Differences in smoking associated DNA methylation patterns in South Asians and Europeans.

Differences in smoking associated DNA methylation patterns in South Asians and Europeans.
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DOI:
10.1186/1868-7083-6-4
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发表时间:
2014-02-03
影响因子:
5.7
通讯作者:
Relton CL
Relton CL
中科院分区:
医学1区
文献类型:
--
作者:
Elliott HR;Tillin T;McArdle WL;Ho K;Duggirala A;Frayling TM;Davey Smith G;Hughes AD;Chaturvedi N;Relton CL

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DNA甲基化与基因组中多个位点的吸烟状况密切相关。研究主要局限于欧洲人,但吸烟人数增加最多的是低收入国家,如印度次大陆。我们确定了南亚人和欧洲人在吸烟相关基因座上是否存在差异,以及吸烟评分,结合所有与吸烟相关的DNA甲基化评分,是否可以区分吸烟者和非吸烟者。Illumina HM450k头芯片阵列对来自Southall And Brent REvisited (SABRE)队列的192个样本进行了分析。吸烟者在18个独特位点的29个CpG位点上发现了差异甲基化。在AHRR位点发现吸烟状况与族群之间的相互作用。非吸烟者DNA甲基化在另外两个位点6p21.33和GNG12上存在种族差异。除了GFI1和MYO1G,这些差异在很大程度上不受细胞组成调整的影响。构建了基于甲基化谱的吸烟评分。目前的吸烟者在欧洲人中有100%的敏感性和97%的特异性,在南亚人中有80%的敏感性和95%的特异性。在单个CpG位点和综合吸烟评分中,发现了种族间的差异。吸烟评分是识别当前真实吸烟行为的一个有价值的工具。解释与吸烟相关的DNA甲基化的种族差异可能为疾病途径提供有价值的线索。
DNA methylation is strongly associated with smoking status at multiple sites across the genome. Studies have largely been restricted to European origin individuals yet the greatest increase in smoking is occurring in low income countries, such as the Indian subcontinent. We determined whether there are differences between South Asians and Europeans in smoking related loci, and if a smoking score, combining all smoking related DNA methylation scores, could differentiate smokers from non-smokers. Illumina HM450k BeadChip arrays were performed on 192 samples from the Southall And Brent REvisited (SABRE) cohort. Differential methylation in smokers was identified in 29 individual CpG sites at 18 unique loci. Interaction between smoking status and ethnic group was identified at the AHRR locus. Ethnic differences in DNA methylation were identified in non-smokers at two further loci, 6p21.33 and GNG12. With the exception of GFI1 and MYO1G these differences were largely unaffected by adjustment for cell composition. A smoking score based on methylation profile was constructed. Current smokers were identified with 100% sensitivity and 97% specificity in Europeans and with 80% sensitivity and 95% specificity in South Asians. Differences in ethnic groups were identified in both single CpG sites and combined smoking score. The smoking score is a valuable tool for identification of true current smoking behaviour. Explanations for ethnic differences in DNA methylation in association with smoking may provide valuable clues to disease pathways.
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