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Epigenetic signatures of internal migration in Italy.

Campanella G, Polidoro S, Di Gaetano C, Fiorito G, Guarrera S, Krogh V, Palli D, Panico S, Sacerdote C, Tumino R, Elliott P, Matullo G, Chadeau-Hyam M, Vineis P - Int J Epidemiol (2014)

Bottom Line: Using genome-wide DNA methylation profiles from more than 1000 Italian participants, we conducted an epigenome-wide association study (EWAS) to identify differences between south-to-north migrants and their origin (southern natives) and host (north-western natives) populations.We identified several differentially methylated CpG loci, in particular when comparing south-to-north migrants with north-western natives.Our study is the first large agnostic investigation of DNA methylation changes linked to migratory processes, and shows the potential of EWAS to investigate their biological effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Biostatistics, Imperial College London, London, UK,Human Genetics Foundation (HuGeF), Turin, Italy, Department of Medical Sciences, University of Turin, Turin, Italy, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy, Istituto per lo Studio e la Prevenzione Oncologica (ISPO Toscana), Florence, Italy, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy, Piedmont Reference Centre for Epidemiology and Cancer Prevention (CPO Piemonte), Turin, Italy Cancer Registry and Histopathology Unit, Azienda Ospedaliera 'Civile - M. P. Arezzo', Ragusa, Italy and MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.

No MeSH data available.


Related in: MedlinePlus

PCA of DNA methylation levels assayed in the pericentric region on the long arm of chromosome 7: (A) scree plot; (B) Manhattan plot for the association of PCs with migrant status (Kruskal–Wallis rank sum test); (C) box-and-whisker plot for PCs associated with migrant status (P < 0.05) after adjustment for dietary and lifestyle factors.
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dyu198-F3: PCA of DNA methylation levels assayed in the pericentric region on the long arm of chromosome 7: (A) scree plot; (B) Manhattan plot for the association of PCs with migrant status (Kruskal–Wallis rank sum test); (C) box-and-whisker plot for PCs associated with migrant status (P < 0.05) after adjustment for dietary and lifestyle factors.

Mentions: Comparison of south-to-north migrants with respect to the host population (north-western natives) revealed 91 differentially methylated CpG loci (Figure 1B). After removal of 23 candidates whose associated probe sequences could not be uniquely aligned to the reference human genome, and of 33 candidates in the proximity of non-rare genetic variations, 35 CpG loci were left for further consideration, and 22 survived the adjustment for dietary and lifestyle factors. Of these, 17 were found to be relatively hypermethylated in south-to-north migrants, and seven were found in the pericentric region on the long arm of chromosome 7 (from the centromere to 6.37 × 107 bp). These loci exhibited a consistent decreasing gradient from south-to-north migrants to southern natives to north-western natives (Figure 2). They were also flanked by several other loci that shared the same direction of association. This region was additionally characterized by PCA of DNA methylation measurements at 43 enclosed CpG loci assayed by the HM450 platform (filtered according to the criteria described above), before and after adjustment for dietary and lifestyle factors. Irrespective of adjustment, the first principal component explained approximately 35% of the variance (Figure 3A), and was the only component explaining more than 10% of the variance. The association of each principal component with migratory status was formally assessed using Kruskal–Wallis rank sum tests. Results were comparable before and after adjustment; however, the second, third and 36th principal components lost statistical significance after adjustment (Figure 3B). The first principal component was consistently associated with migratory status (P-values 1.71 × 10−8 and 6.28 × 10−6 before and after adjustment, respectively), as was the 15th (P-values 0.043 and 0.041, respectively). Scores exhibited a decreasing gradient similar to that observed in Figure 2, albeit less markedly for the 15th principal component (Figure 3C).Figure 2.


Epigenetic signatures of internal migration in Italy.

Campanella G, Polidoro S, Di Gaetano C, Fiorito G, Guarrera S, Krogh V, Palli D, Panico S, Sacerdote C, Tumino R, Elliott P, Matullo G, Chadeau-Hyam M, Vineis P - Int J Epidemiol (2014)

PCA of DNA methylation levels assayed in the pericentric region on the long arm of chromosome 7: (A) scree plot; (B) Manhattan plot for the association of PCs with migrant status (Kruskal–Wallis rank sum test); (C) box-and-whisker plot for PCs associated with migrant status (P < 0.05) after adjustment for dietary and lifestyle factors.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588856&req=5

dyu198-F3: PCA of DNA methylation levels assayed in the pericentric region on the long arm of chromosome 7: (A) scree plot; (B) Manhattan plot for the association of PCs with migrant status (Kruskal–Wallis rank sum test); (C) box-and-whisker plot for PCs associated with migrant status (P < 0.05) after adjustment for dietary and lifestyle factors.
Mentions: Comparison of south-to-north migrants with respect to the host population (north-western natives) revealed 91 differentially methylated CpG loci (Figure 1B). After removal of 23 candidates whose associated probe sequences could not be uniquely aligned to the reference human genome, and of 33 candidates in the proximity of non-rare genetic variations, 35 CpG loci were left for further consideration, and 22 survived the adjustment for dietary and lifestyle factors. Of these, 17 were found to be relatively hypermethylated in south-to-north migrants, and seven were found in the pericentric region on the long arm of chromosome 7 (from the centromere to 6.37 × 107 bp). These loci exhibited a consistent decreasing gradient from south-to-north migrants to southern natives to north-western natives (Figure 2). They were also flanked by several other loci that shared the same direction of association. This region was additionally characterized by PCA of DNA methylation measurements at 43 enclosed CpG loci assayed by the HM450 platform (filtered according to the criteria described above), before and after adjustment for dietary and lifestyle factors. Irrespective of adjustment, the first principal component explained approximately 35% of the variance (Figure 3A), and was the only component explaining more than 10% of the variance. The association of each principal component with migratory status was formally assessed using Kruskal–Wallis rank sum tests. Results were comparable before and after adjustment; however, the second, third and 36th principal components lost statistical significance after adjustment (Figure 3B). The first principal component was consistently associated with migratory status (P-values 1.71 × 10−8 and 6.28 × 10−6 before and after adjustment, respectively), as was the 15th (P-values 0.043 and 0.041, respectively). Scores exhibited a decreasing gradient similar to that observed in Figure 2, albeit less markedly for the 15th principal component (Figure 3C).Figure 2.

Bottom Line: Using genome-wide DNA methylation profiles from more than 1000 Italian participants, we conducted an epigenome-wide association study (EWAS) to identify differences between south-to-north migrants and their origin (southern natives) and host (north-western natives) populations.We identified several differentially methylated CpG loci, in particular when comparing south-to-north migrants with north-western natives.Our study is the first large agnostic investigation of DNA methylation changes linked to migratory processes, and shows the potential of EWAS to investigate their biological effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Biostatistics, Imperial College London, London, UK,Human Genetics Foundation (HuGeF), Turin, Italy, Department of Medical Sciences, University of Turin, Turin, Italy, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy, Istituto per lo Studio e la Prevenzione Oncologica (ISPO Toscana), Florence, Italy, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy, Piedmont Reference Centre for Epidemiology and Cancer Prevention (CPO Piemonte), Turin, Italy Cancer Registry and Histopathology Unit, Azienda Ospedaliera 'Civile - M. P. Arezzo', Ragusa, Italy and MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.

No MeSH data available.


Related in: MedlinePlus