Introduction Several human diseases and conditions,including asthma and allergy,are disproportionally distributed in the world with a significant “Western-developed” vs.“Eastern-developing” gradient.No studies have investigated the molecular framework underlying the differences in asthma and allergy prevalence.Aim We aim to investigate the global influence of Western environments/lifestyles on genome-wide methylation in Chinese immigrants.Methods We compared genome-wide DNA methylation of peripheral blood mononuclear cells in 25 newly arrived Chinese immigrants living in a Western environment for less than 6 months(“Newly arrived”)with 23 Chinese immigrants living in the Western environment for more than two years(“Long-term”)using the Infinium HumanMethylation450 BeadChip.In a sub-group of both subject groups(n=12 each)we also investigated genome-wide gene expression using a Human HT-12 v4 expression beadChip.Results The group average methylation levels of each CpG sites in “Newly arrived” and “Long-term” groups were computed.The percentage of the number of CpG sites with a group mean methylation level in “Long-term” greater than “Newly arrived” was significantly higher than 50%.There were 62.5%probes among the total number of 382,250 valid CpG sites with greater mean Beta(β)in “Long-term” than in “Newly arrived”.In the gene island and promoter areas there were significantly lower percentages of CpG sites where the mean methylation levels in “Long-term” were greater than “Newly arrived” compared to CpG sites in all other gene regions.The global increase of methylation was associated with a general decrease of gene expression in Chinese immigrants living in the Western environment for a longer period of time.Conclusion Chinese immigrants living in Australia for a longer period of time have increased global genome methylation and decreased global gene expression compared with newly arrived immigrants.Our results indicate a global influence of the Western environment on the genome and the relationship of these effects on diseases,including asthma and allergy,requires further study.