Assessment of dried blood spots for DNA methylation profiling

Rosie M Walker; Louise MacGillivray; Sarah McCafferty; Nicola Wrobel; Lee Murphy; Shona M Kerr; Stewart W Morris; Archie Campbell; Andrew M McIntosh; David J Porteous; Kathryn L Evans

doi:10.12688/wellcomeopenres.15136.1

Assessment of dried blood spots for DNA methylation profiling

Wellcome Open Res. 2019 Mar 6:4:44. doi: 10.12688/wellcomeopenres.15136.1. eCollection 2019.

Authors

Rosie M Walker^{1

2}, Louise MacGillivray³, Sarah McCafferty³, Nicola Wrobel³, Lee Murphy³, Shona M Kerr^{1

4}, Stewart W Morris¹, Archie Campbell⁵, Andrew M McIntosh^{2

6}, David J Porteous^#^{1

2

5}, Kathryn L Evans^#^{1

2}

Affiliations

¹ Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Midlothian, EH4 2XU, UK.
² Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Midlothian, EH4 2XU, UK.
³ Edinburgh Clinical Research Facility, Western General Hospital, University of Edinburgh, Edinburgh, Midlothian, EH4 2XU, UK.
⁴ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Midlothian, EH4 2XU, UK.
⁵ Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Midlothian, EH4 2XU, UK.
⁶ Division of Psychiatry, University of Edinburgh, Edinburgh, Midlothian, EH4 2XU, UK.

^# Contributed equally.

Abstract

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 (mean r = 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.

Keywords: DBS; DNA methylation; Generation Scotland; Guthrie cards; dried blood spots.

Abstract

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