Assessment of dried blood spots for DNA methylation profiling

Wellcome Open Research

article

Rosie M. Walker¹  Louise MacGillivray³  Sarah McCafferty³  Nicola Wrobel³  Lee Murphy³  Shona M. Kerr¹  Stewart W. Morris¹  Archie Campbell⁵  Andrew M. McIntosh²  David J. Porteous¹  Kathryn L. Evans¹ 

[1] Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh;Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh;Edinburgh Clinical Research Facility, Western General Hospital, University of Edinburgh;MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh;Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh;Division of Psychiatry, University of Edinburgh

关键词: dried blood spots;    DNA methylation;    DBS;    Guthrie cards;    Generation Scotland;   

DOI  :  10.12688/wellcomeopenres.15136.1

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: DNA methylation reflects health-related environmental exposures and genetic risk, providing insights into aetiological mechanisms and potentially predicting disease onset, progression and treatment response. An increasingly recognised need for large-scale, longitudinally-profiled samples collected world-wide has made the development of efficient and straightforward sample collection and storage procedures a pressing issue. An alternative to the low-temperature storage of EDTA tubes of venous blood samples, which are frequently the source of the DNA used in such studies, is to collect and store at room temperature blood samples using purpose built filter paper, such as Whatman FTA® cards. Our goal was to determine whether DNA stored in this manner can be used to generate DNA methylation profiles comparable to those generated using blood samples frozen in EDTA tubes.Methods: DNA methylation profiles were obtained from matched EDTA tube and Whatman FTA® card whole-blood samples from 62 Generation Scotland: Scottish Family Health Study participants using the Infinium HumanMethylation450 BeadChip. Multiple quality control procedures were implemented, the relationship between the two sample types assessed, and epigenome-wide association studies (EWASs) performed for smoking status, age and the interaction between these variables and sample storage method.Results: Dried blood spot (DBS) DNA methylation profiles were of good quality and DNA methylation profiles from matched DBS and EDTA tube samples were highly correlated (meanr = 0.991) and could distinguish between participants. EWASs replicated established associations for smoking and age, with no evidence for moderation by storage method.Conclusions: Our results support the use of Whatman FTA® cards for collecting and storing blood samples for DNA methylation profiling. This approach is likely to be particularly beneficial for large-scale studies and those carried out in areas where freezer access is limited. Furthermore, our results will inform consideration of the use of newborn heel prick DBSs for research use.

【 授权许可】

CC BY