Novel genetic variants associated with increased vertebral volumetric BMD, reduced vertebral fracture risk, and increased expression of SLC1A3 and EPHB2

Journal article

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
AuthorsNielson, 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, Siggeirsdottir, Kristin, Srikanth, Priya, Lorentzen, Erik, Vandenput, Liesbeth, Langefeld, Carl D., Raffield, Laura, Terry, Greg, Cox, Amanda J., Allison, Matthew A., Criqui, Michael H., Bowden, Don, Ikram, M. Arfan, Mellström, Dan, Karlsson, Magnus K., Carr, John, Budoff, Matthew, Phillips, Caroline, Cupples, L. Adrienne, Chou, Wen-Chi, Myers, Richard H., Ralston, Stuart H., Gautvik, Kaare M., Cawthon, Peggy M., Cummings, Steven, Karasik, David, Rivadeneira, Fernando, Gudnason, Vilmundur, Orwoll, Eric S., Harris, Tamara B., Ohlsson, Claes, Kiel, Douglas P. and Hsu, Yi-Hsiang
Abstract

Genome‐wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta‐analysis (n  = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta‐analyses to determine associations with morphometric vertebral fracture (n  = 21,701) and clinical vertebral fracture (n  = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD‐associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40 ; 8q24, containing TNFRSF11B ; and 13q14, containing AKAP11 and TNFSF11 . Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (β = 0.22, p  = 1.9 × 10–8) and decreased risk of radiographic vertebral fracture (odds ratio [OR] = 0.75; false discovery rate [FDR] p  = 0.01). In 1p36.12, rs12742784 (MAF = 21%) was associated with higher vBMD (β = 0.09, p  = 1.2 × 10–10) and decreased risk of clinical vertebral fracture (OR = 0.82; FDR p  = 7.4 × 10–4). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β = 0.28, FDR p  = 0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β = 0.12, FDR p  = 1.7 × 10–3, functions in bone‐related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. © 2016 American Society for Bone and Mineral Research.

