Genome-wide association studies on serum sex steroid levels

Journal article

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
AuthorsVandenput, Liesbeth and Ohlsson, Claes
Abstract

Even though the levels of circulating sex steroid hormones are to a large extent heritable, their genetic determinants are largely unknown. With the advent of genome-wide association studies (GWAS), much progress has been made and several genetic loci have been identified to be associated with serum levels of dehydroepiandrosterone sulfate, testosterone and sex hormone-binding globulin. The variants identified so far only explain a small amount of the overall heritability, but may help to elucidate the role of sex steroid hormones in common disorders such as hypogonadism, type 2 diabetes and hormone-sensitive cancers. This review provides an overview of the current state of knowledge of the genetic determinants of sex steroid hormones, with a focus on recent GWAS and brief directions for elucidating the remaining heritability.

Keywordsgenome-wide association studies; testosterone; estradiol; sex hormone-binding globulin; dehydroepiandrosterone; hypogonadism
Year2014
JournalMolecular and Cellular Endocrinology
Journal citation382 (1), pp. 758 - 766
PublisherElsevier Ireland Ltd.
ISSN0303-7207
Digital Object Identifier (DOI)https://doi.org/10.1016/j.mce.2013.03.009
Scopus EID2-s2.0-84888380305
Page range758 - 766
Research GroupMary MacKillop Institute for Health Research
Publisher's version
File Access Level
Controlled
Place of publicationIreland
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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
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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
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Increased adipose tissue aromatase activity improves insulin sensitivity and reduces adipose tissue inflammation in male mice
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Low testosterone, but not estradiol, is associated with incident falls in older men: The international MrOS study
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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
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Low serum DHEAS predicts increased fracture risk in older men: The MrOS Sweden study
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
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High serum SHBG predicts incident vertebral fractures in elderly men
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The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study
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Genetic studies of body mass index yield new insights for obesity biology
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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
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Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry
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Sleep duration and disturbances were associated with testosterone level, muscle mass, and muscle strength - A cross-sectional study in 1274 older men
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Limited clinical utility of a genetic risk score for the prediction of fracture risk in elderly subjects
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Sex steroid actions in male bone
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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
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Serum estradiol associates with blood hemoglobin in elderly men: The MrOS Sweden study
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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
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Dehydroepiandrosterone and its sulfate predict the 5-year risk of coronary heart disease events in elderly men
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Genetics of endocrine disorders in the era of genome-wide association studies
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Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels
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Causal relationship between obesity and vitamin d status : Bi-directional mendelian randomization analysis of multiple cohorts
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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
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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
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
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WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk
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The role of IGF-1 for fracture risk in men
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Sex steroids and bone health in men
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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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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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Low DHEAS levels are associated with depressive symptoms in elderly Chinese men: results from a large study
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Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study
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Testosterone but not estradiol level is positively related to muscle strength and physical performance independent of muscle mass: a cross-sectional study in 1489 older men
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High serum testosterone is associated with reduced risk of cardiovascular events in elderly men - The MrOS (Osteoporotic Fractures in Men) study in Sweden
Ohlsson, Claes, Barrett-Connor, Elizabeth, Bhasin, Shalender, Orwoll, Eric, Labrie, Fernand, Karlsson, Magnus K., Ljunggren, Östen, Vandenput, Liesbeth, Mellström, Dan and Tivesten, Åsa. (2011). High serum testosterone is associated with reduced risk of cardiovascular events in elderly men - The MrOS (Osteoporotic Fractures in Men) study in Sweden. Journal of the American College of Cardiology. 58(16), pp. 1674 - 1681. https://doi.org/10.1016/j.jacc.2011.07.019