Assessing the causal association between smoking behavior and risk of gout using a Mendelian randomization study

Research output: Contribution to journalArticle

Abstract

This study aimed to examine whether smoking behavior is causally related to gout. Summary statistics of publicly available data from genome-wide association studies (GWAS) of smoking behavior (n = 85,997) served as the exposure dataset, while meta-analysis results of 14 studies including 2115 cases and 67,259 controls of European descent served as the outcome dataset. The data were subjected to two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. Five single-nucleotide polymorphisms (SNPs) from GWAS of smoking behavior were selected as instrumental variables (IVs) to improve inference: CHRNA3 (rs1051730), PDE1C (rs215614), CYP2A6 (rs4105144), CHRNB3 (rs6474412), and CYP2B6 (rs7260329). The IVW data did not support a causal association between smoking behavior and gout (beta = − 0.035, SE = 0.036, p = 0.333). MR-Egger regression indicated that directional pleiotropy did not bias the result (intercept = 0.021; p = 0.560). MR-Egger analysis revealed no causal association between smoking behavior and gout (beta = − 0.074, SE = 0.070, p = 0.366). The weighted median approach did not support a causal association between smoking behavior and gout (beta = − 0.043, SE = 0.040, p = 0.279). Cochran’s Q test indicated no evidence of heterogeneity between IV estimates based on individual variants. The results of “leave one out” analysis demonstrated that no single SNP drove the IVW point estimate. MR estimates using IVW, weighted median, and MR-Egger analysis were consistent and did not support a causal inverse association between smoking behavior and gout.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalClinical Rheumatology
DOIs
Publication statusAccepted/In press - 2018 Jul 12

Fingerprint

Gout
Random Allocation
Risk-Taking
Mendelian Randomization Analysis
Smoking
Genome-Wide Association Study
Single Nucleotide Polymorphism
Meta-Analysis

Keywords

  • Gout
  • Mendelian randomization
  • Smoking

ASJC Scopus subject areas

  • Rheumatology

Cite this

@article{92394fc76242429a9ae3e014e12be1e9,
title = "Assessing the causal association between smoking behavior and risk of gout using a Mendelian randomization study",
abstract = "This study aimed to examine whether smoking behavior is causally related to gout. Summary statistics of publicly available data from genome-wide association studies (GWAS) of smoking behavior (n = 85,997) served as the exposure dataset, while meta-analysis results of 14 studies including 2115 cases and 67,259 controls of European descent served as the outcome dataset. The data were subjected to two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. Five single-nucleotide polymorphisms (SNPs) from GWAS of smoking behavior were selected as instrumental variables (IVs) to improve inference: CHRNA3 (rs1051730), PDE1C (rs215614), CYP2A6 (rs4105144), CHRNB3 (rs6474412), and CYP2B6 (rs7260329). The IVW data did not support a causal association between smoking behavior and gout (beta = − 0.035, SE = 0.036, p = 0.333). MR-Egger regression indicated that directional pleiotropy did not bias the result (intercept = 0.021; p = 0.560). MR-Egger analysis revealed no causal association between smoking behavior and gout (beta = − 0.074, SE = 0.070, p = 0.366). The weighted median approach did not support a causal association between smoking behavior and gout (beta = − 0.043, SE = 0.040, p = 0.279). Cochran’s Q test indicated no evidence of heterogeneity between IV estimates based on individual variants. The results of “leave one out” analysis demonstrated that no single SNP drove the IVW point estimate. MR estimates using IVW, weighted median, and MR-Egger analysis were consistent and did not support a causal inverse association between smoking behavior and gout.",
keywords = "Gout, Mendelian randomization, Smoking",
author = "Lee, {Young Ho}",
year = "2018",
month = "7",
day = "12",
doi = "10.1007/s10067-018-4210-3",
language = "English",
pages = "1--7",
journal = "Clinical Rheumatology",
issn = "0770-3198",
publisher = "Springer London",

}

TY - JOUR

T1 - Assessing the causal association between smoking behavior and risk of gout using a Mendelian randomization study

AU - Lee, Young Ho

PY - 2018/7/12

Y1 - 2018/7/12

N2 - This study aimed to examine whether smoking behavior is causally related to gout. Summary statistics of publicly available data from genome-wide association studies (GWAS) of smoking behavior (n = 85,997) served as the exposure dataset, while meta-analysis results of 14 studies including 2115 cases and 67,259 controls of European descent served as the outcome dataset. The data were subjected to two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. Five single-nucleotide polymorphisms (SNPs) from GWAS of smoking behavior were selected as instrumental variables (IVs) to improve inference: CHRNA3 (rs1051730), PDE1C (rs215614), CYP2A6 (rs4105144), CHRNB3 (rs6474412), and CYP2B6 (rs7260329). The IVW data did not support a causal association between smoking behavior and gout (beta = − 0.035, SE = 0.036, p = 0.333). MR-Egger regression indicated that directional pleiotropy did not bias the result (intercept = 0.021; p = 0.560). MR-Egger analysis revealed no causal association between smoking behavior and gout (beta = − 0.074, SE = 0.070, p = 0.366). The weighted median approach did not support a causal association between smoking behavior and gout (beta = − 0.043, SE = 0.040, p = 0.279). Cochran’s Q test indicated no evidence of heterogeneity between IV estimates based on individual variants. The results of “leave one out” analysis demonstrated that no single SNP drove the IVW point estimate. MR estimates using IVW, weighted median, and MR-Egger analysis were consistent and did not support a causal inverse association between smoking behavior and gout.

AB - This study aimed to examine whether smoking behavior is causally related to gout. Summary statistics of publicly available data from genome-wide association studies (GWAS) of smoking behavior (n = 85,997) served as the exposure dataset, while meta-analysis results of 14 studies including 2115 cases and 67,259 controls of European descent served as the outcome dataset. The data were subjected to two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. Five single-nucleotide polymorphisms (SNPs) from GWAS of smoking behavior were selected as instrumental variables (IVs) to improve inference: CHRNA3 (rs1051730), PDE1C (rs215614), CYP2A6 (rs4105144), CHRNB3 (rs6474412), and CYP2B6 (rs7260329). The IVW data did not support a causal association between smoking behavior and gout (beta = − 0.035, SE = 0.036, p = 0.333). MR-Egger regression indicated that directional pleiotropy did not bias the result (intercept = 0.021; p = 0.560). MR-Egger analysis revealed no causal association between smoking behavior and gout (beta = − 0.074, SE = 0.070, p = 0.366). The weighted median approach did not support a causal association between smoking behavior and gout (beta = − 0.043, SE = 0.040, p = 0.279). Cochran’s Q test indicated no evidence of heterogeneity between IV estimates based on individual variants. The results of “leave one out” analysis demonstrated that no single SNP drove the IVW point estimate. MR estimates using IVW, weighted median, and MR-Egger analysis were consistent and did not support a causal inverse association between smoking behavior and gout.

KW - Gout

KW - Mendelian randomization

KW - Smoking

UR - http://www.scopus.com/inward/record.url?scp=85049782227&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049782227&partnerID=8YFLogxK

U2 - 10.1007/s10067-018-4210-3

DO - 10.1007/s10067-018-4210-3

M3 - Article

SP - 1

EP - 7

JO - Clinical Rheumatology

JF - Clinical Rheumatology

SN - 0770-3198

ER -