@article{a1a577665da445c69f016269c62f3528,
title = "Genetic determinants of circulating estrogen levels and evidence of a causal effect of estradiol on bone density in men",
abstract = "Results: Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 3 1028) and Xq27.3, rs5951794 (P = 3.1 3 10210). E1 signals were found in CYP19A1 (rs2899472, P = 5.5 3 10223), in Tripartite motif containing 4 (TRIM4; rs17277546, P = 5.8 3 10214), and CYP11B1/B2 (rs10093796, P = 1.2 3 1028). E2 signals in CYP19A1 and FAM9B were associated with bone mineral density (BMD). Mendelian randomization analysis suggested a causal effect of serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a 0.048 standard deviation increase in lumbar spine BMD (P = 2.8 3 10212). In men and women combined, CYP19A1 alleles associated with higher E2 levels were associated with lower degrees of insulin resistance. Conclusions: Our findings confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and strengthen the causal importance of E2 for bone health in men. We also report two independent loci on the X-chromosome for E2, and one locus each in TRIM4 and CYP11B1/B2, for E1.",
author = "Eriksson, {Anna L.} and Perry, {John R.B.} and Coviello, {Andrea D.} and Delgado, {Graciela E.} and Luigi Ferrucci and Hoffman, {Andrew R.} and Huhtaniemi, {Ilpo T.} and {Arfan Ikram}, M. and Karlsson, {Magnus K.} and Kleber, {Marcus E.} and Laughlin, {Gail A.} and Yongmei Liu and Mattias Lorentzon and Lunetta, {Kathryn L.} and Dan Mellstr{\"o}m and Murabito, {Joanne M.} and Anna Murray and Maria Nethander and Nielson, {Carrie M.} and Inga Prokopenko and Pye, {Stephen R.} and Raffel, {Leslie J.} and Fernando Rivadeneira and Priya Srikanth and Lisette Stolk and Alexander Teumer and Travison, {Thomas G.} and Uitterlinden, {Andr{\'e} G.} and Dhananjay Vaidya and Dirk Vanderschueren and Zmuda, {Joseph M.} and Winfried M{\"a}rz and Orwoll, {Eric S.} and Pamela Ouyang and Liesbeth Vandenput and Wu, {Frederick C.W.} and {De Jong}, {Frank H.} and Shalender Bhasin and Kiel, {Douglas P.} and Claes Ohlsson",
note = "Funding Information: Financial Support: This work was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA (Avtal om L{\"a}karutbildning och Forskning/L{\"a}karutbildningsavtalet) research grant in Gothenburg, the Lundberg Foundation, Knut and Alice Wallenberg Foundation, the Torsten and Ragnar S{\"o}derberg{\textquoteright}s Foundation, and the Novo Nordisk Foundation. Publisher Copyright: {\textcopyright} 2018 American Society for Engineering Education. All rights reserved.",
year = "2018",
doi = "10.1210/jc.2017-02060",
language = "English (US)",
volume = "103",
pages = "991--1004",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "3",
}