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Vitart, V |
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dc.date.accessioned |
2015-07-01T23:49:43Z |
en |
dc.date.issued |
2015 |
en |
dc.identifier.citation |
PLoS One, 2015, 10 (3), pp. e0119752 - e0119752 |
en |
dc.identifier.issn |
1932-6203 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/26111 |
en |
dc.description.abstract |
We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment. |
en |
dc.format.medium |
Electronic-eCollection |
en |
dc.language |
eng |
en |
dc.publisher |
Public Library of Science |
en |
dc.relation.ispartofseries |
PLoS One |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1932-6203/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/publicdomain/zero/1.0/ |
en |
dc.title |
Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1371/journal.pone.0119752 |
en |
pubs.issue |
3 |
en |
pubs.begin-page |
e0119752 |
en |
pubs.volume |
10 |
en |
dc.description.version |
VoR - Version of Record |
en |
dc.identifier.pmid |
25811787 |
en |
pubs.end-page |
e0119752 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Journal Article |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
en |
pubs.subtype |
Research Support, N.I.H., Extramural |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
479388 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
School of Medicine |
en |
pubs.org-id |
Medicine Department |
en |
dc.identifier.eissn |
1932-6203 |
en |
pubs.record-created-at-source-date |
2015-07-02 |
en |
pubs.dimensions-id |
25811787 |
en |