Daniel B., Challa, Sashi, Mooney, Michael, Crenshaw, Andrew, Karlsson, Magnus, Mellström, Dan, Vandenput, Liesbeth, Orwoll, Eric and Ohlsson, Claes. (2015). Limited clinical utility of a genetic risk score for the prediction of fracture risk in elderly subjects. Journal of Bone and Mineral Research. 30(1), pp. 184 - 194. https://doi.org/10.1002/jbmr.2314
Sex steroid actions in male bone
Vanderschueren, Dirk, Laurent, Michaël R., Claessens, Frank, Gielen, Evelien, Lagerquist, Marie K., Vandenput, Liesbeth, Börjesson, Anna E. and Ohlsson, Claes. (2014). Sex steroid actions in male bone. Endocrine Reviews. 35(6), pp. 906-960. https://doi.org/10.1210/er.2014-1024
Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus
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Serum estradiol levels are inversely associated with cortical porosity in older men
Vandenput, Liesbeth, Lorentzon, Mattias, Sundh, Daniel, Nilsson, Maria E., Karlsson, Magnus K., Mellström, Dan and Ohlsson, Claes. (2014). Serum estradiol levels are inversely associated with cortical porosity in older men. The Journal of Clinical Endocrinology and Metabolism. 99(7), pp. E1322 - E1326. https://doi.org/10.1210/jc.2014-1319
Serum estradiol associates with blood hemoglobin in elderly men: The MrOS Sweden study
Lewerin, Catharina, Nilsson-Ehle, Herman, Jacobsson, Stefan, Johansson, Helena, Sundh, Valter, Karlsson, Magnus K., Lorentzon, Mattias, Barrett-Connor, Elizabeth, Vandenput, Liesbeth, Ohlsson, Claes and Mellström, Dan. (2014). Serum estradiol associates with blood hemoglobin in elderly men: The MrOS Sweden study. The Journal of Clinical Endocrinology and Metabolism. 99(7), pp. 2549 - 2556. https://doi.org/10.1210/jc.2013-4111
Genome-wide association studies on serum sex steroid levels
Vandenput, Liesbeth and Ohlsson, Claes. (2014). Genome-wide association studies on serum sex steroid levels. Molecular and Cellular Endocrinology. 382(1), pp. 758 - 766. https://doi.org/10.1016/j.mce.2013.03.009
Does bone resorption stimulate periosteal expansion? A cross-sectional analysis of β-C-telopeptides of type i collagen (CTX), genetic markers of the RANKL pathway, and periosteal circumference as measured by pQCT
Kemp, John P., Sayers, Adrian, Paternoster, Lavinia, Evans, David M., Deere, Kevin, St. Pourcain, Beate, Timpson, Nicholas J., Ring, Susan M., Lorentzon, Mattias, Lehtimäki, Terho, Eriksson, Joel, Kähönen, Mika, Raitakari, Olli, Laaksonen, Marika, Sievänen, Harri, Viikari, Jorma, Lyytikäinen, Leo-Pekka, Smith, George Davey, Fraser, William D., ... Tobias, Jon H.. (2014). Does bone resorption stimulate periosteal expansion? A cross-sectional analysis of β-C-telopeptides of type i collagen (CTX), genetic markers of the RANKL pathway, and periosteal circumference as measured by pQCT. Journal of Bone and Mineral Research. 29(4), pp. 1015 - 1024. https://doi.org/10.1002/jbmr.2093
Dehydroepiandrosterone and its sulfate predict the 5-year risk of coronary heart disease events in elderly men
Tivesten, Åsa, Vandenput, Liesbeth, Carlzon, Daniel, Nilsson, Maria, Karlsson, Magnus K., Ljunggren, Östen, Barrett-Connor, Elizabeth, Mellström, Dan and Ohlsson, Claes. (2014). Dehydroepiandrosterone and its sulfate predict the 5-year risk of coronary heart disease events in elderly men. Journal of the American College of Cardiology. 64(17), pp. 1801 - 1810. https://doi.org/10.1016/j.jacc.2014.05.076
Genetics of endocrine disorders in the era of genome-wide association studies
Vandenput, Liesbeth and Ohlsson, Claes. (2014). Genetics of endocrine disorders in the era of genome-wide association studies. Molecular and Cellular Endocrinology. 382(1), pp. 725 - 725. https://doi.org/10.1016/j.mce.2013.06.031
Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels
Kwan, Johnny S. H., Hsu, Yi-Hsiang, Cheung, Ching-Lung, Dupuis, Josée, Saint-Pierre, Aude, Eriksson, Joel, Handelman, Samuel K., Aragaki, Aaron K., Karasik, David, Pramstaller, Peter P., Kooperberg, Charles, Lacroix, Andrea Z., Larson, Martin G., Lau, Kam-Shing, Lorentzon, Mattias, Pichler, Irene, Sham, Pak Chung, Taliun, Daniel, Vandenput, Liesbeth, ... Kung, Annie Wai Chee. (2014). Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels. Human Molecular Genetics. 23(24), pp. 6684 - 6693. https://doi.org/10.1093/hmg/ddu386
Causal relationship between obesity and vitamin d status : Bi-directional mendelian randomization analysis of multiple cohorts
