Unraveling the directional link between adiposity and inflammation: a bidirectional mendelian randomization approach

Welsh, P. et al. (2010) Unraveling the directional link between adiposity and inflammation: a bidirectional mendelian randomization approach. Journal of Clinical Endocrinology and Metabolism, 95(1), pp. 93-99. (doi:10.1210/jc.2009-1064)

[img] Text
25916.pdf

117kB

Abstract

<b>Context</b>: Associations between adiposity and circulating inflammation markers are assumed to be causal, although the direction of the relationship has not been proven. <b>Objective</b>: The aim of the study was to explore the causal direction of the relationship between adiposity and inflammation using a bidirectional Mendelian randomization approach. <b>Methods</b>: In the PROSPER study of 5804 elderly patients, we related C-reactive protein (CRP) single nucleotide polymorphisms (SNPs) (rs1800947 and rs1205) and adiposity SNPs (FTO and MC4R) to body mass index (BMI) as well as circulating levels of CRP and leptin. We gave each individual two allele scores ranging from zero to 4, counting each pair of alleles related to CRP levels or BMI. <b>Results</b>: With increasing CRP allele score, there was a stepwise decrease in CRP levels (P for trend < 0.0001) and a 1.98 mg/liter difference between extremes of the allele score distribution, but there was no associated change in BMI or leptin levels (P ≥ 0.89). By contrast, adiposity allele score was associated with 1) an increase in BMI (1.2 kg/m2 difference between extremes; P for trend 0.002); 2) an increase in circulating leptin (5.77 ng/ml difference between extremes; P for trend 0.0027); and 3) increased CRP levels (1.24 mg/liter difference between extremes; P for trend 0.002). <b>Conclusions</b>: Greater adiposity conferred by FTO and MC4R SNPs led to higher CRP levels, with no evidence for any reverse pathway. Future studies should extend our findings to other circulating inflammatory parameters. This study illustrates the potential power of Mendelian randomization to dissect directions of causality between intercorrelated metabolic factors.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macfarlane, Professor Peter and Welsh, Dr Paul and Robertson, Mrs Michele and Stott J, Professor David and Ford, Professor Ian and Shepherd, Prof James and Packard, Professor Chris and Sattar, Professor Naveed
Authors: Welsh, P., Polisecki, E., Robertson, M., Jahn, S., Buckley, B.M., de Craen, A.J.M., Ford, I., Jukema, J.W., Macfarlane, P.W., Packard, C.J., Stott, D.J., Westendorp, R.G.J., Shepherd, J., Hingorani, A.D., Smith, G.Y., Schaefer, E., and Sattar, N.A.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Clinical Endocrinology and Metabolism
Publisher:The Endocrine Society
ISSN:0021-972X
ISSN (Online):1945-7197
Published Online:11 November 2009
Copyright Holders:Copyright © 2010 The Endocrine Society
First Published:First published in Journal of Clinical Endocrinology and Metabolism 95(1):93-99
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record