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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/34767
Title: Causal relationship between body mass index and fetuin-A level in the asian population: A bidirectional mendelian randomization study
Authors: Ammarin Thakkinstian
Laor Chailurkit
Daruneewan Warodomwichit
Wipa Ratanachaiwong
Sukit Yamwong
Suwannee Chanprasertyothin
John Attia
Piyamitr Sritara
Boonsong Ongphiphadhanakul
Mahidol University
Medical and Health Office
University of Newcastle Faculty of Medicine and Health Sciences
Keywords: Medicine
Issue Date: 1-Jan-2014
Citation: Clinical Endocrinology. Vol.81, No.2 (2014), 197-203
Abstract: Objective Fetuin-A is associated with body mass index (BMI) as well as components of the metabolic syndrome. However, it is unclear if fetuin-A affects BMI or the other way around. We therefore assessed the causal association between fetuin-A and BMI or vice versa, utilizing a bidirectional Mendelian randomization approach. Design and Methods This was a study of 2558 subjects from the Electricity Generating Authority of Thailand (EGAT) cohort. Two polymorphisms, that is, rs2248690 in the alpha2-Hereman-Schmid glycoprotein (AHSG) gene and rs9939609 in the fat mass and obesity-Associated (FTO) gene were genotyped. Bidirectional causal models were constructed using a two-stage least-square instrumental variable (IV) regression. First, rs2248690 locus was used as the instrumental variable for the effect of circulating fetuin-A on BMI, and then, the FTO rs9939609 locus was used as the instrumental variable for the effect of BMI on circulating fetuin-A. Results Among the 2558 subjects, the prevalence of the minor AHSG (T) and FTO (A) alleles was 17·9% and 22·1%, respectively. The AHSG rs2248690 locus was highly related to serum fetuin-A levels (P < 0·001). Likewise, the FTO rs9939609 locus and BMI were highly associated (P < 0·001). Mendelian randomization analyses showed that circulating fetuin-A, instrumented by the AHSG rs2248690 locus, was associated with BMI (coefficient = 2·26; 95% CI: 0·39, 4·12). In contrast, BMI, instrumented by the FTO rs9939609 locus, was not associated with circulating fetuin-A (coefficient = 0·0007; 95% CI: -0·0242, 0·0256). Conclusion Our findings suggest a causal association leading from circulating fetuin-A to BMI. There was no evidence of reverse causality from BMI to fetuin-A. © 2013 John Wiley & Sons Ltd.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84899659664&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/34767
ISSN: 13652265
03000664
Appears in Collections:Scopus 2011-2015

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