A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone-Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation

doi:10.1371/journal.pgen.1002805

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Fältnamn	Indikatorer	Metadata
000		07611naa a22015493a 4500
001		22094656
003		SE-LIBR
005		20171208151545.0
007		cr\|\|\|\|\|\|\|\|\|\|\|\|
008		171208s2012 sw \|\|\|\| o \|\|\|\| \|\|eng c
024	7	a http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1811412 uri
024	7	a urn:nbn:se:uu:diva-1811412 urn
024	7	a 10.1371/journal.pgen.10028052 doi
040		a S
041	0	a eng
042		9 EPLK
100	1	a Coviello, Andrea D.4 aut
245	1 0	a A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone-Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulationh [Elektronisk resurs]
260		c 2012
500		a Published
506	0	a gratis
520		a 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 = 1.8x10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4x10(-11)), GCKR (rs780093, 2p23.3, p=2.2x10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4x10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1x10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9x10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3x10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5x10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1x10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3x10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7x10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5x10(-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 = 2.5x10(-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 similar to 15.6% and similar to 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.
650	7	a Medical and Health Sciences2 hsv
650	7	a Medicin och hälsovetenskap2 hsv
700	1	a Haring, Robin4 aut
700	1	a Wellons, Melissa4 aut
700	1	a Vaidya, Dhananjay4 aut
700	1	a Lehtimaki, Terho4 aut
700	1	a Keildson, Sarah4 aut
700	1	a Lunetta, Kathryn L.4 aut
700	1	a He, Chunyan4 aut
700	1	a Fornage, Myriam4 aut
700	1	a Lagou, Vasiliki4 aut
700	1	a Mangino, Massimo4 aut
700	1	a Onland-Moret, N. Charlotte4 aut
700	1	a Chen, Brian4 aut
700	1	a Eriksson, Joel4 aut
700	1	a Garcia, Melissa4 aut
700	1	a Mei, Yong4 aut
700	1	a Koster, Annemarie4 aut
700	1	a Lohman, Kurt4 aut
700	1	a Lyytikainen, Leo-Pekka4 aut
700	1	a Petersen, Ann-Kristin4 aut
700	1	a Prescott, Jennifer4 aut
700	1	a Stolk, Lisette4 aut
700	1	a Vandenput, Liesbeth4 aut
700	1	a Wood, Andrew R.4 aut
700	1	a Zhuang, Wei Vivian4 aut
700	1	a Ruokonen, Aimo4 aut
700	1	a Hartikainen, Anna-Liisa4 aut
700	1	a Pouta, Anneli4 aut
700	1	a Bandinelli, Stefania4 aut
700	1	a Biffar, Reiner4 aut
700	1	a Brabant, Georg4 aut
700	1	a Cox, David G.4 aut
700	1	a Chen, Yuhui4 aut
700	1	a Cummings, Steven4 aut
700	1	a Ferrucci, Luigi4 aut
700	1	a Gunter, Marc J.4 aut
700	1	a Hankinson, Susan E.4 aut
700	1	a Martikainen, Hannu4 aut
700	1	a Hofman, Albert4 aut
700	1	a Homuth, Georg4 aut
700	1	a Illig, Thomas4 aut
700	1	a Jansson, John-Olov4 aut
700	1	a Johnson, Andrew D.4 aut
700	1	a Karasik, David4 aut
700	1	a Karlsson, Magnus4 aut
700	1	a Kettunen, Johannes4 aut
700	1	a Kiel, Douglas P.4 aut
700	1	a Kraft, Peter4 aut
700	1	a Liu, Jingmin4 aut
700	1	a Ljunggren, Östen4 aut
700	1	a Lorentzon, Mattias4 aut
700	1	a Maggio, Marcello4 aut
700	1	a Markus, Marcello R. P.4 aut
700	1	a Mellstrom, Dan4 aut
700	1	a Miljkovic, Iva4 aut
700	1	a Mirel, Daniel4 aut
700	1	a Nelson, Sarah4 aut
700	1	a Papunen, Laure Morin4 aut
700	1	a Peeters, Petra H. M.4 aut
700	1	a Prokopenko, Inga4 aut
700	1	a Raffel, Leslie4 aut
700	1	a Reincke, Martin4 aut
700	1	a Reiner, Alex P.4 aut
700	1	a Rexrode, Kathryn4 aut
700	1	a Rivadeneira, Fernando4 aut
700	1	a Schwartz, Stephen M.4 aut
700	1	a Siscovick, David4 aut
700	1	a Soranzo, Nicole4 aut
700	1	a Stockl, Doris4 aut
700	1	a Tworoger, Shelley4 aut
700	1	a Uitterlinden, Andre G.4 aut
700	1	a van Gils, Carla H.4 aut
700	1	a Vasan, Ramachandran S.4 aut
700	1	a Wichmann, H. -Erich4 aut
700	1	a Zhai, Guangju4 aut
700	1	a Bhasin, Shalender4 aut
700	1	a Bidlingmaier, Martin4 aut
700	1	a Chanock, Stephen J.4 aut
700	1	a De Vivo, Immaculata4 aut
700	1	a Harris, Tamara B.4 aut
700	1	a Hunter, David J.4 aut
700	1	a Kahonen, Mika4 aut
700	1	a Liu, Simin4 aut
700	1	a Ouyang, Pamela4 aut
700	1	a Spector, Tim D.4 aut
700	1	a van der Schouw, Yvonne T.4 aut
700	1	a Viikari, Jorma4 aut
700	1	a Wallaschofski, Henri4 aut
700	1	a McCarthy, Mark I.4 aut
700	1	a Frayling, Timothy M.4 aut
700	1	a Murray, Anna4 aut
700	1	a Franks, Steve4 aut
700	1	a Jarvelin, Marjo-Riitta4 aut
700	1	a de Jong, Frank H.4 aut
700	1	a Raitakari, Olli4 aut
700	1	a Teumer, Alexander4 aut
700	1	a Ohlsson, Claes4 aut
700	1	a Murabito, Joanne M.4 aut
700	1	a Perry, John R. B.4 aut
710	1 2	a Uppsala universitetb Medicinska och farmaceutiska vetenskapsområdet4 pbl
772	1 8	i channel recordw 19753896
773	0 8	i Värdpublikationt PLOS Geneticsg 8:7, e1002805x 1553-7390
856	4 0	u http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-181141
856	4 0	u http://dx.doi.org/10.1371/journal.pgen.1002805
856	4 0	u http://uu.diva-portal.org/smash/get/diva2:553175/FULLTEXT01
841		5 APISa x ab 171209\|\|0000\|\|\|\|\|001\|\|\|\|\|\|000000e 1
024	7	5 APISa urn:nbn:se:uu:diva-1811412 urn
852		5 APISb APIS
856	4 0	5 APISu http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-181141

