Functional characterisation of ADIPOQ variants using individuals recruited by genotype.
Molecular and Cellular Endocrinology
© 2016 Elsevier Ireland Ltd. All rights reserved.
Reason for embargo
Four non-coding GWAS variants in or near the ADIPOQ gene (rs17300539, rs17366653, rs3821799 and rs56354395) together explain 4% of the variation in circulating adiponectin. The functional basis for this is unknown. We tested the effect of these variants on ADIPOQ transcription, splicing and stability respectively in adipose tissue samples from participants recruited by rs17366653 genotype. Transcripts carrying rs17300539 demonstrated a 17% increase in expression (p = 0.001). Variant rs17366653 was associated with disruption of ADIPOQ splicing leading to a 7 fold increase in levels of a non-functional transcript (p = 0.002). Transcripts carrying rs56354395 demonstrated a 59% decrease in expression (p = <0.0001). No effects of rs3821799 genotype on expression was observed. Association between variation in the ADIPOQ gene and serum adiponectin may arise from effects on mRNA transcription, splicing or stability. These studies illustrate the utility of recruit-by-genotype studies in relevant human tissues in functional interpretation of GWAS signals.
The work was supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the UK National Health Service, NIHR or the UK Department of Health. The authors acknowledge Diabetes UK for funding (grant number 12/0004470).
This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.
Vol. 428, pp. 49 - 57
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