Familial resemblances in blood leukocyte DNA methylation levels.
Epigenetic factors such as DNA methylation are DNA alterations affecting gene expression that can convey environmental information through generations. Only a few studies have demonstrated epigenetic inheritance in humans. Our objective is to quantify genetic and common environmental determinants of familial resemblances in DNA methylation levels, using a family based sample. DNA methylation was measured in 48 French Canadians from 16 families as part of the GENERATION Study. We used the Illumina HumanMethylation450 BeadChip array to measure DNA methylation levels in blood leukocytes on 485,577 CpG sites. Heritability was assessed using the variance components method implemented in the QTDT software, which partitions the variance into polygenic (G), common environmental (C), and non-shared environmental (E) effects. We computed maximal heritability, genetic heritability, and common environmental effect for all probes (12.7%, 8.2%, and 4.5%, respectively) and for statistically significant probes (81.8%, 26.9%, and 54.9%, respectively). Higher maximal heritability was observed in the Major Histocompatibility Complex region on chromosome 6. In conclusion, familial resemblances in DNA methylation levels are mainly attributable to genetic factors when considering the average across the genome, but common environmental effect plays an important role when considering statistically significant probes. Further epigenome-wide studies on larger samples combined with genome-wide genotyping studies are needed to better understand the underlying mechanisms of DNA methylation heritability.
a Institute of Nutrition and Functional Foods (INAF), Laval University , Quebec City , QC , Canada.
Bénédicte L
BL
Tremblay
a Institute of Nutrition and Functional Foods (INAF), Laval University , Quebec City , QC , Canada.
Frédéric
F
Guénard
a Institute of Nutrition and Functional Foods (INAF), Laval University , Quebec City , QC , Canada.
Benoît
B
Lamarche
b CHU de Québec Research Center - Endocrinology and Nephrology , Quebec City , QC , Canada.
Louis
L
Pérusse
a Institute of Nutrition and Functional Foods (INAF), Laval University , Quebec City , QC , Canada.|b CHU de Québec Research Center - Endocrinology and Nephrology , Quebec City , QC , Canada.
Marie-Claude
MC
Vohl
D002170:Canada; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D010375:Pedigree; D014430:Twins, Monozygotic
Blood leukocytes; DNA methylation; familial resemblances; metabolic pathways; microarray