Genome-wide association study identifies two novel regions at 11p15.5-p13 and 1p31 with major impact on acute-phase serum amyloid A.
| Title: | Genome-wide association study identifies two novel regions at 11p15.5-p13 and 1p31 with major impact on acute-phase serum amyloid A. |
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| Authors: | Carola Marzi, Eva Albrecht, Pirro G Hysi, Vasiliki Lagou, Melanie Waldenberger, Anke Tönjes, Inga Prokopenko, Katharina Heim, Hannah Blackburn, Janina S Ried, Marcus E Kleber, Massimo Mangino, Barbara Thorand, Annette Peters, Christopher J Hammond, Harald Grallert, Bernhard O Boehm, Peter Kovacs, Ludwig Geistlinger, Holger Prokisch, Bernhard R Winkelmann, Tim D Spector, H-Erich Wichmann, Michael Stumvoll, Nicole Soranzo, Winfried März, Wolfgang Koenig, Thomas Illig, Christian Gieger |
| Source: | PLoS Genetics, Vol 6, Iss 11, p e1001213 (2010) |
| Publisher Information: | Public Library of Science (PLoS), 2010. |
| Publication Year: | 2010 |
| Collection: | LCC:Genetics |
| Subject Terms: | Genetics, QH426-470 |
| More Details: | Elevated levels of acute-phase serum amyloid A (A-SAA) cause amyloidosis and are a risk factor for atherosclerosis and its clinical complications, type 2 diabetes, as well as various malignancies. To investigate the genetic basis of A-SAA levels, we conducted the first genome-wide association study on baseline A-SAA concentrations in three population-based studies (KORA, TwinsUK, Sorbs) and one prospective case cohort study (LURIC), including a total of 4,212 participants of European descent, and identified two novel genetic susceptibility regions at 11p15.5-p13 and 1p31. The region at 11p15.5-p13 (rs4150642; p = 3.20×10(-111)) contains serum amyloid A1 (SAA1) and the adjacent general transcription factor 2 H1 (GTF2H1), Hermansky-Pudlak Syndrome 5 (HPS5), lactate dehydrogenase A (LDHA), and lactate dehydrogenase C (LDHC). This region explains 10.84% of the total variation of A-SAA levels in our data, which makes up 18.37% of the total estimated heritability. The second region encloses the leptin receptor (LEPR) gene at 1p31 (rs12753193; p = 1.22×10(-11)) and has been found to be associated with CRP and fibrinogen in previous studies. Our findings demonstrate a key role of the 11p15.5-p13 region in the regulation of baseline A-SAA levels and provide confirmative evidence of the importance of the 1p31 region for inflammatory processes and the close interplay between A-SAA, leptin, and other acute-phase proteins. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1553-7390 1553-7404 |
| Relation: | http://europepmc.org/articles/PMC2987930?pdf=render; https://doaj.org/toc/1553-7390; https://doaj.org/toc/1553-7404 |
| DOI: | 10.1371/journal.pgen.1001213 |
| Access URL: | https://doaj.org/article/fcb46fa10ab545aca536d41da944fea4 |
| Accession Number: | edsdoj.fcb46fa10ab545aca536d41da944fea4 |
| Database: | Directory of Open Access Journals |
| ISSN: | 15537390 15537404 |
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| DOI: | 10.1371/journal.pgen.1001213 |
| Published in: | PLoS Genetics |
| Language: | English |