Lymphoblastoid cell lines reveal associations of adult DNA methylation with childhood and current adversity that are distinct from whole blood associations.
BACKGROUND
Some cohort studies bank lymphoblastoid cell lines (LCLs) as a renewable source of participant DNA. However, although LCL DNA has proved valuable for genetic studies, its utility in epigenetic epidemiology research is unknown.


METHODS
To assess whether LCL DNA can be used for life-course environmental epigenomics, we carried out a pilot methylomic study (using the Illumina Infinium Human Methylation 450 BeadChip) of nil-passage, Epstein-Barr virus (EBV)-transformed LCLs (n = 42) and 28 matched whole-blood (WB) samples. These were from adult male participants of the British 1958 birth cohort, selected for extremes of social economic position (SEP) in childhood and adulthood, with additional information available on childhood abuse and prenatal tobacco exposure.


RESULTS
We identified a small number of weak associations between these exposures and methylation levels of both individual CpG sites and genomic regions in WB and LCLs. However, only one of the regional, and none of the individual CpG site associations were common to both sample types. The lack of overlap between the associations detected in LCL compared with those found in WB could either be due to the EBV-transformation process, or to the fact that, unlike WB, LCLs are essentially a single (CD19+) cell type. We provide evidence that the latter is the more potent explanation, by showing that CpG sites known to be differentially methylated between different types of blood cell have significantly lower correlations (R = 0.11) than average (R = 0.2) between WB and LCLs in our datasets, whereas sites known to be affected by EBV-transformation have significantly higher correlations (R = 0.3).


CONCLUSIONS
This small pilot study suggests that the DNA methylation profile of LCLs is more closely related to that of B cells than WB and, additionally, that LCLs may nevertheless be useful for life-course environmental epigenomics.
MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol, UK, matthew.suderman@bristol.ac.uk.
Matthew
M
Suderman
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada, Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Jane J
JJ
Pappas
Department of Biochemistry, Faculty of Sciences I, Lebanese University, Beirut, Lebanon.
Nada
N
Borghol
Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
Jessica L
JL
Buxton
School of Social and Community Medicine, University of Bristol, Bristol, UK.
Wendy L
WL
McArdle
MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol, UK.
Susan M
SM
Ring
Human Early Learning Partnership, University of British Columbia, British Columbia, Canada.
Clyde
C
Hertzman
Population, Policy and Practice, UCL Institute of Child Health, London, UK.
Chris
C
Power
Department of Physiology, University of Toronto, Toronto, Ontario, Canada, Sackler Program for Epigenetics & Developmental Psychobiology, McGill University, Montreal, Quebec, Canada and.
Moshe
M
Szyf
Genetics and Epigenetics in Health and Disease Section, UCL Institute of Child Health, UK.
Marcus
M
Pembrey
D000328:Adult; D054523:Adult Survivors of Child Abuse; D001402:B-Lymphocytes / Q000166:cytology*; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012923:Social Class; D064424:Tobacco Use
1958 British Birth Cohort; DNA methylation; Epigenetics; childhood abuse; early-life adversity; lymphoblastoid cell lines; prenatal tobacco; social position