Imperial College London


Faculty of MedicineSchool of Public Health

Reader in Cardiometabolic Disease Epidemiology



+44 (0)20 7594 3347a.dehghan CV




157Norfolk PlaceSt Mary's Campus






BibTex format

author = {Ligthart, S and Steenaard, RV and Peters, MJ and van, Meurs JB and Sijbrands, EJ and Uitterlinden, AG and Bonder, MJ and BIOS, consortium and Hofman, A and Franco, OH and Dehghan, A},
doi = {10.1007/s00125-016-3872-0},
journal = {Diabetologia},
pages = {998--1006},
title = {Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes.},
url = {},
volume = {59},
year = {2016}

RIS format (EndNote, RefMan)

AB - AIMS/HYPOTHESIS: Tobacco smoking, a risk factor for diabetes, is an established modifier of DNA methylation. We hypothesised that tobacco smoking modifies DNA methylation of genes previously identified for diabetes. METHODS: We annotated CpG sites available on the Illumina Human Methylation 450K array to diabetes genes previously identified by genome-wide association studies (GWAS), and investigated them for an association with smoking by comparing current to never smokers. The discovery study consisted of 630 individuals (Bonferroni-corrected p = 1.4 × 10(-5)), and we sought replication in an independent sample of 674 individuals. The replicated sites were tested for association with nearby genetic variants and gene expression and fasting glucose and insulin levels. RESULTS: We annotated 3,620 CpG sites to the genes identified in the GWAS on type 2 diabetes. Comparing current smokers to never smokers, we found 12 differentially methylated CpG sites, of which five replicated: cg23161492 within ANPEP (p = 1.3 × 10(-12)); cg26963277 (p = 1.2 × 10(-9)), cg01744331 (p = 8.0 × 10(-6)) and cg16556677 (p = 1.2 × 10(-5)) within KCNQ1 and cg03450842 (p = 3.1 × 10(-8)) within ZMIZ1. The effect of smoking on DNA methylation at the replicated CpG sites attenuated after smoking cessation. Increased DNA methylation at cg23161492 was associated with decreased gene expression levels of ANPEP (p = 8.9 × 10(-5)). rs231356-T, which was associated with hypomethylation of cg26963277 (KCNQ1), was associated with a higher odds of diabetes (OR 1.06, p = 1.3 × 10(-5)). Additionally, hypomethylation of cg26963277 was associated with lower fasting insulin levels (p = 0.04). CONCLUSIONS/INTERPRETATION: Tobacco sm
AU - Ligthart,S
AU - Steenaard,RV
AU - Peters,MJ
AU - van,Meurs JB
AU - Sijbrands,EJ
AU - Uitterlinden,AG
AU - Bonder,MJ
AU - BIOS,consortium
AU - Hofman,A
AU - Franco,OH
AU - Dehghan,A
DO - 10.1007/s00125-016-3872-0
EP - 1006
PY - 2016///
SP - 998
TI - Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes.
T2 - Diabetologia
UR -
UR -
UR -
VL - 59
ER -