Impact of SNPs on methylation readouts by Illumina Infinium HumanMethylation450 BeadChip Array: implications for comparative population studies

BMC Genomics

Research Article

Jadwiga Żebracka-Gala¹  Dagmara Rusinek¹  Aleksandra Pfeifer¹  Barbara Jarząb¹  Patrycja Daca-Roszak²  Ewa Ziętkiewicz²  Michał Witt³  Aleksandra Szybińska⁴ 

[1] Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland;Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland;Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland;International Institute of Molecular and Cell Biology, Warsaw, Poland;International Institute of Molecular and Cell Biology, Warsaw, Poland;

关键词: Human DNA methylation;    Genomic SNPs;    CpG sites;    β-values distribution;    Allele frequency;    Illumina platform;    Infinium probes;   

DOI  :  10.1186/s12864-015-2202-0

 received in 2015-05-20, accepted in 2015-11-11,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundInfinium HumanMethylation 450 BeadChip Arrays by Illumina (Illumina HM450K) are among the most popular CpG microarray platforms widely used in biological and medical research. Several recent studies highlighted the potentially confounding impact of the genomic variation on the results of methylation studies performed using Illumina’s Infinium methylation probes. However, the complexity of SNPs impact on the methylation level measurements (β values) has not been comprehensively described.ResultsIn our comparative study of European and Asian populations performed using Illumina HM450K, we found that the majority of Infinium probes, which differentiated two examined groups, had SNPs in their target sequence. Characteristic tri-modal or bi-modal patterns of β values distribution among individual samples were observed for CpGs with SNPs in the first and second position, respectively. To better understand how SNPs affect methylation readouts, we investigated their impact in the context of SNP position and type, and of the Illumina probe type (Infinium I or II).ConclusionsOur study clearly demonstrates that SNP variation existing in the genome, if not accounted for, may lead to false interpretation of the methylation signal differences suggested by some of the Illumina Infinium probes. In addition, it provides important practical clues for discriminating between differences due to the methylation status and to the genomic polymorphisms, based on the inspection of methylation readouts in individual samples. This approach is of special importance when Illumina Infinium assay is used for any comparative population studies, whether related to cancer, disease, ethnicity where SNP frequencies differentiate the studied groups.

【 授权许可】

CC BY   
© Daca-Roszak et al. 2015