Sökning: WFRF:(Terho P.) > A Genome-Wide Assoc...
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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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