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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Fältnamn	Indikatorer	Metadata
000		09556naa a2201597 4500
001		oai:gup.ub.gu.se/161244
003		SwePub
008		240528s2012 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:lup.lub.lu.se:609e539b-1012-40ad-b9c6-35ecbfa9f16c
009		oai:DiVA.org:uu-181141
024	7	a https://gup.ub.gu.se/publication/1612442 URI
024	7	a https://doi.org/10.1371/journal.pgen.10028052 DOI
024	7	a https://lup.lub.lu.se/record/30732192 URI
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1811412 URI
040		a (SwePub)gud (SwePub)lud (SwePub)uu
041		a eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Coviello, Andrea D4 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 regulation.
264		c 2012-07-19
264	1	b Public Library of Science (PLoS),c 2012
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=1.8×10(-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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Ortopedi0 (SwePub)302112 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Orthopaedics0 (SwePub)302112 hsv//eng
700	1	a Haring, Robin4 aut
700	1	a Wellons, Melissa4 aut
700	1	a Vaidya, Dhananjay4 aut
700	1	a Lehtimäki, Terho4 aut
700	1	a Keildson, Sarah4 aut
700	1	a Lunetta, Kathryn L4 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, Joelu Gothenburg University,Göteborgs universitet,Institutionen för medicin,Centre for Bone and Arthritis Research,Institute of Medicine4 aut0 (Swepub:gu)xerjoe
700	1	a Garcia, Melissa4 aut
700	1	a Liu, Yong Mei4 aut
700	1	a Koster, Annemarie4 aut
700	1	a Lohman, Kurt4 aut
700	1	a Lyytikäinen, 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, Liesbeth,d 1974u Gothenburg University,Göteborgs universitet,Institutionen för medicin,Centre for Bone and Arthritis Research,Institute of Medicine4 aut0 (Swepub:gu)xvanli
700	1	a Wood, Andrew R4 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 G4 aut
700	1	a Chen, Yuhui4 aut
700	1	a Cummings, Steven4 aut
700	1	a Ferrucci, Luigi4 aut
700	1	a Gunter, Marc J4 aut
700	1	a Hankinson, Susan E4 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-Olov,d 1954u Gothenburg University,Göteborgs universitet,Institutionen för medicin,Centre for Bone and Arthritis Research,Institute of Medicine4 aut0 (Swepub:gu)xjanjo
700	1	a Johnson, Andrew D4 aut
700	1	a Karasik, David4 aut
700	1	a Karlsson, Magnusu Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups4 aut0 (Swepub:lu)orto-mka
700	1	a Kettunen, Johannes4 aut
700	1	a Kiel, Douglas P4 aut
700	1	a Kraft, Peter4 aut
700	1	a Liu, Jingmin4 aut
700	1	a Ljunggren, Östenu Uppsala universitet,Metabola bensjukdomar4 aut0 (Swepub:uu)osteljun
700	1	a Lorentzon, Mattias,d 1970u Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine4 aut0 (Swepub:gu)xlomat
700	1	a Maggio, Marcello4 aut
700	1	a Markus, Marcello R P4 aut
700	1	a Mellström, Dan,d 1945u Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine4 aut0 (Swepub:gu)xmelda
700	1	a Miljkovic, Iva4 aut
700	1	a Mirel, Daniel4 aut
700	1	a Nelson, Sarah4 aut
700	1	a Morin Papunen, Laure4 aut
700	1	a Peeters, Petra H M4 aut
700	1	a Prokopenko, Inga4 aut
700	1	a Raffel, Leslie4 aut
700	1	a Reincke, Martin4 aut
700	1	a Reiner, Alex P4 aut
700	1	a Rexrode, Kathryn4 aut
700	1	a Rivadeneira, Fernando4 aut
700	1	a Schwartz, Stephen M4 aut
700	1	a Siscovick, David4 aut
700	1	a Soranzo, Nicole4 aut
700	1	a Stöckl, Doris4 aut
700	1	a Tworoger, Shelley4 aut
700	1	a Uitterlinden, André G4 aut
700	1	a van Gils, Carla H4 aut
700	1	a Vasan, Ramachandran S4 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 J4 aut
700	1	a De Vivo, Immaculata4 aut
700	1	a Harris, Tamara B4 aut
700	1	a Hunter, David J4 aut
700	1	a Kähönen, Mika4 aut
700	1	a Liu, Simin4 aut
700	1	a Ouyang, Pamela4 aut
700	1	a Spector, Tim D4 aut
700	1	a van der Schouw, Yvonne T4 aut
700	1	a Viikari, Jorma4 aut
700	1	a Wallaschofski, Henri4 aut
700	1	a McCarthy, Mark I4 aut
700	1	a Frayling, Timothy M4 aut
700	1	a Murray, Anna4 aut
700	1	a Franks, Steve4 aut
700	1	a Järvelin, Marjo-Riitta4 aut
700	1	a de Jong, Frank H4 aut
700	1	a Raitakari, Olli4 aut
700	1	a Teumer, Alexander4 aut
700	1	a Ohlsson, Claes,d 1965u Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine4 aut0 (Swepub:gu)xohlcl
700	1	a Murabito, Joanne M4 aut
700	1	a Perry, John R B4 aut
710	2	a Göteborgs universitetb Institutionen för medicin4 org
773	0	t PLoS geneticsd : Public Library of Science (PLoS)g 8:7q 8:7x 1553-7404x 1553-7390
856	4	u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002805&type=printable
856	4	u https://portal.research.lu.se/files/2275197/3563301.pdfx primaryx freey FULLTEXT
856	4	u http://dx.doi.org/10.1371/journal.pgen.1002805x freey FULLTEXT
856	4	u https://uu.diva-portal.org/smash/get/diva2:553175/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4 8	u https://gup.ub.gu.se/publication/161244
856	4 8	u https://doi.org/10.1371/journal.pgen.1002805
856	4 8	u https://lup.lub.lu.se/record/3073219
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-181141

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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 ...; and Orthopaedics

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