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Av författaren/redakt...: Coviello, Andrea ...; Haring, Robin; Wellons, Melissa; Vaidya, Dhananja ...; Lehtimaki, Terho; Keildson, Sarah; visa fler...; Lunetta, Kathryn ...; He, Chunyan; Fornage, Myriam; Lagou, Vasiliki; Mangino, Massimo; Onland-Moret, N. ...; Chen, Brian; Eriksson, Joel; Garcia, Melissa; Mei, Yong; Koster, Annemari ...; Lohman, Kurt; Lyytikainen, 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 ...; Mellstrom, Dan; Miljkovic, Iva; Mirel, Daniel; Nelson, Sarah; Papunen, Laure M ...; Peeters, Petra H ...; Prokopenko, Inga; Raffel, Leslie; Reincke, Martin; Reiner, Alex P.; Rexrode, Kathryn; Rivadeneira, Fer ...; Schwartz, Stephe ...; Siscovick, David; Soranzo, Nicole; Stockl, Doris; Tworoger, Shelle ...; Uitterlinden, An ...; van Gils, Carla ...; Vasan, Ramachand ...; Wichmann, H. -Er ...; Zhai, Guangju; Bhasin, Shalende ...; Bidlingmaier, Ma ...; Chanock, Stephen ...; De Vivo, Immacul ...; Harris, Tamara B ...; Hunter, David J.; Kahonen, Mika; Liu, Simin; Ouyang, Pamela; Spector, Tim D.; van der Schouw, ...; Viikari, Jorma; Wallaschofski, H ...; McCarthy, Mark I ...; Frayling, Timoth ...; Murray, Anna; Franks, Steve; Jarvelin, Marjo- ...; de Jong, Frank H ...; Raitakari, Olli; Teumer, Alexande ...; Ohlsson, Claes; Murabito, Joanne ...; Perry, John R. B ...; visa färre...

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