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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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.

Coviello, Andrea D (author)

Haring, Robin (author)

Wellons, Melissa (author)

Vaidya, Dhananjay (author)

Lehtimäki, Terho (author)

Keildson, Sarah (author)

Lunetta, Kathryn L (author)

He, Chunyan (author)

Fornage, Myriam (author)

Lagou, Vasiliki (author)

Mangino, Massimo (author)

Onland-Moret, N Charlotte (author)

Chen, Brian (author)

Eriksson, Joel (author): Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine

Garcia, Melissa (author)

Liu, Yong Mei (author)

Koster, Annemarie (author)

Lohman, Kurt (author)

Lyytikäinen, Leo-Pekka (author)

Petersen, Ann-Kristin (author)

Prescott, Jennifer (author)

Stolk, Lisette (author)

Vandenput, Liesbeth, 1974 (author): Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine

Wood, Andrew R (author)

Zhuang, Wei Vivian (author)

Ruokonen, Aimo (author)

Hartikainen, Anna-Liisa (author)

Pouta, Anneli (author)

Bandinelli, Stefania (author)

Biffar, Reiner (author)

Brabant, Georg (author)

Cox, David G (author)

Chen, Yuhui (author)

Cummings, Steven (author)

Ferrucci, Luigi (author)

Gunter, Marc J (author)

Hankinson, Susan E (author)

Martikainen, Hannu (author)

Hofman, Albert (author)

Homuth, Georg (author)

Illig, Thomas (author)

Jansson, John-Olov, 1954 (author): Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine

Johnson, Andrew D (author)

Karasik, David (author)

Karlsson, Magnus (author): Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups

Kettunen, Johannes (author)

Kiel, Douglas P (author)

Kraft, Peter (author)

Liu, Jingmin (author)

Ljunggren, Östen (author): Uppsala universitet,Metabola bensjukdomar

Lorentzon, Mattias, 1970 (author): Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine

Maggio, Marcello (author)

Markus, Marcello R P (author)

Mellström, Dan, 1945 (author): Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine

Miljkovic, Iva (author)

Mirel, Daniel (author)

Nelson, Sarah (author)

Morin Papunen, Laure (author)

Peeters, Petra H M (author)

Prokopenko, Inga (author)

Raffel, Leslie (author)

Reincke, Martin (author)

Reiner, Alex P (author)

Rexrode, Kathryn (author)

Rivadeneira, Fernando (author)

Schwartz, Stephen M (author)

Siscovick, David (author)

Soranzo, Nicole (author)

Stöckl, Doris (author)

Tworoger, Shelley (author)

Uitterlinden, André G (author)

van Gils, Carla H (author)

Vasan, Ramachandran S (author)

Wichmann, H-Erich (author)

Zhai, Guangju (author)

Bhasin, Shalender (author)

Bidlingmaier, Martin (author)

Chanock, Stephen J (author)

De Vivo, Immaculata (author)

Harris, Tamara B (author)

Hunter, David J (author)

Kähönen, Mika (author)

Liu, Simin (author)

Ouyang, Pamela (author)

Spector, Tim D (author)

van der Schouw, Yvonne T (author)

Viikari, Jorma (author)

Wallaschofski, Henri (author)

McCarthy, Mark I (author)

Frayling, Timothy M (author)

Murray, Anna (author)

Franks, Steve (author)

Järvelin, Marjo-Riitta (author)

de Jong, Frank H (author)

Raitakari, Olli (author)

Teumer, Alexander (author)

Ohlsson, Claes, 1965 (author): Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine

Murabito, Joanne M (author)

Perry, John R B (author)

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(creator_code:org_t)

2012-07-19
2012
English.
In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7

Related links:: https://journals.plo...; show more...; https://portal.resea... (primary) (free); http://dx.doi.org/10... (free); https://uu.diva-port... (primary) (Raw object); https://gup.ub.gu.se...; https://doi.org/10.1...; https://lup.lub.lu.s...; https://urn.kb.se/re...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4×10(-11)), GCKR (rs780093, 2p23.3, p = 2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5×10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.

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By the author/editor: Coviello, Andrea ...; Haring, Robin; Wellons, Melissa; Vaidya, Dhananja ...; Lehtimäki, Terho; Keildson, Sarah; show more...; Lunetta, Kathryn ...; He, Chunyan; Fornage, Myriam; Lagou, Vasiliki; Mangino, Massimo; Onland-Moret, N ...; Chen, Brian; Eriksson, Joel; Garcia, Melissa; Liu, Yong Mei; Koster, Annemari ...; Lohman, Kurt; Lyytikäinen, Leo ...; Petersen, Ann-Kr ...; Prescott, Jennif ...; Stolk, Lisette; Vandenput, Liesb ...; Wood, Andrew R; Zhuang, Wei Vivi ...; Ruokonen, Aimo; Hartikainen, Ann ...; Pouta, Anneli; Bandinelli, Stef ...; Biffar, Reiner; Brabant, Georg; Cox, David G; Chen, Yuhui; Cummings, Steven; Ferrucci, Luigi; Gunter, Marc J; Hankinson, Susan ...; Martikainen, Han ...; Hofman, Albert; Homuth, Georg; Illig, Thomas; Jansson, John-Ol ...; Johnson, Andrew ...; Karasik, David; Karlsson, Magnus; Kettunen, Johann ...; Kiel, Douglas P; Kraft, Peter; Liu, Jingmin; Ljunggren, Östen; Lorentzon, Matti ...; Maggio, Marcello; Markus, Marcello ...; Mellström, Dan, ...; Miljkovic, Iva; Mirel, Daniel; Nelson, Sarah; Morin Papunen, L ...; Peeters, Petra H ...; Prokopenko, Inga; Raffel, Leslie; Reincke, Martin; Reiner, Alex P; Rexrode, Kathryn; Rivadeneira, Fer ...; Schwartz, Stephe ...; Siscovick, David; Soranzo, Nicole; Stöckl, Doris; Tworoger, Shelle ...; Uitterlinden, An ...; van Gils, Carla ...; Vasan, Ramachand ...; Wichmann, H-Eric ...; Zhai, Guangju; Bhasin, Shalende ...; Bidlingmaier, Ma ...; Chanock, Stephen ...; De Vivo, Immacul ...; Harris, Tamara B; Hunter, David J; Kähönen, Mika; Liu, Simin; Ouyang, Pamela; Spector, Tim D; van der Schouw, ...; Viikari, Jorma; Wallaschofski, H ...; McCarthy, Mark I; Frayling, Timoth ...; Murray, Anna; Franks, Steve; Järvelin, Marjo- ...; de Jong, Frank H; Raitakari, Olli; Teumer, Alexande ...; Ohlsson, Claes, ...; Murabito, Joanne ...; Perry, John R B; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Orthopaedics

Articles in the publication: PLoS genetics

By the university: University of Gothenburg; Lund University; Uppsala University

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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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