title: Serum gamma-glutamyl transferase and risk of type 2 diabetes in the general Korean population: a Mendelian randomization study.
abstract: Elevated gamma-glutamyl transferase (GGT) levels are associated with higher risk of type 2 diabetes in observational studies, but the underlying causal relationship is still unclear. Here, we tested a hypothesis that GGT levels have a causal effect on type 2 diabetes risk using Mendelian randomization. Data were collected from 7640 participants in a South Korean population. In a single instrumental variable (IV) analysis using two stage least squares regression with the rs4820599 in the GGT1 gene region as an instrument, one unit of GGT levels (IU/L) was associated with 11% higher risk of type 2 diabetes (odds ratio (OR) = 1.11, 95% confidence interval (CI): 1.04 to 1.19). In a multiple IV analysis using seven genetic variants that have previously been demonstrated to be associated with GGT at a genome-wide level of significance, the corresponding estimate suggested a 2.6% increase in risk (OR = 1.026, 95% CI: 1.001 to 1.052). In a two-sample Mendelian randomization analysis using genetic associations with type 2 diabetes taken from a trans-ethnic GWAS study of 110 452 independent samples, the single IV analysis confirmed an association between the rs4820599 and type 2 diabetes risk (P-value = 0.04); however, the estimate from the multiple IV analysis was compatible with the null (OR = 1.007, 95% CI: 0.993 to 1.022) with considerable heterogeneity between the causal effects estimated using different genetic variants. Overall, there is weak genetic evidence that GGT levels may have a causal role in the development of type 2 diabetes.
authors.affiliation: Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University, Seoul 02841, Republic of Korea.|Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Youn Sue
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Yoonsu
authors.initials: Y
authors.lastname: Cho
authors.affiliation: KoNECT, Korea National Enterprise For Clinical Trials, Seoul 04143, Republic of Korea.|MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Burgess
authors.affiliation: KoNECT, Korea National Enterprise For Clinical Trials, Seoul 04143, Republic of Korea.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: KoNECT, Korea National Enterprise For Clinical Trials, Seoul 04143, Republic of Korea.|Cardiovascular Epidemiology Unit, University of Cambridge, Strangeways Research Laboratory, Wort's Causeway, Cambridge CB1 8RN, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
authors.affiliation: KoNECT, Korea National Enterprise For Clinical Trials, Seoul 04143, Republic of Korea mjshin@korea.ac.kr so-youn.shin@bristol.ac.uk.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University, Seoul 02841, Republic of Korea mjshin@korea.ac.kr so-youn.shin@bristol.ac.uk.|Institute of Genetic Medicine, Newcastle University, Central Pkwy, Newcastle Upon Tyne NE1 3BZ, UK and.
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Shin
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000235:genetics*
chemical_list: D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human