原创力文档serum uric acid and adiposity deciphering causality using a bidirectional mendelian randomization approach血清尿酸和肥胖解密使用双向因果关系孟德尔随机化的方法.pdfVIP
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serum uric acid and adiposity deciphering causality using a bidirectional mendelian randomization approach血清尿酸和肥胖解密使用双向因果关系孟德尔随机化的方法
Serum Uric Acid and Adiposity: Deciphering Causality
Using a Bidirectional Mendelian Randomization
Approach
1 1 1 1 ´ 2
Tanica Lyngdoh , Philippe Vuistiner , Pedro Marques-Vidal , Valentin Rousson , Gerard Waeber ,
2 1
Peter Vollenweider , Murielle Bochud *
1 Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland, 2 Department of Medicine, Internal Medicine, CHUV, Lausanne,
Switzerland
Abstract
Background: Although the relationship between serum uric acid (SUA) and adiposity is well established, the direction of the
causality is still unclear in the presence of conflicting evidences. We used a bidirectional Mendelian randomization approach
to explore the nature and direction of causality between SUA and adiposity in a population-based study of Caucasians aged
35 to 75 years.
Methods and Findings: We used, as instrumental variables, rs6855911 within the SUA gene SLC2A9 in one direction, and
combinations of SNPs within the adiposity genes FTO, MC4R and TMEM18 in the other direction. Adiposity markers included
weight, body mass index, waist circumference and fat mass. We applied a two-stage least squares regression: a regression of
SUA/adiposity markers on our instruments in the first stage and a regression of the response of interest on the fitted values
from the first stage regression in the second stage. SUA explained by the SLC2A9 instrument was not associated to fat mass
(regression coefficient [95% confidence interval]: 0.05 [20.10, 0.19] for fat mass) contrasting with the ordinary least square
estimate (0.37 [0.34, 0.40]). By contrast, fat mass explained by genetic variants of the FTO, MC4R and TMEM18 genes was
positively
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