Keywordsbone QCT/mCT; analysis/quantitation of bone; osteoporosis; diseases and disorders of/related to bone; generalpopulation studies; epidemiology; human association studies; genetic research; fracture risk assessment
Year2016
JournalJournal of Bone and Mineral Research
Journal citation31 (12), pp. 2085 - 2097
PublisherWiley-Blackwell Publishing, Inc.
ISSN0884-0431
Digital Object Identifier (DOI)https://doi.org/10.1002/jbmr.2913
Scopus EID2-s2.0-84992603238
Page range2085 - 2097
Research GroupMary MacKillop Institute for Health Research
Publisher's version
File Access Level
Controlled
Place of publicationUnited States of America
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Evidence of a causal effect of estradiol on fracture risk in men
Nethander, Maria, Vandenput, Liesbeth, Eriksson, Anna L., Windahl, Sara, Funck-Brentano, Thomas and Ohlsson, Claes. (2019). Evidence of a causal effect of estradiol on fracture risk in men. The Journal of Clinical Endocrinology and Metabolism. 104(2), pp. 433 - 442. https://doi.org/10.1210/jc.2018-00934
Meta-analysis of genomewide association studies reveals genetic variants for hip bone geometry
Hsu, Yi-Hsiang, Estrada, Karol, Evangelou, Evangelos, Ackert-Bicknell, Cheryl, Åkesson, Kristina, Beck, Thomas, Brown, Suzanne J., Capellini, Terence, Carbone, Laura, Cauley, Jane, Cheung, Ching-Lung, Cummings, Steven R., Czerwinski, Stefan, Demissie, Serkalem, Econs, Michael J., Evans, Daniel S., Farber, Charles, Gautvik, Kaare M., Harris, Tamara, ... Karasik, David. (2019). Meta-analysis of genomewide association studies reveals genetic variants for hip bone geometry. Journal of Bone and Mineral Research. 34(7), pp. 1284 - 1296. https://doi.org/10.1002/jbmr.3698
The gut microbiota is a major regulator of androgen metabolism in intestinal contents
Colldén, Hannah, Landin, Andreas, Wallenius, Ville, Elebring, Erik, Fändriks, Lars, Nilsson, Maria E., Ryberg, Henrik, Poutanen, Matti, Sjögren, Klara, Vandenput, Liesbeth and Ohlsson, Claes. (2019). The gut microbiota is a major regulator of androgen metabolism in intestinal contents. American Journal of Physiology - Endocrinology and Metabolism. 317(6), pp. E1182 - E1192. https://doi.org/10.1152/ajpendo.00338.2019
Pubertal timing and adult fracture risk in men: A population-based cohort study
Vandenput, Liesbeth, Kindblom, Jenny M., Bygdell, Maria, Nethander, Maria and Ohlsson, Claes. (2019). Pubertal timing and adult fracture risk in men: A population-based cohort study. PLoS Medicine. 16(12), pp. 1 - 14. https://doi.org/10.1371/journal.pmed.1002986
Genome analyses of > 200,000 individuals identify 58 loci for chronic inflammation and highlight pathways that link inflammation and complex disorders
Vaez, Ahmad, Võsa, Urmo, Stathopoulou, Maria G., de Vries, Paul S., Prins, Bram P., Van der Most, Peter J., Tanaka, Toshiko, Naderi, Elnaz, Rose, Lynda M., Wu, Ying, Karlsson, Robert, Barbalic, Maja, Lin, Honghuang, Pool, René, Zhu, Gu, Macé, Aurélien, Sidore, Carlo, Trompet, Stella, Mangino, Massimo, ... Alizadeh, Behrooz Z.. (2018). Genome analyses of > 200,000 individuals identify 58 loci for chronic inflammation and highlight pathways that link inflammation and complex disorders. American Journal of Human Genetics. 103(5), pp. 691-706. https://doi.org/10.1016/j.ajhg.2018.09.009
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
Eriksson, Anna L., Perry, John R. B., Coviello, Andreas D., Delgado, Graciela E., Ferrucci, Luigi, Hoffman, Andrew R., Huhtaniemi, Ilpo T., Ikram, M. Arfan, Karlsson, Magnus K., Kleber, Marcus E., Laughlin, Gail A., Liu, Yongmei, Lorentzon, Mattias, Lunetta, Kathryn L., Mellström, Dan, Murabito, Joanne M., Murray, Anna, Nethander, Maria, Nielson, Carrie M., ... Ohlsson, Claes. (2018). Genetic determinants of circulating estrogen levels and evidence of a causal effect of estradiol on bone density in men. The Journal of Clinical Endocrinology and Metabolism. 103(3), pp. 991 - 1004. https://doi.org/10.1210/jc.2017-02060
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
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, Zoltán, Luan, Jian'an, Malkin, Ida, Ried, Janina S., Smith, Albert V., Thorleifsson, Gudmar, Vandenput, Liesbeth, Zhao, Jing Hua, Zhang, Weihua, ... Boehnke, Michael. (2017). Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nature Communications. 8(1), pp. 1 - 13. https://doi.org/10.1038/s41467-017-00031-7
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
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
Oei, Ling, Estrada, Karol, Duncan, Emma L., Christiansen, Claus, Liu, Ching-Ti, Langdahl, Bente L., Obermayer-Pietsch, Barbara, Riancho, José A., Prince, Richard L., van Schoor, Natasja M., McCloskey, Eugene, Hsu, Yi-Hsiang, Evangelou, Evangelos, Ntzani, Evangelia, Evans, David M., Alonso, Nerea, Husted, Lise B., Valero, Carmen, Hernandez, Jose L., ... Rivadeneira, Fernando. (2014). Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus. Bone. 59, pp. 20 - 27. https://doi.org/10.1016/j.bone.2013.10.015
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
Paternoster, Lavinia, Lorentzon, Mattias, Lehtimäki, Terho, Eriksson, Joel, Kähönen, Mika, Raitakari, Olli, Laaksonen, Marika, Sievänen, Harri, Viikari, Jorma, Lyytikäinen, Leo-Pekka, Mellström, Dan, Karlsson, Magnus, Ljunggren, Östen, Grundberg, Elin, Kemp, John P., Sayers, Adrian, Nethander, Maria, Evans, David M., Vandenput, Liesbeth, ... Ohlsson, Claes. (2013). Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure. PLoS Genetics. 9(2), pp. 1 - 15. https://doi.org/10.1371/journal.pgen.1003247
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
Ohlsson, Claes, Nilsson, Maria E., Tivesten, Åsa, Ryberg, Henrik, Mellström, Dan, Karlsson, Magnus K., Ljunggren, Östen, Labrie, Fernand, Orwoll, Eric S., Lee, David M., Pye, Stephen R., O'Neill, Terence W., Finn, Joseph D., Adams, Judith E., Ward, Kate A., Boonen, Steven, Bartfai, Gyorgy, Casanueva, Felipe F., Forti, Gianni, ... EMAS Study Group. (2013). Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men. The Journal of Clinical Endocrinology and Metabolism. 98(6), pp. e1097 - e1102. https://doi.org/10.1210/jc.2012-3861
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
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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
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