Vimaleswaran, Karani, Berry, Diane, Lu, Chen, Tikkanen, E., Pilz, Stefan, Hiraki, Linda, Cooper, Jason, Dastani, Zari, Li, Rui, Houston, Denise, Wood, Andrew, Michaelsson, Karl, Vandenput, Liesbeth, Lorentzon, Karl Mattias, Zgaga, Lina, Yerges-Armstrong, Laura, McCarthy, Mark I., Dupuis, Josee, Kaakinen, Marika, ... al, et. (2013). Causal relationship between obesity and vitamin d status : Bi-directional mendelian randomization analysis of multiple cohorts. PLoS Medicine. 10(2), pp. 1-13. https://doi.org/10.1371/journal.pmed.1001383
Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
Berndt, Sonja I., Gustafsson, Stefan, Mägi, Reedik, Ganna, Andrea, Wheeler, Eleanor, Feitosa, Mary F., Justice, Anne E., Monda, Keri L., Croteau-Chonka, Damien C., Day, Felix R., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gentilini, Davide, Jackson, Anne U., Luan, Jianan, Randall, Joshua C., Vedantam, Sailaja, Willer, Cristen J., ... Lorentzon, Mattias. (2013). Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nature Genetics. 45, pp. 501 - 512. https://doi.org/10.1038/ng.2606
Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men
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Assessment of gene-by-sex interaction effect on bone mineral density
Liu, Ching-Ti, Estrada, Karol, Yerges-Armstrong, Laura, Amin, Najaf, Evangelou, Evangelos, Li, Guo, Minster, Ryan L., Carless, Melanie, Kammerer, Candace M., Oei, Ling, Zhou, Yanhua, Alonso, Nerea, Vandenput, Liesbeth, Lorentzon, Karl Mattias, Dailiana, Zoe, Eriksson, Joel, Garcia-Giralt, Natalia, Giroux, Sylvie, Husted, Lise Bjerre, ... al, et. (2012). Assessment of gene-by-sex interaction effect on bone mineral density. Journal of Bone and Mineral Research. 27(10), pp. 2051-2064. https://doi.org/10.1002/jbmr.1679
A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation
Coviello, A.D., Haring, Robin, Wellons, Melissa, Vaidya, Dhananjay, Lehtimaki, Terho, Keildson, S., Lunetta, Kathryn, He, Chunyan, Fornage, Myriam, Lagou, Vasiliki, Mangino, Massimo, Onland-Moret, N. Charlotte, Vandenput, Liesbeth, Lorentzon, Karl Mattias and et. al.. (2012). A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation. PLoS Genetics. 8(7), pp. 1-12. https://doi.org/10.1371/journal.pgen.1002805
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
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., ... Rivadeneira, Fernando. (2012). Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature Genetics. 44(5), pp. 491-503. https://doi.org/10.1038/ng.2249
WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk
Zheng, Hou-Feng, Tobias, Jon H., Duncan, Emma, Evans, David M., Eriksson, Joel, Paternoster, Lavinia, Yerges-Armstrong, Laura M., Lehtimäki, Terho, Bergström, Ulrica, Kähönen, Mika, Leo, Paul J., Raitakari, Olli, Laaksonen, Marika, Nicholson, Geoffrey C., Viikari, Jorma, Ladouceur, Martin, Lehtimäki, Leo-Pekka, Medina-Gomez, Carolina, Rivadeneira, Fernando, ... Lorentzon, Mattias. (2012). WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. PLoS Genetics. 8(7), pp. 1 - 13. https://doi.org/10.1371/journal.pgen.1002745
The role of IGF-1 for fracture risk in men
Vandenput, Liesbeth, Sjögren, Klara, Svensson, Johan and Ohlsson, Claes. (2012). The role of IGF-1 for fracture risk in men. Frontiers in Endocrinology. 3, pp. 1 - 3. https://doi.org/10.3389/fendo.2012.00051
Sex steroids and bone health in men
Ohlsson, Claes, Börjesson, Anna E. and Vandenput, Liesbeth. (2012). Sex steroids and bone health in men. BoneKEy Reports. 1(2), pp. 1 - 7. https://doi.org/10.1038/bonekey.2012.3
Sex steroids and bone health in older Chinese men
Woo, J., Kwok, T., Leung, J. C. S., Ohlsson, C., Vandenput, L. and Leung, P. C.. (2012). Sex steroids and bone health in older Chinese men. Osteoporosis International. 23(5), pp. 1553 - 1562. https://doi.org/10.1007/s00198-011-1552-y
Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus
Medina-Gomez, Carolina, Kemp, John P., Estrada, Karol, Eriksson, Joel, Liu, Jeff, Reppe, Sjur, Evans, David M., Heppe, Denise H. M., Vandenput, Liesbeth, Herrera, Lizbeth, Ring, Susan M., Kruithof, Claudia J., Timpson, Nicholas J., Zillikens, M. Carola, Olstad, Ole K., Zheng, Hou-Feng, Richards, J. Brent, St. Pourcain, Beate, Hofman, Albert, ... Rivadeneira, Fernando. (2012). Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus. PLoS Genetics. 8(7), pp. 1 - 14. https://doi.org/10.1371/journal.pgen.1002718
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile
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Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms
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