DNA methylation within imprinting control regions (ICRs) is fundamental for establishing and maintaining non-random mono-allelic expression of certain genes. We recently surveyed DNA methylation levels within four ICRs [H19-ICR, IGF2-DMR, KvDMR and NESPAS-ICR] in whole-blood genomic DNA from 128 MZ- and 128 DZ-twin pairs. Our analyses revealed high intra-domain covariation in methylation status across CpG dinucleotides and emphasised the interaction between epigenetic variation and the underlying genetic sequence in a parent-of-origin fashion. Here, we extend our analysis to conduct a genome-wide screening of single nucleotide polymorphisms (SNPs) underlying both intra-domain covariation and parent-of-origin-dependent genetic effects on methylation status at individual CpG sites located within ICRs. Most significant SNPs found through multiple-trait genome-wide association (MQFAM) included the previously described rs10732516, associated with methylation at the H19-ICR and rs965808, located within an intronic region of the overlapping imprinted genes GNAS and GNAS-AS1, which are imprinted genes regulated by NESPAS-ICR. At the same time, we identified sixteen SNPs potentially acting in-trans across all four . Furthermore, we identified thirteen SNPs displaying parent-of-origin association over individual methylation sites through a family-based test of association (QTDT). In this exploratory study, we show the value and feasibility of using alternative GWAS in the study of the interaction between genetic sequence and epigenetic state within imprinting regulatory domains. Despite the relatively small sample size, a number of novel associated SNPs that potentially exert their effect in either a parent of origin or in a region dependent manner were identified.