Table 1 Methods and conclusions from studies of hap-ASM

PBL (6), placenta (3), other normal tissues (7)

MSNP Affy 50 K/250 K; validation by pre-digestion/PCR assays and bis-seq

58 candidate ASM loci identified; 12/16 selected loci independently validated. For a given locus, hap-ASM was seen in 95 to 40% of heterozygotes. ASM in CYP2A7 and VNN1 associated with ASE

[48]

PBL (38)

Targeted bis-seq; validation by HpaII pre-digestion/Seq

ASM found in ~10% of CGIs on Hsa21. For a given locus, ASM was seen in 95 to 13% of heterozygotes; ASM associated with ASE in C21orf81

[182]

LCL (13), PBL (3)

MSNP Affy 500 K; validation by bis-seq

~10% of queried CpGs showed a cis-effect. In some cases, there was a short-range effect of CpG SNPs on methylation at nearby non-polymorphic CpGs

[183]

hESC (3), fibro (4), fibro-reprogrammed iPS cells (5), fibro-derived lymphocytes (3), hESC-fibro hybrid cell (1)

Bis-seq with padlock probes; validation by targeted bis-seq

Non CpG-SNP ASM DMRs were observed in 3–22% of the queried regions; half of these DMRs contained both CpG-SNPs and bona fide ASM. ASM validated in 5/12 selected loci

[59]

PBL (10), buccal cells (10)

MSNP Affy 6.0 array; validation by bis-seq and MS-SNuPE. eQTLs assessed using Affy U133 chips

~1.5% of CpGs showed ASM; 16.3% of the ASM were within 5 kb of a gene that was associated with an eQTL

[184]

PBMC of one individual

WGBS, ASE by TA clone sequencing

599 ASM DMRs with an average size of 312 bp were identified; 5/6 selected genes with haploid DMR(s) within 2 kb of their TSS were associated with ASE

[60]

PBL (8), LCL (1), hESC (1), kidney (1), muscle (1)

RRBS; PCR-based bis-seq validation; RNA-Seq for ASE

~8% of SNPs associated with ASM. ASM regions depleted in CGIs, located in intergenic regions with low evolutionary conservation; enriched in genes with ASE

[61]

PBL (42)

MSNP Affy 6.0 array; validation by bis-seq

Hap-ASM in ~5% of the CpGs; inter-individual variation; multiple hap-ASM SNPs found in LD with GWAS peaks for immune/inflammatory diseases

[63]

Liver (20), brain (13), placenta (20), PMN (5), PBL (22), PBMC (15), lung (7), heart (4), breast epithelial cells (5), sperm (2)

MSNP Affy 250 K and 6.0 arrays; bis-seq for validation and fine-mapping

Mapping of hap-ASM DMRs in STEAP3 and CYP2A7 and imprinted ASM in VTRNA2 and RPN1 showed discrete DMRs precisely overlapping CTCF-binding sites. STEAP3, CYP2A7 and RPN1 show ASE

[51]

PBL (96) from parent–child trios

Bis-seq with padlock probes; Illumina 550 K arrays; Affy 6.0 arrays

Mid-parent offspring, mQTL and ASM analyses revealed cis-acting effects on ~5–14% of the queried CpGs; inter-individual variation in hap-ASM

[185]

Brain (3), T cells (3), liver (2), placenta (2), fetal heart (2), fetal lung (1), macaque PBL and liver (4)

Agilent Methyl-seq, validation by targeted bis-seq and ox-bis-seq

Hap-ASM in ~2% of informative regions; 188 DMRs located near GWAS signals for immune or neuropsychiatric disorders. Hap-ASM DMRs enriched in polymorphic CTCF sites and TFBS. CTCF- and TF-binding likelihood predicts strength and direction of hap-ASM

[49]

145 CD4+ T cells (145), VAT (148), WB (599), monocytes (12), muscle (6)

MCC-seq; WGBS for ASM and mQTL; validation by Illumina 450 K Methyl, genotyping by WGS, Illumina Omni2.5 M, Omni5M; RNA-seq for ASE; ChIP-seq for ASH

Of ~2.2 M queried CpGs, ~32% showed ASM or mQTLs, and ~14% of CpGs showing methylation asymmetry without a genetic basis. 25% and >50% of the instances of ASM and mQTLs, respectively, were tissue-specific. ASM and mQTLs were enriched in enhancers; SNPs linked to ASH were enriched for association with ASM

[53]